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1406.7123
Ivan Gregor
I. Gregor, J. Dr\"oge, M. Schirmer, C. Quince, A. C. McHardy
PhyloPythiaS+: A self-training method for the rapid reconstruction of low-ranking taxonomic bins from metagenomes
null
null
null
null
q-bio.QM
http://creativecommons.org/licenses/by-nc-sa/3.0/
Metagenomics is an approach for characterizing environmental microbial communities in situ, it allows their functional and taxonomic characterization and to recover sequences from uncultured taxa. For communities of up to medium diversity, e.g. excluding environments such as soil, this is often achieved by a combination of sequence assembly and binning, where sequences are grouped into 'bins' representing taxa of the underlying microbial community from which they originate. Assignment to low-ranking taxonomic bins is an important challenge for binning methods as is scalability to Gb-sized datasets generated with deep sequencing techniques. One of the best available methods for the recovery of species bins from an individual metagenome sample is the expert-trained PhyloPythiaS package, where a human expert decides on the taxa to incorporate in a composition-based taxonomic metagenome classifier and identifies the 'training' sequences using marker genes directly from the sample. Due to the manual effort involved, this approach does not scale to multiple metagenome samples and requires substantial expertise, which researchers who are new to the area may not have. With these challenges in mind, we have developed PhyloPythiaS+, a successor to our previously described method PhyloPythia(S). The newly developed + component performs the work previously done by the human expert. PhyloPythiaS+ also includes a new k-mer counting algorithm, which accelerated k-mer counting 100-fold and reduced the overall execution time of the software by a factor of three. Our software allows to analyze Gb-sized metagenomes with inexpensive hardware, and to recover species or genera-level bins with low error rates in a fully automated fashion.
[ { "created": "Fri, 27 Jun 2014 09:32:48 GMT", "version": "v1" } ]
2014-06-30
[ [ "Gregor", "I.", "" ], [ "Dröge", "J.", "" ], [ "Schirmer", "M.", "" ], [ "Quince", "C.", "" ], [ "McHardy", "A. C.", "" ] ]
Metagenomics is an approach for characterizing environmental microbial communities in situ, it allows their functional and taxonomic characterization and to recover sequences from uncultured taxa. For communities of up to medium diversity, e.g. excluding environments such as soil, this is often achieved by a combination of sequence assembly and binning, where sequences are grouped into 'bins' representing taxa of the underlying microbial community from which they originate. Assignment to low-ranking taxonomic bins is an important challenge for binning methods as is scalability to Gb-sized datasets generated with deep sequencing techniques. One of the best available methods for the recovery of species bins from an individual metagenome sample is the expert-trained PhyloPythiaS package, where a human expert decides on the taxa to incorporate in a composition-based taxonomic metagenome classifier and identifies the 'training' sequences using marker genes directly from the sample. Due to the manual effort involved, this approach does not scale to multiple metagenome samples and requires substantial expertise, which researchers who are new to the area may not have. With these challenges in mind, we have developed PhyloPythiaS+, a successor to our previously described method PhyloPythia(S). The newly developed + component performs the work previously done by the human expert. PhyloPythiaS+ also includes a new k-mer counting algorithm, which accelerated k-mer counting 100-fold and reduced the overall execution time of the software by a factor of three. Our software allows to analyze Gb-sized metagenomes with inexpensive hardware, and to recover species or genera-level bins with low error rates in a fully automated fashion.
1101.4984
James F. Glazebrook PhD
James F. Glazebrook, Rodrick Wallace
Rate distortion coevolutionary dynamics and the flow nature of cognitive epigenetic systems
22 pages
null
null
null
q-bio.OT
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We outline a model for a cognitive epigenetic system based on elements of the Shannon theory of information and the statistical physics of the generalized Onsager relations. Particular attention is paid to the concept of the rate distortion function and from another direction as motivated by the thermodynamics of computing, the fundamental homology with the free energy density of a physical system. A unifying aspect of the dynamic framework involves the concept of a groupoid and of a groupoid atlas. From a stochastic differential equation we postulate a multidimensional Ito process for an epigenetic system from which a stochastic flow may permeate through components of this atlas.
[ { "created": "Wed, 26 Jan 2011 01:49:26 GMT", "version": "v1" } ]
2011-01-27
[ [ "Glazebrook", "James F.", "" ], [ "Wallace", "Rodrick", "" ] ]
We outline a model for a cognitive epigenetic system based on elements of the Shannon theory of information and the statistical physics of the generalized Onsager relations. Particular attention is paid to the concept of the rate distortion function and from another direction as motivated by the thermodynamics of computing, the fundamental homology with the free energy density of a physical system. A unifying aspect of the dynamic framework involves the concept of a groupoid and of a groupoid atlas. From a stochastic differential equation we postulate a multidimensional Ito process for an epigenetic system from which a stochastic flow may permeate through components of this atlas.
0705.2710
Danielle Rojas-Rousse
Danielle Rojas-Rousse (IRBII), Karine Poitrineau, Cesar Basso
The potential of mass rearing of Monoksa dorsiplana (Pteromalidae) a native gregarious ectoparasitoid of Pseudopachymeria spinipes (Bruchidae)in South America
null
Biological Control 41 (30/04/2007) 348-353
null
null
q-bio.PE
null
In Chile and Uruguay,the gregarious Pteromalidae (Monoksa dorsiplana) has been discovered emerging from seeds of the persistent pods of Acacia caven attacked by the univoltin bruchid Pseudopachymeria spinipes. We investigated the potential for mass rearing of this gregarious ectoparasitoid on an alternative bruchid host, Callosobruchus maculatus, to use it against the bruchidae of native and cultured species of Leguminosea seeds in South America. The mass rearing of M.dorsiplana was carried out in a population cage where the density of egg-laying females per infested seed was increased from 1:1 on the first day to 5:1 on the last (fifth) day. Under these experimental conditions egg-clutch size per host increased, and at the same time the mortality of eggs laid also increased. The density of egg-laying females influenced the sex ratio which tended towards a balance of sons and daughters,in contrast to the sex ratio of a single egg-laying female per host (1 son to 7 daughters). The mean weight of adults emerging from a parasitized host was negatively correlated with the egg-clutch size, i.e., as egg-clutch size increased, adult weight decreased. All these results show that mass rearing of the gregarious ectoparasitoid M.dorsiplana was possible under laboratory conditions on an alternative bruchid host C.maculatus. As M.dorsiplana is a natural enemy of larval and pupal stages of bruchidae, the next step was to investigate whether the biological control of bruchid C.maculatus was possible in an experimental structure of stored beans.
[ { "created": "Fri, 18 May 2007 14:29:40 GMT", "version": "v1" } ]
2007-05-23
[ [ "Rojas-Rousse", "Danielle", "", "IRBII" ], [ "Poitrineau", "Karine", "" ], [ "Basso", "Cesar", "" ] ]
In Chile and Uruguay,the gregarious Pteromalidae (Monoksa dorsiplana) has been discovered emerging from seeds of the persistent pods of Acacia caven attacked by the univoltin bruchid Pseudopachymeria spinipes. We investigated the potential for mass rearing of this gregarious ectoparasitoid on an alternative bruchid host, Callosobruchus maculatus, to use it against the bruchidae of native and cultured species of Leguminosea seeds in South America. The mass rearing of M.dorsiplana was carried out in a population cage where the density of egg-laying females per infested seed was increased from 1:1 on the first day to 5:1 on the last (fifth) day. Under these experimental conditions egg-clutch size per host increased, and at the same time the mortality of eggs laid also increased. The density of egg-laying females influenced the sex ratio which tended towards a balance of sons and daughters,in contrast to the sex ratio of a single egg-laying female per host (1 son to 7 daughters). The mean weight of adults emerging from a parasitized host was negatively correlated with the egg-clutch size, i.e., as egg-clutch size increased, adult weight decreased. All these results show that mass rearing of the gregarious ectoparasitoid M.dorsiplana was possible under laboratory conditions on an alternative bruchid host C.maculatus. As M.dorsiplana is a natural enemy of larval and pupal stages of bruchidae, the next step was to investigate whether the biological control of bruchid C.maculatus was possible in an experimental structure of stored beans.
q-bio/0507035
Leonard M. Sander
Thomas Callaghan, Evgeniy Khain, Leonard M. Sander, and Robert M. Ziff
A stochastic model for wound healing
16 pages, 7 figures
null
10.1007/s10955-006-9022-1
null
q-bio.CB
null
We present a discrete stochastic model which represents many of the salient features of the biological process of wound healing. The model describes fronts of cells invading a wound. We have numerical results in one and two dimensions. In one dimension we can give analytic results for the front speed as a power series expansion in a parameter, p, that gives the relative size of proliferation and diffusion processes for the invading cells. In two dimensions the model becomes the Eden model for p near 1. In both one and two dimensions for small p, front propagation for this model should approach that of the Fisher-Kolmogorov equation. However, as in other cases, this discrete model approaches Fisher-Kolmogorov behavior slowly.
[ { "created": "Fri, 22 Jul 2005 16:01:54 GMT", "version": "v1" } ]
2009-11-11
[ [ "Callaghan", "Thomas", "" ], [ "Khain", "Evgeniy", "" ], [ "Sander", "Leonard M.", "" ], [ "Ziff", "Robert M.", "" ] ]
We present a discrete stochastic model which represents many of the salient features of the biological process of wound healing. The model describes fronts of cells invading a wound. We have numerical results in one and two dimensions. In one dimension we can give analytic results for the front speed as a power series expansion in a parameter, p, that gives the relative size of proliferation and diffusion processes for the invading cells. In two dimensions the model becomes the Eden model for p near 1. In both one and two dimensions for small p, front propagation for this model should approach that of the Fisher-Kolmogorov equation. However, as in other cases, this discrete model approaches Fisher-Kolmogorov behavior slowly.
1901.01560
Luca Peliti
Luca Peliti
Evolution and Probability
16 pages, 12 figures, a popular science talk
null
null
null
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Life forms exhibit such a degree of exquisite organization that it seems impossible that they could have developed out of a process of trial and error, as intimated by the theory of Darwinian evolution. In this general public paper I discuss how differential reproduction rates work in producing an exceedingly high degree of improbability, and the conceptual tools of the theory of evolution help us to predict, to some degree, the course of evolution -- as it is routinely done, e.g., in the process leading to the yearly influenza vaccines.
[ { "created": "Sun, 6 Jan 2019 16:01:10 GMT", "version": "v1" } ]
2019-01-08
[ [ "Peliti", "Luca", "" ] ]
Life forms exhibit such a degree of exquisite organization that it seems impossible that they could have developed out of a process of trial and error, as intimated by the theory of Darwinian evolution. In this general public paper I discuss how differential reproduction rates work in producing an exceedingly high degree of improbability, and the conceptual tools of the theory of evolution help us to predict, to some degree, the course of evolution -- as it is routinely done, e.g., in the process leading to the yearly influenza vaccines.
1809.08378
Ryan Renslow
Sean M. Colby, Dennis G. Thomas, Jamie R. Nunez, Douglas J. Baxter, Kurt R. Glaesemann, Joseph M. Brown, Meg A Pirrung, Niranjan Govind, Justin G. Teeguarden, Thomas O. Metz, Ryan S. Renslow
ISiCLE: A molecular collision cross section calculation pipeline for establishing large in silico reference libraries for compound identification
null
null
null
null
q-bio.BM physics.chem-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Comprehensive and confident identifications of metabolites and other chemicals in complex samples will revolutionize our understanding of the role these chemically diverse molecules play in biological systems. Despite recent advances, metabolomics studies still result in the detection of a disproportionate number of features than cannot be confidently assigned to a chemical structure. This inadequacy is driven by the single most significant limitation in metabolomics: the reliance on reference libraries constructed by analysis of authentic reference chemicals. To this end, we have developed the in silico chemical library engine (ISiCLE), a high-performance computing-friendly cheminformatics workflow for generating libraries of chemical properties. In the instantiation described here, we predict probable three-dimensional molecular conformers using chemical identifiers as input, from which collision cross sections (CCS) are derived. The approach employs state-of-the-art first-principles simulation, distinguished by use of molecular dynamics, quantum chemistry, and ion mobility calculations to generate structures and libraries, all without training data. Importantly, optimization of ISiCLE included a refactoring of the popular MOBCAL code for trajectory-based mobility calculations, improving its computational efficiency by over two orders of magnitude. Calculated CCS values were validated against 1,983 experimentally-measured CCS values and compared to previously reported CCS calculation approaches. An online database is introduced for sharing both calculated and experimental CCS values (metabolomics.pnnl.gov), initially including a CCS library with over 1 million entries. Finally, three successful applications of molecule characterization using calculated CCS are described. This work represents a promising method to address the limitations of small molecule identification.
[ { "created": "Sat, 22 Sep 2018 03:46:56 GMT", "version": "v1" } ]
2018-09-25
[ [ "Colby", "Sean M.", "" ], [ "Thomas", "Dennis G.", "" ], [ "Nunez", "Jamie R.", "" ], [ "Baxter", "Douglas J.", "" ], [ "Glaesemann", "Kurt R.", "" ], [ "Brown", "Joseph M.", "" ], [ "Pirrung", "Meg A", "" ], [ "Govind", "Niranjan", "" ], [ "Teeguarden", "Justin G.", "" ], [ "Metz", "Thomas O.", "" ], [ "Renslow", "Ryan S.", "" ] ]
Comprehensive and confident identifications of metabolites and other chemicals in complex samples will revolutionize our understanding of the role these chemically diverse molecules play in biological systems. Despite recent advances, metabolomics studies still result in the detection of a disproportionate number of features than cannot be confidently assigned to a chemical structure. This inadequacy is driven by the single most significant limitation in metabolomics: the reliance on reference libraries constructed by analysis of authentic reference chemicals. To this end, we have developed the in silico chemical library engine (ISiCLE), a high-performance computing-friendly cheminformatics workflow for generating libraries of chemical properties. In the instantiation described here, we predict probable three-dimensional molecular conformers using chemical identifiers as input, from which collision cross sections (CCS) are derived. The approach employs state-of-the-art first-principles simulation, distinguished by use of molecular dynamics, quantum chemistry, and ion mobility calculations to generate structures and libraries, all without training data. Importantly, optimization of ISiCLE included a refactoring of the popular MOBCAL code for trajectory-based mobility calculations, improving its computational efficiency by over two orders of magnitude. Calculated CCS values were validated against 1,983 experimentally-measured CCS values and compared to previously reported CCS calculation approaches. An online database is introduced for sharing both calculated and experimental CCS values (metabolomics.pnnl.gov), initially including a CCS library with over 1 million entries. Finally, three successful applications of molecule characterization using calculated CCS are described. This work represents a promising method to address the limitations of small molecule identification.
2009.10514
Maxime De Bois
Maxime De Bois, Moun\^im A. El Yacoubi, Mehdi Ammi
Integration of Clinical Criteria into the Training of Deep Models: Application to Glucose Prediction for Diabetic People
null
null
null
null
q-bio.QM cs.LG
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Standard objective functions used during the training of neural-network-based predictive models do not consider clinical criteria, leading to models that are not necessarily clinically acceptable. In this study, we look at this problem from the perspective of the forecasting of future glucose values for diabetic people. In this study, we propose the coherent mean squared glycemic error (gcMSE) loss function. It penalizes the model during its training not only of the prediction errors, but also on the predicted variation errors which is important in glucose prediction. Moreover, it makes possible to adjust the weighting of the different areas in the error space to better focus on dangerous regions. In order to use the loss function in practice, we propose an algorithm that progressively improves the clinical acceptability of the model, so that we can achieve the best tradeoff possible between accuracy and given clinical criteria. We evaluate the approaches using two diabetes datasets, one having type-1 patients and the other type-2 patients. The results show that using the gcMSE loss function, instead of a standard MSE loss function, improves the clinical acceptability of the models. In particular, the improvements are significant in the hypoglycemia region. We also show that this increased clinical acceptability comes at the cost of a decrease in the average accuracy of the model. Finally, we show that this tradeoff between accuracy and clinical acceptability can be successfully addressed with the proposed algorithm. For given clinical criteria, the algorithm can find the optimal solution that maximizes the accuracy while at the same meeting the criteria.
[ { "created": "Mon, 21 Sep 2020 15:05:28 GMT", "version": "v1" }, { "created": "Wed, 23 Sep 2020 08:05:47 GMT", "version": "v2" } ]
2020-09-24
[ [ "De Bois", "Maxime", "" ], [ "Yacoubi", "Mounîm A. El", "" ], [ "Ammi", "Mehdi", "" ] ]
Standard objective functions used during the training of neural-network-based predictive models do not consider clinical criteria, leading to models that are not necessarily clinically acceptable. In this study, we look at this problem from the perspective of the forecasting of future glucose values for diabetic people. In this study, we propose the coherent mean squared glycemic error (gcMSE) loss function. It penalizes the model during its training not only of the prediction errors, but also on the predicted variation errors which is important in glucose prediction. Moreover, it makes possible to adjust the weighting of the different areas in the error space to better focus on dangerous regions. In order to use the loss function in practice, we propose an algorithm that progressively improves the clinical acceptability of the model, so that we can achieve the best tradeoff possible between accuracy and given clinical criteria. We evaluate the approaches using two diabetes datasets, one having type-1 patients and the other type-2 patients. The results show that using the gcMSE loss function, instead of a standard MSE loss function, improves the clinical acceptability of the models. In particular, the improvements are significant in the hypoglycemia region. We also show that this increased clinical acceptability comes at the cost of a decrease in the average accuracy of the model. Finally, we show that this tradeoff between accuracy and clinical acceptability can be successfully addressed with the proposed algorithm. For given clinical criteria, the algorithm can find the optimal solution that maximizes the accuracy while at the same meeting the criteria.
1509.07440
Denis Michel
Denis Michel
A role for ATP-dependent chromatin remodeling in the hierarchical cooperativity between noninteracting transcription factors
12 pages, 4 figures. This manuscript is an extended version of the article: Hierarchical cooperativity mediated by chromatin remodeling; the model of the MMTV transcription regulation. 2011. J. Theor. Biol. 287, 74-81
J. Theor. Biol. 287, 74-81 (2011)
10.1016/j.jtbi.2011.07.020
null
q-bio.MN
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Chromatin remodeling machineries are abundant and diverse in eukaryotic cells. They have been involved in a variety of situations such as histone exchange and DNA repair, but their importance in gene expression remains unclear. Although the influence of nucleosome position on the regulation of gene expression is generally envisioned under the quasi-equilibrium perspective, it is proposed that given the ATP-dependence of chromatin remodeling enzymes, certain mechanisms necessitate non-equilibrium treatments. Examination of the celebrated chromatin remodeling system of the mouse mammary tumor virus, in which the binding of transcription factors opens the way to other ones, reveals that breaking equilibrium offers a subtle mode of transcription factor cooperativity, avoids molecular trapping phenomena and allows to reconcile previously conflicting experimental data. This mechanism provides a control lever of promoter responsiveness to transcription factor combinations, challenging the classical view of the unilateral influence of pioneer on secondary transcription factors.
[ { "created": "Thu, 24 Sep 2015 17:14:07 GMT", "version": "v1" } ]
2015-09-25
[ [ "Michel", "Denis", "" ] ]
Chromatin remodeling machineries are abundant and diverse in eukaryotic cells. They have been involved in a variety of situations such as histone exchange and DNA repair, but their importance in gene expression remains unclear. Although the influence of nucleosome position on the regulation of gene expression is generally envisioned under the quasi-equilibrium perspective, it is proposed that given the ATP-dependence of chromatin remodeling enzymes, certain mechanisms necessitate non-equilibrium treatments. Examination of the celebrated chromatin remodeling system of the mouse mammary tumor virus, in which the binding of transcription factors opens the way to other ones, reveals that breaking equilibrium offers a subtle mode of transcription factor cooperativity, avoids molecular trapping phenomena and allows to reconcile previously conflicting experimental data. This mechanism provides a control lever of promoter responsiveness to transcription factor combinations, challenging the classical view of the unilateral influence of pioneer on secondary transcription factors.
0708.1865
Pan-Jun Kim
Pan-Jun Kim, Dong-Yup Lee, Tae Yong Kim, Kwang Ho Lee, Hawoong Jeong, Sang Yup Lee, Sunwon Park
Metabolite essentiality elucidates robustness of Escherichia coli metabolism
Supplements available at http://stat.kaist.ac.kr/publication/2007/PJKim_pnas_supplement.pdf
Proc. Natl. Acad. Sci. USA. 104 13638 (2007)
10.1073/pnas.0703262104
null
q-bio.MN physics.bio-ph q-bio.QM
null
Complex biological systems are very robust to genetic and environmental changes at all levels of organization. Many biological functions of Escherichia coli metabolism can be sustained against single-gene or even multiple-gene mutations by using redundant or alternative pathways. Thus, only a limited number of genes have been identified to be lethal to the cell. In this regard, the reaction-centric gene deletion study has a limitation in understanding the metabolic robustness. Here, we report the use of flux-sum, which is the summation of all incoming or outgoing fluxes around a particular metabolite under pseudo-steady state conditions, as a good conserved property for elucidating such robustness of E. coli from the metabolite point of view. The functional behavior, as well as the structural and evolutionary properties of metabolites essential to the cell survival, was investigated by means of a constraints-based flux analysis under perturbed conditions. The essential metabolites are capable of maintaining a steady flux-sum even against severe perturbation by actively redistributing the relevant fluxes. Disrupting the flux-sum maintenance was found to suppress cell growth. This approach of analyzing metabolite essentiality provides insight into cellular robustness and concomitant fragility, which can be used for several applications, including the development of new drugs for treating pathogens.
[ { "created": "Tue, 14 Aug 2007 11:38:00 GMT", "version": "v1" } ]
2007-08-30
[ [ "Kim", "Pan-Jun", "" ], [ "Lee", "Dong-Yup", "" ], [ "Kim", "Tae Yong", "" ], [ "Lee", "Kwang Ho", "" ], [ "Jeong", "Hawoong", "" ], [ "Lee", "Sang Yup", "" ], [ "Park", "Sunwon", "" ] ]
Complex biological systems are very robust to genetic and environmental changes at all levels of organization. Many biological functions of Escherichia coli metabolism can be sustained against single-gene or even multiple-gene mutations by using redundant or alternative pathways. Thus, only a limited number of genes have been identified to be lethal to the cell. In this regard, the reaction-centric gene deletion study has a limitation in understanding the metabolic robustness. Here, we report the use of flux-sum, which is the summation of all incoming or outgoing fluxes around a particular metabolite under pseudo-steady state conditions, as a good conserved property for elucidating such robustness of E. coli from the metabolite point of view. The functional behavior, as well as the structural and evolutionary properties of metabolites essential to the cell survival, was investigated by means of a constraints-based flux analysis under perturbed conditions. The essential metabolites are capable of maintaining a steady flux-sum even against severe perturbation by actively redistributing the relevant fluxes. Disrupting the flux-sum maintenance was found to suppress cell growth. This approach of analyzing metabolite essentiality provides insight into cellular robustness and concomitant fragility, which can be used for several applications, including the development of new drugs for treating pathogens.
1908.07048
Jinzhi Lei
Jinzhi Lei
Evolutionary dynamics of cancer: from epigenetic regulation to cell population dynamics -- mathematical model framework, applications, and open problems
19 pages, 3 figures
null
10.1007/s11425-019-1629-7
null
q-bio.CB
http://creativecommons.org/licenses/by-nc-sa/4.0/
Predictive modeling of the evolutionary dynamics of cancer is a challenge issue in computational cancer biology. In this paper, we propose a general mathematical model framework for the evolutionary dynamics of cancer with plasticity and heterogeneity in cancer cells. Cancer is a group of diseases involving abnormal cell growth, during which abnormal regulations in stem cell regeneration are essential for the dynamics of cancer development. In general, the dynamics of stem cell regeneration can be simplified as a $\mathrm{G_0}$ phase cell cycle model, which lead to a delay differentiation equation. When cell heterogeneity and plasticity are considered, we establish a differential-integral equation based on the random transition of epigenetic states of stem cells during cell division. The proposed model highlights cell heterogeneity and plasticity, and connects the heterogeneity with cell-to-cell variance in cellular behaviors, e.g. proliferation, apoptosis, and differentiation/senescence, and can be extended to include gene mutation-induced tumor development. Hybrid computations models are developed based on the mathematical model framework, and are applied to the process of inflammation-induced tumorigenesis and tumor relapse after CAR-T therapy. Finally, we give rise to several mathematical problems related to the proposed differential-integral equation. Answers to these problems are crucial for the understanding of the evolutionary dynamics of cancer.
[ { "created": "Mon, 19 Aug 2019 19:54:29 GMT", "version": "v1" } ]
2020-01-10
[ [ "Lei", "Jinzhi", "" ] ]
Predictive modeling of the evolutionary dynamics of cancer is a challenge issue in computational cancer biology. In this paper, we propose a general mathematical model framework for the evolutionary dynamics of cancer with plasticity and heterogeneity in cancer cells. Cancer is a group of diseases involving abnormal cell growth, during which abnormal regulations in stem cell regeneration are essential for the dynamics of cancer development. In general, the dynamics of stem cell regeneration can be simplified as a $\mathrm{G_0}$ phase cell cycle model, which lead to a delay differentiation equation. When cell heterogeneity and plasticity are considered, we establish a differential-integral equation based on the random transition of epigenetic states of stem cells during cell division. The proposed model highlights cell heterogeneity and plasticity, and connects the heterogeneity with cell-to-cell variance in cellular behaviors, e.g. proliferation, apoptosis, and differentiation/senescence, and can be extended to include gene mutation-induced tumor development. Hybrid computations models are developed based on the mathematical model framework, and are applied to the process of inflammation-induced tumorigenesis and tumor relapse after CAR-T therapy. Finally, we give rise to several mathematical problems related to the proposed differential-integral equation. Answers to these problems are crucial for the understanding of the evolutionary dynamics of cancer.
2108.13661
Eric Bonnet
Eric Bonnet
Using convolutional neural networks for the classification of breast cancer images
13 pages, 4 figures, 4 tables; corrected typos; added an additional breast carcinoma image dataset; added a total of twelve CNN models tested. Additional testing for transfer learning and complexity of the models
null
null
null
q-bio.QM eess.IV
http://creativecommons.org/licenses/by/4.0/
An important part of breast cancer staging is the assessment of the sentinel axillary node for early signs of tumor spreading. However, this assessment by pathologists is not always easy and retrospective surveys often requalify the status of a high proportion of sentinel nodes. Convolutional Neural Networks (CNNs) are a class of deep learning algorithms that have shown excellent performances in the most challenging visual classification tasks, with numerous applications in medical imaging. In this study I compare twelve different CNNs and different hardware acceleration devices for the detection of breast cancer from microscopic images of breast cancer tissue. Convolutional models are trained and tested on two public datasets. The first one is composed of more than 300,000 images of sentinel lymph node tissue from breast cancer patients, while the second one has more than 220,000 images from inductive breast carcinoma tissue, one of the most common forms of breast cancer. Four different hardware acceleration cards were used, with an off-the-shelf deep learning framework. The impact of transfer learning and hyperparameters fine-tuning are tested. Hardware acceleration device performance can improve training time by a factor of five to twelve, depending on the model used. On the other hand, increasing convolutional depth will augment the training time by a factor of four to six times, depending on the acceleration device used. Increasing the depth and the complexity of the model generally improves performance, but the relationship is not linear and also depends on the architecture of the model. The performance of transfer learning is always worse compared to a complete retraining of the model. Fine-tuning the hyperparameters of the model improves the results, with the best model showing a performance comparable to state-of-the-art models.
[ { "created": "Tue, 31 Aug 2021 07:53:41 GMT", "version": "v1" }, { "created": "Thu, 27 Oct 2022 14:15:20 GMT", "version": "v2" }, { "created": "Mon, 29 Apr 2024 11:53:17 GMT", "version": "v3" } ]
2024-04-30
[ [ "Bonnet", "Eric", "" ] ]
An important part of breast cancer staging is the assessment of the sentinel axillary node for early signs of tumor spreading. However, this assessment by pathologists is not always easy and retrospective surveys often requalify the status of a high proportion of sentinel nodes. Convolutional Neural Networks (CNNs) are a class of deep learning algorithms that have shown excellent performances in the most challenging visual classification tasks, with numerous applications in medical imaging. In this study I compare twelve different CNNs and different hardware acceleration devices for the detection of breast cancer from microscopic images of breast cancer tissue. Convolutional models are trained and tested on two public datasets. The first one is composed of more than 300,000 images of sentinel lymph node tissue from breast cancer patients, while the second one has more than 220,000 images from inductive breast carcinoma tissue, one of the most common forms of breast cancer. Four different hardware acceleration cards were used, with an off-the-shelf deep learning framework. The impact of transfer learning and hyperparameters fine-tuning are tested. Hardware acceleration device performance can improve training time by a factor of five to twelve, depending on the model used. On the other hand, increasing convolutional depth will augment the training time by a factor of four to six times, depending on the acceleration device used. Increasing the depth and the complexity of the model generally improves performance, but the relationship is not linear and also depends on the architecture of the model. The performance of transfer learning is always worse compared to a complete retraining of the model. Fine-tuning the hyperparameters of the model improves the results, with the best model showing a performance comparable to state-of-the-art models.
2206.07632
Seul Lee
Seul Lee, Jaehyeong Jo, Sung Ju Hwang
Exploring Chemical Space with Score-based Out-of-distribution Generation
ICML 2023
null
null
null
q-bio.BM cs.LG physics.chem-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
A well-known limitation of existing molecular generative models is that the generated molecules highly resemble those in the training set. To generate truly novel molecules that may have even better properties for de novo drug discovery, more powerful exploration in the chemical space is necessary. To this end, we propose Molecular Out-Of-distribution Diffusion(MOOD), a score-based diffusion scheme that incorporates out-of-distribution (OOD) control in the generative stochastic differential equation (SDE) with simple control of a hyperparameter, thus requires no additional costs. Since some novel molecules may not meet the basic requirements of real-world drugs, MOOD performs conditional generation by utilizing the gradients from a property predictor that guides the reverse-time diffusion process to high-scoring regions according to target properties such as protein-ligand interactions, drug-likeness, and synthesizability. This allows MOOD to search for novel and meaningful molecules rather than generating unseen yet trivial ones. We experimentally validate that MOOD is able to explore the chemical space beyond the training distribution, generating molecules that outscore ones found with existing methods, and even the top 0.01% of the original training pool. Our code is available at https://github.com/SeulLee05/MOOD.
[ { "created": "Mon, 6 Jun 2022 06:17:11 GMT", "version": "v1" }, { "created": "Tue, 9 May 2023 10:31:37 GMT", "version": "v2" }, { "created": "Sat, 3 Jun 2023 08:43:39 GMT", "version": "v3" } ]
2023-06-06
[ [ "Lee", "Seul", "" ], [ "Jo", "Jaehyeong", "" ], [ "Hwang", "Sung Ju", "" ] ]
A well-known limitation of existing molecular generative models is that the generated molecules highly resemble those in the training set. To generate truly novel molecules that may have even better properties for de novo drug discovery, more powerful exploration in the chemical space is necessary. To this end, we propose Molecular Out-Of-distribution Diffusion(MOOD), a score-based diffusion scheme that incorporates out-of-distribution (OOD) control in the generative stochastic differential equation (SDE) with simple control of a hyperparameter, thus requires no additional costs. Since some novel molecules may not meet the basic requirements of real-world drugs, MOOD performs conditional generation by utilizing the gradients from a property predictor that guides the reverse-time diffusion process to high-scoring regions according to target properties such as protein-ligand interactions, drug-likeness, and synthesizability. This allows MOOD to search for novel and meaningful molecules rather than generating unseen yet trivial ones. We experimentally validate that MOOD is able to explore the chemical space beyond the training distribution, generating molecules that outscore ones found with existing methods, and even the top 0.01% of the original training pool. Our code is available at https://github.com/SeulLee05/MOOD.
1307.0178
Dan Siegal-Gaskins
Dan Siegal-Gaskins, Vincent Noireaux, and Richard M. Murray
Biomolecular resource utilization in elementary cell-free gene circuits
Accepted to the 2013 American Control Conference
null
null
null
q-bio.MN q-bio.BM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We present a detailed dynamical model of the behavior of transcription-translation circuits in vitro that makes explicit the roles played by essential molecular resources. A set of simple two-gene test circuits operating in a cell-free biochemical 'breadboard' validate this model and highlight the consequences of limited resource availability. In particular, we are able to confirm the existence of biomolecular 'crosstalk' and isolate its individual sources. The implications of crosstalk for biomolecular circuit design and function are discussed.
[ { "created": "Sun, 30 Jun 2013 05:14:12 GMT", "version": "v1" } ]
2013-07-02
[ [ "Siegal-Gaskins", "Dan", "" ], [ "Noireaux", "Vincent", "" ], [ "Murray", "Richard M.", "" ] ]
We present a detailed dynamical model of the behavior of transcription-translation circuits in vitro that makes explicit the roles played by essential molecular resources. A set of simple two-gene test circuits operating in a cell-free biochemical 'breadboard' validate this model and highlight the consequences of limited resource availability. In particular, we are able to confirm the existence of biomolecular 'crosstalk' and isolate its individual sources. The implications of crosstalk for biomolecular circuit design and function are discussed.
1408.6006
Maxim Lavrentovich
Maxim O. Lavrentovich and David R. Nelson
Survival Probabilities at Spherical Frontiers
35 pages, 11 figures, revised version
Theor. Popul. Biol. 102 (2015) 26-39
10.1016/j.tpb.2015.03.002
null
q-bio.PE cond-mat.stat-mech
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Motivated by tumor growth and spatial population genetics, we study the interplay between evolutionary and spatial dynamics at the surfaces of three-dimensional, spherical range expansions. We consider range expansion radii that grow with an arbitrary power-law in time: $R(t)=R_0(1+t/t^*)^{\Theta}$, where $\Theta$ is a growth exponent, $R_0$ is the initial radius, and $t^*$ is a characteristic time for the growth, to be affected by the inflating geometry. We vary the parameters $t^*$ and $\Theta$ to capture a variety of possible growth regimes. Guided by recent results for two-dimensional inflating range expansions, we identify key dimensionless parameters that describe the survival probability of a mutant cell with a small selective advantage arising at the population frontier. Using analytical techniques, we calculate this probability for arbitrary $\Theta$. We compare our results to simulations of linearly inflating expansions ($\Theta=1$ spherical Fisher-Kolmogorov-Petrovsky-Piscunov waves) and treadmilling populations ($\Theta=0$, with cells in the interior removed by apoptosis or a similar process). We find that mutations at linearly inflating fronts have survival probabilities enhanced by factors of 100 or more relative to mutations at treadmilling population frontiers. We also discuss the special properties of "marginally inflating" $(\Theta=1/2)$ expansions.
[ { "created": "Tue, 26 Aug 2014 04:57:36 GMT", "version": "v1" }, { "created": "Mon, 1 Jun 2015 14:59:59 GMT", "version": "v2" } ]
2015-06-02
[ [ "Lavrentovich", "Maxim O.", "" ], [ "Nelson", "David R.", "" ] ]
Motivated by tumor growth and spatial population genetics, we study the interplay between evolutionary and spatial dynamics at the surfaces of three-dimensional, spherical range expansions. We consider range expansion radii that grow with an arbitrary power-law in time: $R(t)=R_0(1+t/t^*)^{\Theta}$, where $\Theta$ is a growth exponent, $R_0$ is the initial radius, and $t^*$ is a characteristic time for the growth, to be affected by the inflating geometry. We vary the parameters $t^*$ and $\Theta$ to capture a variety of possible growth regimes. Guided by recent results for two-dimensional inflating range expansions, we identify key dimensionless parameters that describe the survival probability of a mutant cell with a small selective advantage arising at the population frontier. Using analytical techniques, we calculate this probability for arbitrary $\Theta$. We compare our results to simulations of linearly inflating expansions ($\Theta=1$ spherical Fisher-Kolmogorov-Petrovsky-Piscunov waves) and treadmilling populations ($\Theta=0$, with cells in the interior removed by apoptosis or a similar process). We find that mutations at linearly inflating fronts have survival probabilities enhanced by factors of 100 or more relative to mutations at treadmilling population frontiers. We also discuss the special properties of "marginally inflating" $(\Theta=1/2)$ expansions.
1001.3449
Adrian Melott
A.L. Melott (Kansas) and R.K. Bambach (Museum of Natural History, Smithsonian Institution)
An ubiquitous ~62 Myr periodic fluctuation superimposed on general trends in fossil biodiversity
Summry of comments presented at the North American Paleontological Convention, June 25, 2009
null
null
null
q-bio.PE astro-ph.EP physics.bio-ph physics.geo-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
A 62 Myr periodicity is superimposed on other longer-term trends in fossil biodiversity. This cycle can be discerned in marine data based on the Sepkoski compendium, the Paleobiology Database, and the Fossil Record 2. The signal also exists in changes in sea level/sediment, but is much weaker than in biodiversity itself. A significant excess of 19 previously identified Phanerozoic mass extinctions occur on the declining phase of the 62 Myr cycle. appearance of the signal in sampling-standardized biodiversity data, it is likely not to be a sampling artifact, but either a consequence of sea-level changes or an additional effect of some common cause for them both. In either case, it is intriguing why both changes would have a regular pattern.
[ { "created": "Wed, 20 Jan 2010 03:04:53 GMT", "version": "v1" } ]
2010-01-21
[ [ "Melott", "A. L.", "", "Kansas" ], [ "Bambach", "R. K.", "", "Museum of Natural History,\n Smithsonian Institution" ] ]
A 62 Myr periodicity is superimposed on other longer-term trends in fossil biodiversity. This cycle can be discerned in marine data based on the Sepkoski compendium, the Paleobiology Database, and the Fossil Record 2. The signal also exists in changes in sea level/sediment, but is much weaker than in biodiversity itself. A significant excess of 19 previously identified Phanerozoic mass extinctions occur on the declining phase of the 62 Myr cycle. appearance of the signal in sampling-standardized biodiversity data, it is likely not to be a sampling artifact, but either a consequence of sea-level changes or an additional effect of some common cause for them both. In either case, it is intriguing why both changes would have a regular pattern.
2210.08194
Margaret Cheung
August George, Doo Nam Kim, Trevor Moser, Ian T. Gildea, James E. Evans, Margaret S. Cheung
Graph identification of proteins in tomograms (GRIP-Tomo)
submitted for peer review
null
null
null
q-bio.QM
http://creativecommons.org/licenses/by/4.0/
In this study, we present a method of pattern mining based on network theory that enables the identification of protein structures or complexes from synthetic volume densities, without the knowledge of predefined templates or human biases for refinement. We hypothesized that the topological connectivity of protein structures is invariant, and they are distinctive for the purpose of protein identification from distorted data presented in volume densities. Three-dimensional densities of a protein or a complex from simulated tomographic volumes were transformed into mathematical graphs as observables. We systematically introduced data distortion or defects such as missing fullness of data, the tumbling effect, and the missing wedge effect into the simulated volumes, and varied the distance cutoffs in pixels to capture the varying connectivity between the density cluster centroids in the presence of defects. A similarity score between the graphs from the simulated volumes and the graphs transformed from the physical protein structures in point data was calculated by comparing their network theory order parameters including node degrees, betweenness centrality, and graph densities. By capturing the essential topological features defining the heterogeneous morphologies of a network, we were able to accurately identify proteins and homo-multimeric complexes from ten topologically distinctive samples without realistic noise added. Our approach empowers future developments of tomogram processing by providing pattern mining with interpretability, to enable the classification of single-domain protein native topologies as well as distinct single-domain proteins from multimeric complexes within noisy volumes.
[ { "created": "Sat, 15 Oct 2022 04:51:38 GMT", "version": "v1" } ]
2022-10-18
[ [ "George", "August", "" ], [ "Kim", "Doo Nam", "" ], [ "Moser", "Trevor", "" ], [ "Gildea", "Ian T.", "" ], [ "Evans", "James E.", "" ], [ "Cheung", "Margaret S.", "" ] ]
In this study, we present a method of pattern mining based on network theory that enables the identification of protein structures or complexes from synthetic volume densities, without the knowledge of predefined templates or human biases for refinement. We hypothesized that the topological connectivity of protein structures is invariant, and they are distinctive for the purpose of protein identification from distorted data presented in volume densities. Three-dimensional densities of a protein or a complex from simulated tomographic volumes were transformed into mathematical graphs as observables. We systematically introduced data distortion or defects such as missing fullness of data, the tumbling effect, and the missing wedge effect into the simulated volumes, and varied the distance cutoffs in pixels to capture the varying connectivity between the density cluster centroids in the presence of defects. A similarity score between the graphs from the simulated volumes and the graphs transformed from the physical protein structures in point data was calculated by comparing their network theory order parameters including node degrees, betweenness centrality, and graph densities. By capturing the essential topological features defining the heterogeneous morphologies of a network, we were able to accurately identify proteins and homo-multimeric complexes from ten topologically distinctive samples without realistic noise added. Our approach empowers future developments of tomogram processing by providing pattern mining with interpretability, to enable the classification of single-domain protein native topologies as well as distinct single-domain proteins from multimeric complexes within noisy volumes.
2007.02557
Thomas Caulfield
Mathew Coban, Juliet Morrison PhD, William D. Freeman MD, Evette Radisky PhD, Karine G. Le Roch PhD, Thomas R. Caulfield PhD
Attacking COVID-19 Progression using Multi-Drug Therapy for Synergetic Target Engagement
Main text: 29 pages with references, 1 main table, 6 main figures; Supplemental section: 30 pages, 3 supplemental tables, 4 supplemental figures
Biomolecules 2021, 11(6), 787
10.3390/biom11060787
null
q-bio.BM q-bio.CB
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
COVID-19 is a devastating respiratory and inflammatory illness caused by a new coronavirus that is rapidly spreading throughout the human population. Over the past 6 months, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, has already infected over 11.6 million (25% located in United States) and killed more than 540K people around the world. As we face one of the most challenging times in our recent history, there is an urgent need to identify drug candidates that can attack SARS-CoV-2 on multiple fronts. We have therefore initiated a computational dynamics drug pipeline using molecular modeling, structure simulation, docking and machine learning models to predict the inhibitory activity of several million compounds against two essential SARS-CoV-2 viral proteins and their host protein interactors; S/Ace2, Tmprss2, Cathepsins L and K, and Mpro to prevent binding, membrane fusion and replication of the virus, respectively. All together we generated an ensemble of structural conformations that increase high quality docking outcomes to screen over >6 million compounds including all FDA-approved drugs, drugs under clinical trial (>3000) and an additional >30 million selected chemotypes from fragment libraries. Our results yielded an initial set of 350 high value compounds from both new and FDA-approved compounds that can now be tested experimentally in appropriate biological model systems. We anticipate that our results will initiate screening campaigns and accelerate the discovery of COVID-19 treatments.
[ { "created": "Mon, 6 Jul 2020 07:08:45 GMT", "version": "v1" } ]
2021-06-25
[ [ "Coban", "Mathew", "" ], [ "PhD", "Juliet Morrison", "" ], [ "MD", "William D. Freeman", "" ], [ "PhD", "Evette Radisky", "" ], [ "PhD", "Karine G. Le Roch", "" ], [ "PhD", "Thomas R. Caulfield", "" ] ]
COVID-19 is a devastating respiratory and inflammatory illness caused by a new coronavirus that is rapidly spreading throughout the human population. Over the past 6 months, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, has already infected over 11.6 million (25% located in United States) and killed more than 540K people around the world. As we face one of the most challenging times in our recent history, there is an urgent need to identify drug candidates that can attack SARS-CoV-2 on multiple fronts. We have therefore initiated a computational dynamics drug pipeline using molecular modeling, structure simulation, docking and machine learning models to predict the inhibitory activity of several million compounds against two essential SARS-CoV-2 viral proteins and their host protein interactors; S/Ace2, Tmprss2, Cathepsins L and K, and Mpro to prevent binding, membrane fusion and replication of the virus, respectively. All together we generated an ensemble of structural conformations that increase high quality docking outcomes to screen over >6 million compounds including all FDA-approved drugs, drugs under clinical trial (>3000) and an additional >30 million selected chemotypes from fragment libraries. Our results yielded an initial set of 350 high value compounds from both new and FDA-approved compounds that can now be tested experimentally in appropriate biological model systems. We anticipate that our results will initiate screening campaigns and accelerate the discovery of COVID-19 treatments.
1008.1410
Avner Wallach
Avner Wallach, Danny Eytan, Asaf Gal, Christoph Zrenner, Ron Meir and Shimon Marom
Neuronal Response Clamp
null
null
null
null
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Since the first recordings made of evoked action potentials it has become apparent that the responses of individual neurons to ongoing physiologically relevant input, are highly variable. This variability is manifested in non-stationary behavior of practically every observable neuronal response feature. Here we introduce the Neuronal Response Clamp, a closed-loop technique enabling full control over two important single neuron activity variables: response probability and stimulus-spike latency. The technique is applicable over extended durations (up to several hours), and is effective even on the background of ongoing neuronal network activity. The Response Clamp technique is a powerful tool, extending the voltage-clamp and dynamic-clamp approaches to the neuron's functional level, namely - its spiking behavior.
[ { "created": "Sun, 8 Aug 2010 15:13:12 GMT", "version": "v1" } ]
2010-08-10
[ [ "Wallach", "Avner", "" ], [ "Eytan", "Danny", "" ], [ "Gal", "Asaf", "" ], [ "Zrenner", "Christoph", "" ], [ "Meir", "Ron", "" ], [ "Marom", "Shimon", "" ] ]
Since the first recordings made of evoked action potentials it has become apparent that the responses of individual neurons to ongoing physiologically relevant input, are highly variable. This variability is manifested in non-stationary behavior of practically every observable neuronal response feature. Here we introduce the Neuronal Response Clamp, a closed-loop technique enabling full control over two important single neuron activity variables: response probability and stimulus-spike latency. The technique is applicable over extended durations (up to several hours), and is effective even on the background of ongoing neuronal network activity. The Response Clamp technique is a powerful tool, extending the voltage-clamp and dynamic-clamp approaches to the neuron's functional level, namely - its spiking behavior.
0708.3502
Dietrich Stauffer
D. Stauffer and S. Moss de Oliveira
Child mortality in Penna ageing model
To pages including one figure
null
null
null
q-bio.PE
null
Assuming the deleterious mutations in the Penna ageing model to affect mainly the young ages, we get an enhanced mortality at very young age, followed by a minimum of the mortality, and then the usual exponential increase of mortality with age.
[ { "created": "Sun, 26 Aug 2007 18:27:28 GMT", "version": "v1" } ]
2007-08-28
[ [ "Stauffer", "D.", "" ], [ "de Oliveira", "S. Moss", "" ] ]
Assuming the deleterious mutations in the Penna ageing model to affect mainly the young ages, we get an enhanced mortality at very young age, followed by a minimum of the mortality, and then the usual exponential increase of mortality with age.
2111.09780
Kevin McKee
Kevin L. McKee, Ian C. Crandell, Rishidev Chaudhuri, Randall C. O'Reilly
Locally Learned Synaptic Dropout for Complete Bayesian Inference
30 pages, 8 Figures
null
null
null
q-bio.NC stat.ML
http://creativecommons.org/licenses/by-nc-sa/4.0/
The Bayesian brain hypothesis postulates that the brain accurately operates on statistical distributions according to Bayes' theorem. The random failure of presynaptic vesicles to release neurotransmitters may allow the brain to sample from posterior distributions of network parameters, interpreted as epistemic uncertainty. It has not been shown previously how random failures might allow networks to sample from observed distributions, also known as aleatoric or residual uncertainty. Sampling from both distributions enables probabilistic inference, efficient search, and creative or generative problem solving. We demonstrate that under a population-code based interpretation of neural activity, both types of distribution can be represented and sampled with synaptic failure alone. We first define a biologically constrained neural network and sampling scheme based on synaptic failure and lateral inhibition. Within this framework, we derive drop-out based epistemic uncertainty, then prove an analytic mapping from synaptic efficacy to release probability that allows networks to sample from arbitrary, learned distributions represented by a receiving layer. Second, our result leads to a local learning rule by which synapses adapt their release probabilities. Our result demonstrates complete Bayesian inference, related to the variational learning method of dropout, in a biologically constrained network using only locally-learned synaptic failure rates.
[ { "created": "Thu, 18 Nov 2021 16:23:00 GMT", "version": "v1" }, { "created": "Tue, 23 Nov 2021 16:04:20 GMT", "version": "v2" }, { "created": "Mon, 29 Nov 2021 18:47:26 GMT", "version": "v3" } ]
2021-11-30
[ [ "McKee", "Kevin L.", "" ], [ "Crandell", "Ian C.", "" ], [ "Chaudhuri", "Rishidev", "" ], [ "O'Reilly", "Randall C.", "" ] ]
The Bayesian brain hypothesis postulates that the brain accurately operates on statistical distributions according to Bayes' theorem. The random failure of presynaptic vesicles to release neurotransmitters may allow the brain to sample from posterior distributions of network parameters, interpreted as epistemic uncertainty. It has not been shown previously how random failures might allow networks to sample from observed distributions, also known as aleatoric or residual uncertainty. Sampling from both distributions enables probabilistic inference, efficient search, and creative or generative problem solving. We demonstrate that under a population-code based interpretation of neural activity, both types of distribution can be represented and sampled with synaptic failure alone. We first define a biologically constrained neural network and sampling scheme based on synaptic failure and lateral inhibition. Within this framework, we derive drop-out based epistemic uncertainty, then prove an analytic mapping from synaptic efficacy to release probability that allows networks to sample from arbitrary, learned distributions represented by a receiving layer. Second, our result leads to a local learning rule by which synapses adapt their release probabilities. Our result demonstrates complete Bayesian inference, related to the variational learning method of dropout, in a biologically constrained network using only locally-learned synaptic failure rates.
1210.2908
Oriol G\"uell
Oriol G\"uell, Francesc Sagu\'es, Georg Basler, Zoran Nikoloski, M. \'Angeles Serrano
Assessing the significance of knockout cascades in metabolic networks
null
null
null
null
q-bio.MN
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Complex networks have been shown to be robust against random structural perturbations, but vulnerable against targeted attacks. Robustness analysis usually simulates the removal of individual or sets of nodes, followed by the assessment of the inflicted damage. For complex metabolic networks, it has been suggested that evolutionary pressure may favor robustness against reaction removal. However, the removal of a reaction and its impact on the network may as well be interpreted as selective regulation of pathway activities, suggesting a tradeoff between the efficiency of regulation and vulnerability. Here, we employ a cascading failure algorithm to simulate the removal of single and pairs of reactions from the metabolic networks of two organisms, and estimate the significance of the results using two different null models: degree preserving and mass-balanced randomization. Our analysis suggests that evolutionary pressure promotes larger cascades of non-viable reactions, and thus favors the ability of efficient metabolic regulation at the expense of robustness.
[ { "created": "Wed, 10 Oct 2012 13:28:01 GMT", "version": "v1" } ]
2012-11-13
[ [ "Güell", "Oriol", "" ], [ "Sagués", "Francesc", "" ], [ "Basler", "Georg", "" ], [ "Nikoloski", "Zoran", "" ], [ "Serrano", "M. Ángeles", "" ] ]
Complex networks have been shown to be robust against random structural perturbations, but vulnerable against targeted attacks. Robustness analysis usually simulates the removal of individual or sets of nodes, followed by the assessment of the inflicted damage. For complex metabolic networks, it has been suggested that evolutionary pressure may favor robustness against reaction removal. However, the removal of a reaction and its impact on the network may as well be interpreted as selective regulation of pathway activities, suggesting a tradeoff between the efficiency of regulation and vulnerability. Here, we employ a cascading failure algorithm to simulate the removal of single and pairs of reactions from the metabolic networks of two organisms, and estimate the significance of the results using two different null models: degree preserving and mass-balanced randomization. Our analysis suggests that evolutionary pressure promotes larger cascades of non-viable reactions, and thus favors the ability of efficient metabolic regulation at the expense of robustness.
q-bio/0601028
Ila Fiete
Ila R. Fiete and H. Sebastian Seung
Gradient learning in spiking neural networks by dynamic perturbation of conductances
5 pages; 1 figure; submitted to PRL
Phys. Rev. Lett. 97, 048104 (2006)
10.1103/PhysRevLett.97.048104
null
q-bio.NC
null
We present a method of estimating the gradient of an objective function with respect to the synaptic weights of a spiking neural network. The method works by measuring the fluctuations in the objective function in response to dynamic perturbation of the membrane conductances of the neurons. It is compatible with recurrent networks of conductance-based model neurons with dynamic synapses. The method can be interpreted as a biologically plausible synaptic learning rule, if the dynamic perturbations are generated by a special class of ``empiric'' synapses driven by random spike trains from an external source.
[ { "created": "Thu, 19 Jan 2006 23:19:55 GMT", "version": "v1" } ]
2007-05-23
[ [ "Fiete", "Ila R.", "" ], [ "Seung", "H. Sebastian", "" ] ]
We present a method of estimating the gradient of an objective function with respect to the synaptic weights of a spiking neural network. The method works by measuring the fluctuations in the objective function in response to dynamic perturbation of the membrane conductances of the neurons. It is compatible with recurrent networks of conductance-based model neurons with dynamic synapses. The method can be interpreted as a biologically plausible synaptic learning rule, if the dynamic perturbations are generated by a special class of ``empiric'' synapses driven by random spike trains from an external source.
2106.14732
Alan D. Rendall
Burcu G\"urb\"uz and Alan D. Rendall
Analysis of a model of the Calvin cycle with diffusion of ATP
null
null
null
null
q-bio.MN
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The dynamics of a mathematical model of the Calvin cycle, which is part of photosynthesis, is analysed. Since diffusion of ATP is included in the model a system of reaction-diffusion equations is obtained. It is proved that for a suitable choice of parameters there exist spatially inhomogeneous positive steady states, in fact infinitely many of them. It is also shown that all positive steady states, homogeneous and inhomogeneous, are nonlinearly unstable. The only smooth steady state which could be stable is a trivial one, where all concentrations except that of ATP are zero. It is found that in the spatially homogeneous case there are steady states with the property that the linearization about that state has eigenvalues which are not real, indicating the presence of oscillations. Numerical simulations exhibit solutions for which the concentrations are not monotone functions of time.
[ { "created": "Mon, 28 Jun 2021 14:03:09 GMT", "version": "v1" } ]
2021-06-29
[ [ "Gürbüz", "Burcu", "" ], [ "Rendall", "Alan D.", "" ] ]
The dynamics of a mathematical model of the Calvin cycle, which is part of photosynthesis, is analysed. Since diffusion of ATP is included in the model a system of reaction-diffusion equations is obtained. It is proved that for a suitable choice of parameters there exist spatially inhomogeneous positive steady states, in fact infinitely many of them. It is also shown that all positive steady states, homogeneous and inhomogeneous, are nonlinearly unstable. The only smooth steady state which could be stable is a trivial one, where all concentrations except that of ATP are zero. It is found that in the spatially homogeneous case there are steady states with the property that the linearization about that state has eigenvalues which are not real, indicating the presence of oscillations. Numerical simulations exhibit solutions for which the concentrations are not monotone functions of time.
2107.03387
Tim Cvetko
Tim Cvetko, Tinkara Robek
Sleep syndromes onset detection based on automatic sleep staging algorithm
12 pages, 3 figures
null
null
null
q-bio.NC cs.LG eess.SP
http://creativecommons.org/licenses/by/4.0/
In this paper, we propose a novel method and a practical approach to predicting early onsets of sleep syndromes, including restless leg syndrome, insomnia, based on an algorithm that is comprised of two modules. A Fast Fourier Transform is applied to 30 seconds long epochs of EEG recordings to provide localized time-frequency information, and a deep convolutional LSTM neural network is trained for sleep stage classification. Automating sleep stages detection from EEG data offers great potential to tackling sleep irregularities on a daily basis. Thereby, a novel approach for sleep stage classification is proposed which combines the best of signal processing and statistics. In this study, we used the PhysioNet Sleep European Data Format (EDF) Database. The code evaluation showed impressive results, reaching an accuracy of 86.43, precision of 77.76, recall of 93,32, F1-score of 89.12 with the final mean false error loss of 0.09.
[ { "created": "Wed, 7 Jul 2021 15:38:47 GMT", "version": "v1" } ]
2021-07-09
[ [ "Cvetko", "Tim", "" ], [ "Robek", "Tinkara", "" ] ]
In this paper, we propose a novel method and a practical approach to predicting early onsets of sleep syndromes, including restless leg syndrome, insomnia, based on an algorithm that is comprised of two modules. A Fast Fourier Transform is applied to 30 seconds long epochs of EEG recordings to provide localized time-frequency information, and a deep convolutional LSTM neural network is trained for sleep stage classification. Automating sleep stages detection from EEG data offers great potential to tackling sleep irregularities on a daily basis. Thereby, a novel approach for sleep stage classification is proposed which combines the best of signal processing and statistics. In this study, we used the PhysioNet Sleep European Data Format (EDF) Database. The code evaluation showed impressive results, reaching an accuracy of 86.43, precision of 77.76, recall of 93,32, F1-score of 89.12 with the final mean false error loss of 0.09.
1108.6062
Konstantin Klemm
Gunnar Boldhaus, Florian Greil, Konstantin Klemm
Prediction of lethal and synthetically lethal knock-outs in regulatory networks
published version, 10 pages, 6 figures, 2 tables; supplement at http://www.bioinf.uni-leipzig.de/publications/supplements/11-018
Theory in Biosciences 132, 17-25 (2013)
10.1007/s12064-012-0164-1
null
q-bio.MN
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The complex interactions involved in regulation of a cell's function are captured by its interaction graph. More often than not, detailed knowledge about enhancing or suppressive regulatory influences and cooperative effects is lacking and merely the presence or absence of directed interactions is known. Here we investigate to which extent such reduced information allows to forecast the effect of a knock-out or a combination of knock-outs. Specifically we ask in how far the lethality of eliminating nodes may be predicted by their network centrality, such as degree and betweenness, without knowing the function of the system. The function is taken as the ability to reproduce a fixed point under a discrete Boolean dynamics. We investigate two types of stochastically generated networks: fully random networks and structures grown with a mechanism of node duplication and subsequent divergence of interactions. On all networks we find that the out-degree is a good predictor of the lethality of a single node knock-out. For knock-outs of node pairs, the fraction of successors shared between the two knocked-out nodes (out-overlap) is a good predictor of synthetic lethality. Out-degree and out-overlap are locally defined and computationally simple centrality measures that provide a predictive power close to the optimal predictor.
[ { "created": "Tue, 30 Aug 2011 20:00:58 GMT", "version": "v1" }, { "created": "Thu, 14 Feb 2013 14:45:41 GMT", "version": "v2" } ]
2013-02-15
[ [ "Boldhaus", "Gunnar", "" ], [ "Greil", "Florian", "" ], [ "Klemm", "Konstantin", "" ] ]
The complex interactions involved in regulation of a cell's function are captured by its interaction graph. More often than not, detailed knowledge about enhancing or suppressive regulatory influences and cooperative effects is lacking and merely the presence or absence of directed interactions is known. Here we investigate to which extent such reduced information allows to forecast the effect of a knock-out or a combination of knock-outs. Specifically we ask in how far the lethality of eliminating nodes may be predicted by their network centrality, such as degree and betweenness, without knowing the function of the system. The function is taken as the ability to reproduce a fixed point under a discrete Boolean dynamics. We investigate two types of stochastically generated networks: fully random networks and structures grown with a mechanism of node duplication and subsequent divergence of interactions. On all networks we find that the out-degree is a good predictor of the lethality of a single node knock-out. For knock-outs of node pairs, the fraction of successors shared between the two knocked-out nodes (out-overlap) is a good predictor of synthetic lethality. Out-degree and out-overlap are locally defined and computationally simple centrality measures that provide a predictive power close to the optimal predictor.
1904.07113
Anindita Bhadra
Debottam Bhattacharjee, Rohan Sarkar, Shubhra Sau and Anindita Bhadra
A tale of two species: How humans shape dog behaviour in urban habitats
3 figures, 14 pages of supplementary material
null
null
null
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Species inhabiting urban environments experience enormous anthropogenic stress. Behavioural plasticity and flexibility of temperament are crucial to successful urban-adaptation. Urban free-ranging dogs experience variable human impact, from positive to negative and represent an ideal system to evaluate the effects of human-induced stress on behavioural plasticity. We tested 600 adult dogs from 60 sites across India, categorised as high - HF, low - LF, and intermediate - IF human flux zones, to understand their sociability towards an unfamiliar human. Dogs in the HF and IF zones were bolder and as compared to their shy counterparts in LF zones. The IF zone dogs were the most sociable. This is the first-ever study aimed to understand how the experiences of interactions with humans in its immediate environment might shape the responses of an animal to humans. This is very relevant in the context of human-animal conflict induced by rapid urbanization and habitat loss across the world.
[ { "created": "Fri, 12 Apr 2019 10:59:47 GMT", "version": "v1" } ]
2019-04-16
[ [ "Bhattacharjee", "Debottam", "" ], [ "Sarkar", "Rohan", "" ], [ "Sau", "Shubhra", "" ], [ "Bhadra", "Anindita", "" ] ]
Species inhabiting urban environments experience enormous anthropogenic stress. Behavioural plasticity and flexibility of temperament are crucial to successful urban-adaptation. Urban free-ranging dogs experience variable human impact, from positive to negative and represent an ideal system to evaluate the effects of human-induced stress on behavioural plasticity. We tested 600 adult dogs from 60 sites across India, categorised as high - HF, low - LF, and intermediate - IF human flux zones, to understand their sociability towards an unfamiliar human. Dogs in the HF and IF zones were bolder and as compared to their shy counterparts in LF zones. The IF zone dogs were the most sociable. This is the first-ever study aimed to understand how the experiences of interactions with humans in its immediate environment might shape the responses of an animal to humans. This is very relevant in the context of human-animal conflict induced by rapid urbanization and habitat loss across the world.
2209.04406
Camille Noufi
Camille Noufi, Adam C. Lammert, Daryush D. Mehta, James R. Williamson, Gregory Ciccarelli, Douglas Sturim, Jordan R. Green, Thomas F. Quatieri and Thomas F. Campbell
Longitudinal Acoustic Speech Tracking Following Pediatric Traumatic Brain Injury
null
null
null
null
q-bio.NC cs.SD eess.AS
http://creativecommons.org/licenses/by-nc-sa/4.0/
Recommendations for common outcome measures following pediatric traumatic brain injury (TBI) support the integration of instrumental measurements alongside perceptual assessment in recovery and treatment plans. A comprehensive set of sensitive, robust and non-invasive measurements is therefore essential in assessing variations in speech characteristics over time following pediatric TBI. In this article, we study the changes in the acoustic speech patterns of a pediatric cohort of ten subjects diagnosed with severe TBI. We extract a diverse set of both well-known and novel acoustic features from child speech recorded throughout the year after the child produced intelligible words. These features are analyzed individually and by speech subsystem, within-subject and across the cohort. As a group, older children exhibit highly significant (p<0.01) increases in pitch variation and phoneme diversity, shortened pause length, and steadying articulation rate variability. Younger children exhibit similar steadied rate variability alongside an increase in formant-based articulation complexity. Correlation analysis of the feature set with age and comparisons to normative developmental data confirm that age at injury plays a significant role in framing the recovery trajectory. Nearly all speech features significantly change (p<0.05) for the cohort as a whole, confirming that acoustic measures supplementing perceptual assessment are needed to identify efficacious treatment targets for speech therapy following TBI.
[ { "created": "Fri, 9 Sep 2022 17:18:41 GMT", "version": "v1" } ]
2022-09-12
[ [ "Noufi", "Camille", "" ], [ "Lammert", "Adam C.", "" ], [ "Mehta", "Daryush D.", "" ], [ "Williamson", "James R.", "" ], [ "Ciccarelli", "Gregory", "" ], [ "Sturim", "Douglas", "" ], [ "Green", "Jordan R.", "" ], [ "Quatieri", "Thomas F.", "" ], [ "Campbell", "Thomas F.", "" ] ]
Recommendations for common outcome measures following pediatric traumatic brain injury (TBI) support the integration of instrumental measurements alongside perceptual assessment in recovery and treatment plans. A comprehensive set of sensitive, robust and non-invasive measurements is therefore essential in assessing variations in speech characteristics over time following pediatric TBI. In this article, we study the changes in the acoustic speech patterns of a pediatric cohort of ten subjects diagnosed with severe TBI. We extract a diverse set of both well-known and novel acoustic features from child speech recorded throughout the year after the child produced intelligible words. These features are analyzed individually and by speech subsystem, within-subject and across the cohort. As a group, older children exhibit highly significant (p<0.01) increases in pitch variation and phoneme diversity, shortened pause length, and steadying articulation rate variability. Younger children exhibit similar steadied rate variability alongside an increase in formant-based articulation complexity. Correlation analysis of the feature set with age and comparisons to normative developmental data confirm that age at injury plays a significant role in framing the recovery trajectory. Nearly all speech features significantly change (p<0.05) for the cohort as a whole, confirming that acoustic measures supplementing perceptual assessment are needed to identify efficacious treatment targets for speech therapy following TBI.
1808.04075
Dirk Ostwald
Dirk Ostwald, Sebastian Schneider, Rasmus Bruckner, Lilla Horvath
Random field theory-based p-values: A review of the SPM implementation
null
null
null
null
q-bio.QM
http://creativecommons.org/licenses/by-sa/4.0/
P-values and null-hypothesis significance testing are popular data-analytical tools in functional neuroimaging. Sparked by the analysis of resting-state fMRI data, there has been a resurgence of interest in the validity of some of the p-values evaluated with the widely used software SPM in recent years. The default parametric p-values reported in SPM are based on the application of results from random field theory to statistical parametric maps, a framework commonly referred to as RFT. While RFT was established two decades ago and has since been applied in a plethora of fMRI studies, there does not exist a unified documentation of the mathematical and computational underpinnings of RFT as implemented in current versions of SPM. Here, we provide such a documentation with the aim of contributing to contemporary efforts towards higher levels of computational transparency in functional neuroimaging.
[ { "created": "Mon, 13 Aug 2018 06:18:50 GMT", "version": "v1" }, { "created": "Sat, 19 Jan 2019 12:57:02 GMT", "version": "v2" }, { "created": "Mon, 9 Aug 2021 12:17:36 GMT", "version": "v3" } ]
2021-08-10
[ [ "Ostwald", "Dirk", "" ], [ "Schneider", "Sebastian", "" ], [ "Bruckner", "Rasmus", "" ], [ "Horvath", "Lilla", "" ] ]
P-values and null-hypothesis significance testing are popular data-analytical tools in functional neuroimaging. Sparked by the analysis of resting-state fMRI data, there has been a resurgence of interest in the validity of some of the p-values evaluated with the widely used software SPM in recent years. The default parametric p-values reported in SPM are based on the application of results from random field theory to statistical parametric maps, a framework commonly referred to as RFT. While RFT was established two decades ago and has since been applied in a plethora of fMRI studies, there does not exist a unified documentation of the mathematical and computational underpinnings of RFT as implemented in current versions of SPM. Here, we provide such a documentation with the aim of contributing to contemporary efforts towards higher levels of computational transparency in functional neuroimaging.
2205.03135
Simon Olsson
Christopher Kolloff and Simon Olsson
Machine Learning in Molecular Dynamics Simulations of Biomolecular Systems
36 pages, 4 figures
null
null
null
q-bio.BM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Machine learning (ML) has emerged as a pervasive tool in science, engineering, and beyond. Its success has also led to several synergies with molecular dynamics (MD) simulations, which we use to identify and characterize the major metastable states of molecular systems. Typically, we aim to determine the relative stabilities of these states and how rapidly they interchange. This information allows mechanistic descriptions of molecular mechanisms, enables a quantitative comparison with experiments, and facilitates their rational design. ML impacts all aspects of MD simulations -- from analyzing the data and accelerating sampling to defining more efficient or more accurate simulation models.
[ { "created": "Fri, 6 May 2022 10:56:51 GMT", "version": "v1" } ]
2022-05-09
[ [ "Kolloff", "Christopher", "" ], [ "Olsson", "Simon", "" ] ]
Machine learning (ML) has emerged as a pervasive tool in science, engineering, and beyond. Its success has also led to several synergies with molecular dynamics (MD) simulations, which we use to identify and characterize the major metastable states of molecular systems. Typically, we aim to determine the relative stabilities of these states and how rapidly they interchange. This information allows mechanistic descriptions of molecular mechanisms, enables a quantitative comparison with experiments, and facilitates their rational design. ML impacts all aspects of MD simulations -- from analyzing the data and accelerating sampling to defining more efficient or more accurate simulation models.
1812.11384
William Bialek
Victoria Antonetti, William Bialek, Thomas Gregor, Gentian Muhaxheri, Mariela Petkova, and Martin Scheeler
Precise spatial scaling in the early fly embryo
null
null
null
null
q-bio.MN physics.bio-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The early fly embryo offers a relatively pure version of the problem of spatial scaling in biological pattern formation. Within three hours, a "blueprint" for the final segmented body plan of the animal is visible in striped patterns of gene expression. We measure the positions of these stripes in an ensemble of 100+ embryos from a laboratory strain of Drosophila melanogaster, under controlled conditions. These embryos vary in length by only 4% (rms), yet stripes are positioned with 1% accuracy; precision and scaling of the pattern are intertwined. We can see directly the variation of absolute stripe positions with length, and the precision is so high as to exclude alternatives, such as combinations of unscaled signals from the two ends of the embryo.
[ { "created": "Sat, 29 Dec 2018 15:38:52 GMT", "version": "v1" } ]
2019-01-01
[ [ "Antonetti", "Victoria", "" ], [ "Bialek", "William", "" ], [ "Gregor", "Thomas", "" ], [ "Muhaxheri", "Gentian", "" ], [ "Petkova", "Mariela", "" ], [ "Scheeler", "Martin", "" ] ]
The early fly embryo offers a relatively pure version of the problem of spatial scaling in biological pattern formation. Within three hours, a "blueprint" for the final segmented body plan of the animal is visible in striped patterns of gene expression. We measure the positions of these stripes in an ensemble of 100+ embryos from a laboratory strain of Drosophila melanogaster, under controlled conditions. These embryos vary in length by only 4% (rms), yet stripes are positioned with 1% accuracy; precision and scaling of the pattern are intertwined. We can see directly the variation of absolute stripe positions with length, and the precision is so high as to exclude alternatives, such as combinations of unscaled signals from the two ends of the embryo.
1707.03532
Brian Camley
Brian A. Camley and Wouter-Jan Rappel
Cell-to-cell variation sets a tissue-rheology-dependent bound on collective gradient sensing
null
PNAS (2017)
10.1073/pnas.1712309114
null
q-bio.CB cond-mat.soft physics.bio-ph q-bio.TO
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
When a single cell senses a chemical gradient and chemotaxes, stochastic receptor-ligand binding can be a fundamental limit to the cell's accuracy. For clusters of cells responding to gradients, however, there is a critical difference: even genetically identical cells have differing responses to chemical signals. With theory and simulation, we show collective chemotaxis is limited by cell-to-cell variation in signaling. We find that when different cells cooperate the resulting bias can be much larger than the effects of ligand-receptor binding. Specifically, when a strongly-responding cell is at one end of a cell cluster, cluster motion is biased toward that cell. These errors are mitigated if clusters average measurements over times long enough for cells to rearrange. In consequence, fluid clusters are better able to sense gradients: we derive a link between cluster accuracy, cell-to-cell variation, and the cluster rheology. Because of this connection, increasing the noisiness of individual cell motion can actually increase the collective accuracy of a cluster by improving fluidity.
[ { "created": "Wed, 12 Jul 2017 04:01:44 GMT", "version": "v1" } ]
2017-11-09
[ [ "Camley", "Brian A.", "" ], [ "Rappel", "Wouter-Jan", "" ] ]
When a single cell senses a chemical gradient and chemotaxes, stochastic receptor-ligand binding can be a fundamental limit to the cell's accuracy. For clusters of cells responding to gradients, however, there is a critical difference: even genetically identical cells have differing responses to chemical signals. With theory and simulation, we show collective chemotaxis is limited by cell-to-cell variation in signaling. We find that when different cells cooperate the resulting bias can be much larger than the effects of ligand-receptor binding. Specifically, when a strongly-responding cell is at one end of a cell cluster, cluster motion is biased toward that cell. These errors are mitigated if clusters average measurements over times long enough for cells to rearrange. In consequence, fluid clusters are better able to sense gradients: we derive a link between cluster accuracy, cell-to-cell variation, and the cluster rheology. Because of this connection, increasing the noisiness of individual cell motion can actually increase the collective accuracy of a cluster by improving fluidity.
0805.3583
Vladimir Ivancevic
Vladimir G. Ivancevic
New Mechanics of Traumatic Brain Injury
18 pages, 1 figure, Latex
null
null
null
q-bio.TO
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The prediction and prevention of traumatic brain injury is a very important aspect of preventive medical science. This paper proposes a new coupled loading-rate hypothesis for the traumatic brain injury (TBI), which states that the main cause of the TBI is an external Euclidean jolt, or SE(3)-jolt, an impulsive loading that strikes the head in several coupled degrees-of-freedom simultaneously. To show this, based on the previously defined covariant force law, we formulate the coupled Newton-Euler dynamics of brain's micro-motions within the cerebrospinal fluid and derive from it the coupled SE(3)-jolt dynamics. The SE(3)-jolt is a cause of the TBI in two forms of brain's rapid discontinuous deformations: translational dislocations and rotational disclinations. Brain's dislocations and disclinations, caused by the SE(3)-jolt, are described using the Cosserat multipolar viscoelastic continuum brain model. Keywords: Traumatic brain injuries, coupled loading-rate hypothesis, Euclidean jolt, coupled Newton-Euler dynamics, brain's dislocations and disclinations
[ { "created": "Fri, 23 May 2008 06:14:02 GMT", "version": "v1" }, { "created": "Wed, 3 Sep 2008 04:18:08 GMT", "version": "v2" }, { "created": "Tue, 18 Nov 2008 02:16:26 GMT", "version": "v3" } ]
2008-11-18
[ [ "Ivancevic", "Vladimir G.", "" ] ]
The prediction and prevention of traumatic brain injury is a very important aspect of preventive medical science. This paper proposes a new coupled loading-rate hypothesis for the traumatic brain injury (TBI), which states that the main cause of the TBI is an external Euclidean jolt, or SE(3)-jolt, an impulsive loading that strikes the head in several coupled degrees-of-freedom simultaneously. To show this, based on the previously defined covariant force law, we formulate the coupled Newton-Euler dynamics of brain's micro-motions within the cerebrospinal fluid and derive from it the coupled SE(3)-jolt dynamics. The SE(3)-jolt is a cause of the TBI in two forms of brain's rapid discontinuous deformations: translational dislocations and rotational disclinations. Brain's dislocations and disclinations, caused by the SE(3)-jolt, are described using the Cosserat multipolar viscoelastic continuum brain model. Keywords: Traumatic brain injuries, coupled loading-rate hypothesis, Euclidean jolt, coupled Newton-Euler dynamics, brain's dislocations and disclinations
2111.04107
Pavol Drot\'ar
Pavol Drot\'ar, Arian Rokkum Jamasb, Ben Day, C\u{a}t\u{a}lina Cangea, Pietro Li\`o
Structure-aware generation of drug-like molecules
null
null
null
null
q-bio.QM cs.LG
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Structure-based drug design involves finding ligand molecules that exhibit structural and chemical complementarity to protein pockets. Deep generative methods have shown promise in proposing novel molecules from scratch (de-novo design), avoiding exhaustive virtual screening of chemical space. Most generative de-novo models fail to incorporate detailed ligand-protein interactions and 3D pocket structures. We propose a novel supervised model that generates molecular graphs jointly with 3D pose in a discretised molecular space. Molecules are built atom-by-atom inside pockets, guided by structural information from crystallographic data. We evaluate our model using a docking benchmark and find that guided generation improves predicted binding affinities by 8% and drug-likeness scores by 10% over the baseline. Furthermore, our model proposes molecules with binding scores exceeding some known ligands, which could be useful in future wet-lab studies.
[ { "created": "Sun, 7 Nov 2021 15:19:54 GMT", "version": "v1" } ]
2021-11-09
[ [ "Drotár", "Pavol", "" ], [ "Jamasb", "Arian Rokkum", "" ], [ "Day", "Ben", "" ], [ "Cangea", "Cătălina", "" ], [ "Liò", "Pietro", "" ] ]
Structure-based drug design involves finding ligand molecules that exhibit structural and chemical complementarity to protein pockets. Deep generative methods have shown promise in proposing novel molecules from scratch (de-novo design), avoiding exhaustive virtual screening of chemical space. Most generative de-novo models fail to incorporate detailed ligand-protein interactions and 3D pocket structures. We propose a novel supervised model that generates molecular graphs jointly with 3D pose in a discretised molecular space. Molecules are built atom-by-atom inside pockets, guided by structural information from crystallographic data. We evaluate our model using a docking benchmark and find that guided generation improves predicted binding affinities by 8% and drug-likeness scores by 10% over the baseline. Furthermore, our model proposes molecules with binding scores exceeding some known ligands, which could be useful in future wet-lab studies.
2002.08813
Alain Destexhe
Alain Destexhe and Jonathan D. Touboul
Is there sufficient evidence for criticality in cortical systems?
null
null
null
null
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Many studies have found evidence that the brain operates at a critical point, a processus known as self-organized criticality. A recent paper found remarkable scalings suggestive of criticality in systems as different as neural cultures, anesthetized or awake brains. We point out here that the diversity of these states would question any claimed role of criticality in information processing. Furthermore, we show that two non-critical systems pass all the tests for criticality, a control that was not provided in the original article. We conclude that such false positives demonstrate that the presence of criticality in the brain is still not proven and that we need better methods that scaling analyses.
[ { "created": "Thu, 20 Feb 2020 15:47:41 GMT", "version": "v1" }, { "created": "Fri, 10 Jul 2020 19:26:44 GMT", "version": "v2" }, { "created": "Mon, 28 Dec 2020 16:05:58 GMT", "version": "v3" } ]
2020-12-29
[ [ "Destexhe", "Alain", "" ], [ "Touboul", "Jonathan D.", "" ] ]
Many studies have found evidence that the brain operates at a critical point, a processus known as self-organized criticality. A recent paper found remarkable scalings suggestive of criticality in systems as different as neural cultures, anesthetized or awake brains. We point out here that the diversity of these states would question any claimed role of criticality in information processing. Furthermore, we show that two non-critical systems pass all the tests for criticality, a control that was not provided in the original article. We conclude that such false positives demonstrate that the presence of criticality in the brain is still not proven and that we need better methods that scaling analyses.
2405.19221
Megan Peters
Seyedmehdi Orouji, Martin C. Liu, Tal Korem, Megan A. K. Peters
Domain adaptation in small-scale and heterogeneous biological datasets
main manuscript + supplement
null
null
null
q-bio.QM cs.LG
http://creativecommons.org/licenses/by/4.0/
Machine learning techniques are steadily becoming more important in modern biology, and are used to build predictive models, discover patterns, and investigate biological problems. However, models trained on one dataset are often not generalizable to other datasets from different cohorts or laboratories, due to differences in the statistical properties of these datasets. These could stem from technical differences, such as the measurement technique used, or from relevant biological differences between the populations studied. Domain adaptation, a type of transfer learning, can alleviate this problem by aligning the statistical distributions of features and samples among different datasets so that similar models can be applied across them. However, a majority of state-of-the-art domain adaptation methods are designed to work with large-scale data, mostly text and images, while biological datasets often suffer from small sample sizes, and possess complexities such as heterogeneity of the feature space. This Review aims to synthetically discuss domain adaptation methods in the context of small-scale and highly heterogeneous biological data. We describe the benefits and challenges of domain adaptation in biological research and critically discuss some of its objectives, strengths, and weaknesses through key representative methodologies. We argue for the incorporation of domain adaptation techniques to the computational biologist's toolkit, with further development of customized approaches.
[ { "created": "Wed, 29 May 2024 16:01:15 GMT", "version": "v1" } ]
2024-05-30
[ [ "Orouji", "Seyedmehdi", "" ], [ "Liu", "Martin C.", "" ], [ "Korem", "Tal", "" ], [ "Peters", "Megan A. K.", "" ] ]
Machine learning techniques are steadily becoming more important in modern biology, and are used to build predictive models, discover patterns, and investigate biological problems. However, models trained on one dataset are often not generalizable to other datasets from different cohorts or laboratories, due to differences in the statistical properties of these datasets. These could stem from technical differences, such as the measurement technique used, or from relevant biological differences between the populations studied. Domain adaptation, a type of transfer learning, can alleviate this problem by aligning the statistical distributions of features and samples among different datasets so that similar models can be applied across them. However, a majority of state-of-the-art domain adaptation methods are designed to work with large-scale data, mostly text and images, while biological datasets often suffer from small sample sizes, and possess complexities such as heterogeneity of the feature space. This Review aims to synthetically discuss domain adaptation methods in the context of small-scale and highly heterogeneous biological data. We describe the benefits and challenges of domain adaptation in biological research and critically discuss some of its objectives, strengths, and weaknesses through key representative methodologies. We argue for the incorporation of domain adaptation techniques to the computational biologist's toolkit, with further development of customized approaches.
2405.06836
Salma Ahmed
Salma J. Ahmed, Mustafa A. Elattar
Improving Targeted Molecule Generation through Language Model Fine-Tuning Via Reinforcement Learning
null
null
null
null
q-bio.BM cs.LG
http://creativecommons.org/licenses/by-nc-nd/4.0/
Developing new drugs is laborious and costly, demanding extensive time investment. In this study, we introduce an innovative de-novo drug design strategy, which harnesses the capabilities of language models to devise targeted drugs for specific proteins. Employing a Reinforcement Learning (RL) framework utilizing Proximal Policy Optimization (PPO), we refine the model to acquire a policy for generating drugs tailored to protein targets. Our method integrates a composite reward function, combining considerations of drug-target interaction and molecular validity. Following RL fine-tuning, our approach demonstrates promising outcomes, yielding notable improvements in molecular validity, interaction efficacy, and critical chemical properties, achieving 65.37 for Quantitative Estimation of Drug-likeness (QED), 321.55 for Molecular Weight (MW), and 4.47 for Octanol-Water Partition Coefficient (logP), respectively. Furthermore, out of the generated drugs, only 0.041\% do not exhibit novelty.
[ { "created": "Fri, 10 May 2024 22:19:12 GMT", "version": "v1" } ]
2024-05-14
[ [ "Ahmed", "Salma J.", "" ], [ "Elattar", "Mustafa A.", "" ] ]
Developing new drugs is laborious and costly, demanding extensive time investment. In this study, we introduce an innovative de-novo drug design strategy, which harnesses the capabilities of language models to devise targeted drugs for specific proteins. Employing a Reinforcement Learning (RL) framework utilizing Proximal Policy Optimization (PPO), we refine the model to acquire a policy for generating drugs tailored to protein targets. Our method integrates a composite reward function, combining considerations of drug-target interaction and molecular validity. Following RL fine-tuning, our approach demonstrates promising outcomes, yielding notable improvements in molecular validity, interaction efficacy, and critical chemical properties, achieving 65.37 for Quantitative Estimation of Drug-likeness (QED), 321.55 for Molecular Weight (MW), and 4.47 for Octanol-Water Partition Coefficient (logP), respectively. Furthermore, out of the generated drugs, only 0.041\% do not exhibit novelty.
2303.00864
Tom Chou
Mingtao Xia, Xiangting Li, Tom Chou
Overcompensation of transient and permanent death rate increases in age-structured models with cannibalistic interactions
19 pages including mathematical appendices, 4 figures
null
null
null
q-bio.PE q-bio.QM
http://creativecommons.org/licenses/by-nc-nd/4.0/
There has been renewed interest in understanding the mathematical structure of ecological population models that lead to overcompensation, the process by which a population recovers to a higher level after suffering a permanent increase in predation or harvesting. Here, we apply a recently formulated kinetic population theory to formally construct an age-structured single-species population model that includes a cannibalistic interaction in which older individuals prey on younger ones. Depending on the age-dependent structure of this interaction, our model can exhibit transient or steady-state overcompensation of an increased death rate as well as oscillations of the total population, both phenomena that have been observed in ecological systems. Analytic and numerical analysis of our model reveals sufficient conditions for overcompensation and oscillations. We also show how our structured population partial integrodifferential equation (PIDE) model can be reduced to coupled ODE models representing piecewise constant parameter domains, providing additional mathematical insight into the emergence of overcompensation.
[ { "created": "Wed, 1 Mar 2023 23:31:17 GMT", "version": "v1" }, { "created": "Fri, 15 Mar 2024 03:27:21 GMT", "version": "v2" } ]
2024-03-18
[ [ "Xia", "Mingtao", "" ], [ "Li", "Xiangting", "" ], [ "Chou", "Tom", "" ] ]
There has been renewed interest in understanding the mathematical structure of ecological population models that lead to overcompensation, the process by which a population recovers to a higher level after suffering a permanent increase in predation or harvesting. Here, we apply a recently formulated kinetic population theory to formally construct an age-structured single-species population model that includes a cannibalistic interaction in which older individuals prey on younger ones. Depending on the age-dependent structure of this interaction, our model can exhibit transient or steady-state overcompensation of an increased death rate as well as oscillations of the total population, both phenomena that have been observed in ecological systems. Analytic and numerical analysis of our model reveals sufficient conditions for overcompensation and oscillations. We also show how our structured population partial integrodifferential equation (PIDE) model can be reduced to coupled ODE models representing piecewise constant parameter domains, providing additional mathematical insight into the emergence of overcompensation.
q-bio/0701025
Agnes Szejka
Agnes Szejka, Barbara Drossel
Evolution of Canalizing Boolean Networks
8 pages, 10 figures; revised and extended version
Eur. Phys. J. B 56, 373-380 (2007)
10.1140/epjb/e2007-00135-2
null
q-bio.PE q-bio.MN
null
Boolean networks with canalizing functions are used to model gene regulatory networks. In order to learn how such networks may behave under evolutionary forces, we simulate the evolution of a single Boolean network by means of an adaptive walk, which allows us to explore the fitness landscape. Mutations change the connections and the functions of the nodes. Our fitness criterion is the robustness of the dynamical attractors against small perturbations. We find that with this fitness criterion the global maximum is always reached and that there is a huge neutral space of 100% fitness. Furthermore, in spite of having such a high degree of robustness, the evolved networks still share many features with "chaotic" networks.
[ { "created": "Wed, 17 Jan 2007 18:27:26 GMT", "version": "v1" }, { "created": "Fri, 29 Jun 2007 08:54:02 GMT", "version": "v2" } ]
2011-11-09
[ [ "Szejka", "Agnes", "" ], [ "Drossel", "Barbara", "" ] ]
Boolean networks with canalizing functions are used to model gene regulatory networks. In order to learn how such networks may behave under evolutionary forces, we simulate the evolution of a single Boolean network by means of an adaptive walk, which allows us to explore the fitness landscape. Mutations change the connections and the functions of the nodes. Our fitness criterion is the robustness of the dynamical attractors against small perturbations. We find that with this fitness criterion the global maximum is always reached and that there is a huge neutral space of 100% fitness. Furthermore, in spite of having such a high degree of robustness, the evolved networks still share many features with "chaotic" networks.
1903.01652
Margaret Frank
Mao Li, Margaret H. Frank, and Zo\"e Migicovsky
ColourQuant: a high-throughput technique to extract and quantify colour phenotypes from plant images
null
null
null
null
q-bio.QM
http://creativecommons.org/licenses/by-sa/4.0/
Colour patterning contributes to important plant traits that influence ecological interactions, horticultural breeding, and agricultural performance. High-throughput phenotyping of colour is valuable for understanding plant biology and selecting for traits related to colour during plant breeding. Here we present ColourQuant, an automated high-throughput pipeline that allows users to extract colour phenotypes from images. This pipeline includes methods for colour phenotyping using mean pixel values, Gaussian density estimator of Lab colour, and the analysis of shape-independent colour patterning by circular deformation.
[ { "created": "Tue, 5 Mar 2019 03:55:24 GMT", "version": "v1" } ]
2019-03-06
[ [ "Li", "Mao", "" ], [ "Frank", "Margaret H.", "" ], [ "Migicovsky", "Zoë", "" ] ]
Colour patterning contributes to important plant traits that influence ecological interactions, horticultural breeding, and agricultural performance. High-throughput phenotyping of colour is valuable for understanding plant biology and selecting for traits related to colour during plant breeding. Here we present ColourQuant, an automated high-throughput pipeline that allows users to extract colour phenotypes from images. This pipeline includes methods for colour phenotyping using mean pixel values, Gaussian density estimator of Lab colour, and the analysis of shape-independent colour patterning by circular deformation.
q-bio/0411053
Ralf Metzler
Tobias Ambjornsson and Ralf Metzler
Coupled dynamics of DNA-breathing and single-stranded DNA binding proteins
REVTeX4, 4 pages, 5 figures, revised version
null
null
null
q-bio.BM cond-mat.stat-mech
null
We study the size fluctuations of a local denaturation zone in a DNA molecule in the presence of proteins that selectively bind to single-stranded DNA, based on a (2+1)-dimensional master equation. By tuning the physical parameters we can drive the system from undisturbed bubble fluctuations to full, binding protein-induced denaturation. We determine the effective free energy landscape of the DNA-bubble and explore its relaxation modes.
[ { "created": "Tue, 30 Nov 2004 13:06:58 GMT", "version": "v1" }, { "created": "Fri, 17 Jun 2005 10:57:06 GMT", "version": "v2" } ]
2007-05-23
[ [ "Ambjornsson", "Tobias", "" ], [ "Metzler", "Ralf", "" ] ]
We study the size fluctuations of a local denaturation zone in a DNA molecule in the presence of proteins that selectively bind to single-stranded DNA, based on a (2+1)-dimensional master equation. By tuning the physical parameters we can drive the system from undisturbed bubble fluctuations to full, binding protein-induced denaturation. We determine the effective free energy landscape of the DNA-bubble and explore its relaxation modes.
1902.09360
Les Hatton
Les Hatton, Gregory Warr
CoHSI V: Identical multiple scale-independent systems within genomes and computer software
22 pages, 13 figures, 35 references
null
null
null
q-bio.OT
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
A mechanism-free and symbol-agnostic conservation principle, the Conservation of Hartley-Shannon Information (CoHSI) is predicted to constrain the structure of discrete systems regardless of their origin or function. Despite their distinct provenance, genomes and computer software share a simple structural property; they are linear symbol-based discrete systems, and thus they present an opportunity to test in a comparative context the predictions of CoHSI. Here, without any consideration of, or relevance to, their role in specifying function, we identify that 10 representative genomes (from microbes to human) and a large collection of software contain identically structured nested subsystems. In the case of base sequences in genomes, CoHSI predicts that if we split the genome into n-tuples (a 2-tuple is a pair of consecutive bases; a 3-tuple is a trio and so on), without regard for whether or not a region is coding, then each collection of n-tuples will constitute a homogeneous discrete system and will obey a power-law in frequency of occurrence of the n-tuples. We consider 1-, 2-, 3-, 4-, 5-, 6-, 7- and 8-tuples of ten species and demonstrate that the predicted power-law behavior is emphatically present, and furthermore as predicted, is insensitive to the start window for the tuple extraction i.e. the reading frame is irrelevant. We go on to provide a proof of Chargaff's second parity rule and on the basis of this proof, predict higher order tuple parity rules which we then identify in the genome data. CoHSI predicts precisely the same behavior in computer software. This prediction was tested and confirmed using 2-, 3- and 4-tuples of the hexadecimal representation of machine code in multiple computer programs, underlining the fundamental role played by CoHSI in defining the landscape in which discrete symbol-based systems must operate.
[ { "created": "Mon, 25 Feb 2019 15:24:22 GMT", "version": "v1" } ]
2019-02-26
[ [ "Hatton", "Les", "" ], [ "Warr", "Gregory", "" ] ]
A mechanism-free and symbol-agnostic conservation principle, the Conservation of Hartley-Shannon Information (CoHSI) is predicted to constrain the structure of discrete systems regardless of their origin or function. Despite their distinct provenance, genomes and computer software share a simple structural property; they are linear symbol-based discrete systems, and thus they present an opportunity to test in a comparative context the predictions of CoHSI. Here, without any consideration of, or relevance to, their role in specifying function, we identify that 10 representative genomes (from microbes to human) and a large collection of software contain identically structured nested subsystems. In the case of base sequences in genomes, CoHSI predicts that if we split the genome into n-tuples (a 2-tuple is a pair of consecutive bases; a 3-tuple is a trio and so on), without regard for whether or not a region is coding, then each collection of n-tuples will constitute a homogeneous discrete system and will obey a power-law in frequency of occurrence of the n-tuples. We consider 1-, 2-, 3-, 4-, 5-, 6-, 7- and 8-tuples of ten species and demonstrate that the predicted power-law behavior is emphatically present, and furthermore as predicted, is insensitive to the start window for the tuple extraction i.e. the reading frame is irrelevant. We go on to provide a proof of Chargaff's second parity rule and on the basis of this proof, predict higher order tuple parity rules which we then identify in the genome data. CoHSI predicts precisely the same behavior in computer software. This prediction was tested and confirmed using 2-, 3- and 4-tuples of the hexadecimal representation of machine code in multiple computer programs, underlining the fundamental role played by CoHSI in defining the landscape in which discrete symbol-based systems must operate.
2301.07386
Lingbin Bian
Lingbin Bian, Nizhuan Wang, Leonardo Novelli, Jonathan Keith, and Adeel Razi
Hierarchical Bayesian inference for community detection and connectivity of functional brain networks
null
null
null
null
q-bio.NC stat.AP
http://creativecommons.org/licenses/by/4.0/
Many functional magnetic resonance imaging (fMRI) studies rely on estimates of hierarchically organised brain networks whose segregation and integration reflect the dynamic transitions of latent cognitive states. However, most existing methods for estimating the community structure of networks from both individual and group-level analysis neglect the variability between subjects and lack validation. In this paper, we develop a new multilayer community detection method based on Bayesian latent block modelling. The method can robustly detect the group-level community structure of weighted functional networks that give rise to hidden brain states with an unknown number of communities and retain the variability of individual networks. For validation, we propose a new community structure-based multivariate Gaussian generative model to simulate synthetic signal. Our result shows that the inferred community memberships using hierarchical Bayesian analysis are consistent with the predefined node labels in the generative model. The method is also tested using real working memory task-fMRI data of 100 unrelated healthy subjects from the Human Connectome Project. The results show distinctive community structure patterns between 2-back, 0-back, and fixation conditions, which may reflect cognitive and behavioural states under working memory task conditions.
[ { "created": "Wed, 18 Jan 2023 09:30:46 GMT", "version": "v1" }, { "created": "Sun, 26 May 2024 13:34:59 GMT", "version": "v2" } ]
2024-05-28
[ [ "Bian", "Lingbin", "" ], [ "Wang", "Nizhuan", "" ], [ "Novelli", "Leonardo", "" ], [ "Keith", "Jonathan", "" ], [ "Razi", "Adeel", "" ] ]
Many functional magnetic resonance imaging (fMRI) studies rely on estimates of hierarchically organised brain networks whose segregation and integration reflect the dynamic transitions of latent cognitive states. However, most existing methods for estimating the community structure of networks from both individual and group-level analysis neglect the variability between subjects and lack validation. In this paper, we develop a new multilayer community detection method based on Bayesian latent block modelling. The method can robustly detect the group-level community structure of weighted functional networks that give rise to hidden brain states with an unknown number of communities and retain the variability of individual networks. For validation, we propose a new community structure-based multivariate Gaussian generative model to simulate synthetic signal. Our result shows that the inferred community memberships using hierarchical Bayesian analysis are consistent with the predefined node labels in the generative model. The method is also tested using real working memory task-fMRI data of 100 unrelated healthy subjects from the Human Connectome Project. The results show distinctive community structure patterns between 2-back, 0-back, and fixation conditions, which may reflect cognitive and behavioural states under working memory task conditions.
2106.05388
Jiabin Tang
Jiabin Tang, Shivani Patel, Steve Gentleman, Paul Matthews
Neurological Consequences of COVID-19 Infection
19 pages, 4 figures
null
null
null
q-bio.NC q-bio.MN
http://creativecommons.org/licenses/by/4.0/
COVID-19 infections have well described systemic manifestations, especially respiratory problems. There are currently no specific treatments or vaccines against the current strain. With higher case numbers, a range of neurological symptoms are becoming apparent. The mechanisms responsible for these are not well defined, other than those related to hypoxia and microthrombi. We speculate that sustained systemic immune activation seen with SARS-CoV-2 may also cause secondary autoimmune activation in the CNS. Patients with chronic neurological diseases may be at higher risk because of chronic secondary respiratory disease and potentially poor nutritional status. Here, we review the impact of COVID-19 on people with chronic neurological diseases and potential mechanisms. We believe special attention to protecting people with neurodegenerative disease is warranted. We are concerned about a possible delayed pandemic in the form of an increased burden of neurodegenerative disease after acceleration of pathology by systemic COVID-19 infections.
[ { "created": "Wed, 9 Jun 2021 21:02:12 GMT", "version": "v1" } ]
2021-06-11
[ [ "Tang", "Jiabin", "" ], [ "Patel", "Shivani", "" ], [ "Gentleman", "Steve", "" ], [ "Matthews", "Paul", "" ] ]
COVID-19 infections have well described systemic manifestations, especially respiratory problems. There are currently no specific treatments or vaccines against the current strain. With higher case numbers, a range of neurological symptoms are becoming apparent. The mechanisms responsible for these are not well defined, other than those related to hypoxia and microthrombi. We speculate that sustained systemic immune activation seen with SARS-CoV-2 may also cause secondary autoimmune activation in the CNS. Patients with chronic neurological diseases may be at higher risk because of chronic secondary respiratory disease and potentially poor nutritional status. Here, we review the impact of COVID-19 on people with chronic neurological diseases and potential mechanisms. We believe special attention to protecting people with neurodegenerative disease is warranted. We are concerned about a possible delayed pandemic in the form of an increased burden of neurodegenerative disease after acceleration of pathology by systemic COVID-19 infections.
1907.00247
Jude Kong
Jude D. Kong, Hao Wang, Tariq Siddique, Julia Foght, Kathleen Semple, Zvonko Burkus, and Mark A. Lewis
Second-generation stoichiometric mathematical model to predict methane emissions from oil sands tailings
null
null
10.1016/j.scitotenv.2019.133645
null
q-bio.QM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Microbial metabolism of fugitive hydrocarbons produces greenhouse gas (GHG) emissions from oil sands tailings ponds (OSTP) and end pit lakes (EPL) that retain semisolid wastes from surface mining of oil sands ores. Predicting GHG production, particularly methane (CH4), would help oil sands operators mitigate tailings emissions and would assist regulators evaluating the trajectory of reclamation scenarios. Using empirical datasets from laboratory incubation of OSTP sediments with pertinent hydrocarbons, we developed a stoichiometric model for CH4 generation by indigenous microbes. This model improved on previous first-approximation models by considering long-term biodegradation kinetics for 18 relevant hydrocarbons from three different oil sands operations, lag times, nutrient limitations, and microbial growth and death rates. Laboratory measurements were used to estimate model parameter values and to validate the new model. Goodness of fit analysis showed that the stoichiometric model predicted CH4 production well; normalized mean square error analysis revealed that it surpassed previous models. Comparison of model predictions with field measurements of CH4 emissions further validated the new model. Importantly, the model also identified parameters that are currently lacking but are needed to enable future robust modeling of CH4 production from OSTP and EPL in situ.
[ { "created": "Sat, 29 Jun 2019 18:08:21 GMT", "version": "v1" } ]
2019-08-29
[ [ "Kong", "Jude D.", "" ], [ "Wang", "Hao", "" ], [ "Siddique", "Tariq", "" ], [ "Foght", "Julia", "" ], [ "Semple", "Kathleen", "" ], [ "Burkus", "Zvonko", "" ], [ "Lewis", "Mark A.", "" ] ]
Microbial metabolism of fugitive hydrocarbons produces greenhouse gas (GHG) emissions from oil sands tailings ponds (OSTP) and end pit lakes (EPL) that retain semisolid wastes from surface mining of oil sands ores. Predicting GHG production, particularly methane (CH4), would help oil sands operators mitigate tailings emissions and would assist regulators evaluating the trajectory of reclamation scenarios. Using empirical datasets from laboratory incubation of OSTP sediments with pertinent hydrocarbons, we developed a stoichiometric model for CH4 generation by indigenous microbes. This model improved on previous first-approximation models by considering long-term biodegradation kinetics for 18 relevant hydrocarbons from three different oil sands operations, lag times, nutrient limitations, and microbial growth and death rates. Laboratory measurements were used to estimate model parameter values and to validate the new model. Goodness of fit analysis showed that the stoichiometric model predicted CH4 production well; normalized mean square error analysis revealed that it surpassed previous models. Comparison of model predictions with field measurements of CH4 emissions further validated the new model. Importantly, the model also identified parameters that are currently lacking but are needed to enable future robust modeling of CH4 production from OSTP and EPL in situ.
0707.2076
Orion Penner
Orion Penner, Vishal Sood, Gabe Musso, Kim Baskerville, Peter Grassberger, Maya Paczuski
Node similarity within subgraphs of protein interaction networks
10 pages, 5 figures. Edited for typos, clarity, figures improved for readability
null
10.1016/j.physa.2008.02.043
null
q-bio.MN cond-mat.stat-mech
null
We propose a biologically motivated quantity, twinness, to evaluate local similarity between nodes in a network. The twinness of a pair of nodes is the number of connected, labeled subgraphs of size n in which the two nodes possess identical neighbours. The graph animal algorithm is used to estimate twinness for each pair of nodes (for subgraph sizes n=4 to n=12) in four different protein interaction networks (PINs). These include an Escherichia coli PIN and three Saccharomyces cerevisiae PINs -- each obtained using state-of-the-art high throughput methods. In almost all cases, the average twinness of node pairs is vastly higher than expected from a null model obtained by switching links. For all n, we observe a difference in the ratio of type A twins (which are unlinked pairs) to type B twins (which are linked pairs) distinguishing the prokaryote E. coli from the eukaryote S. cerevisiae. Interaction similarity is expected due to gene duplication, and whole genome duplication paralogues in S. cerevisiae have been reported to co-cluster into the same complexes. Indeed, we find that these paralogous proteins are over-represented as twins compared to pairs chosen at random. These results indicate that twinness can detect ancestral relationships from currently available PIN data.
[ { "created": "Fri, 13 Jul 2007 19:46:04 GMT", "version": "v1" }, { "created": "Fri, 17 Aug 2007 22:16:52 GMT", "version": "v2" } ]
2009-11-13
[ [ "Penner", "Orion", "" ], [ "Sood", "Vishal", "" ], [ "Musso", "Gabe", "" ], [ "Baskerville", "Kim", "" ], [ "Grassberger", "Peter", "" ], [ "Paczuski", "Maya", "" ] ]
We propose a biologically motivated quantity, twinness, to evaluate local similarity between nodes in a network. The twinness of a pair of nodes is the number of connected, labeled subgraphs of size n in which the two nodes possess identical neighbours. The graph animal algorithm is used to estimate twinness for each pair of nodes (for subgraph sizes n=4 to n=12) in four different protein interaction networks (PINs). These include an Escherichia coli PIN and three Saccharomyces cerevisiae PINs -- each obtained using state-of-the-art high throughput methods. In almost all cases, the average twinness of node pairs is vastly higher than expected from a null model obtained by switching links. For all n, we observe a difference in the ratio of type A twins (which are unlinked pairs) to type B twins (which are linked pairs) distinguishing the prokaryote E. coli from the eukaryote S. cerevisiae. Interaction similarity is expected due to gene duplication, and whole genome duplication paralogues in S. cerevisiae have been reported to co-cluster into the same complexes. Indeed, we find that these paralogous proteins are over-represented as twins compared to pairs chosen at random. These results indicate that twinness can detect ancestral relationships from currently available PIN data.
0708.0559
Eduardo Candelario-Jalil
E. Candelario-Jalil, D. Alvarez, N. Merino, O. S. Leon
Delayed treatment with nimesulide reduces measures of oxidative stress following global ischemic brain injury in gerbils
null
Neuroscience Research 47(2): 245-253 (2003)
null
null
q-bio.TO
null
Metabolism of arachidonic acid by cyclooxygenase is one of the primary sources of reactive oxygen species in the ischemic brain. Neuronal overexpression of cyclooxygenase-2 has recently been shown to contribute to neurodegeneration following ischemic injury. In the present study, we examined the possibility that the neuroprotective effects of the cyclooxygenase-2 inhibitor nimesulide would depend upon reduction of oxidative stress following cerebral ischemia. Gerbils were subjected to 5 min of transient global cerebral ischemia followed by 48 h of reperfusion and markers of oxidative stress were measured in hippocampus of gerbils receiving vehicle or nimesulide treatment at three different clinically relevant doses (3, 6 or 12 mg/kg). Compared with vehicle, nimesulide significantly (P<0.05) reduced hippocampal glutathione depletion and lipid peroxidation, as assessed by the levels of malondialdehyde (MDA), 4-hydroxy-alkenals (4-HDA) and lipid hydroperoxides levels, even when the treatment was delayed until 6 h after ischemia. Biochemical evidences of nimesulide neuroprotection were supported by histofluorescence findings using the novel marker of neuronal degeneration Fluoro-Jade B. Few Fluoro-Jade B positive cells were seen in CA1 region of hippocampus in ischemic animals treated with nimesulide compared with vehicle. These results suggest that nimesulide may protect neurons by attenuating oxidative stress and reperfusion injury following the ischemic insult with a wide therapeutic window of protection.
[ { "created": "Fri, 3 Aug 2007 18:23:38 GMT", "version": "v1" } ]
2007-08-06
[ [ "Candelario-Jalil", "E.", "" ], [ "Alvarez", "D.", "" ], [ "Merino", "N.", "" ], [ "Leon", "O. S.", "" ] ]
Metabolism of arachidonic acid by cyclooxygenase is one of the primary sources of reactive oxygen species in the ischemic brain. Neuronal overexpression of cyclooxygenase-2 has recently been shown to contribute to neurodegeneration following ischemic injury. In the present study, we examined the possibility that the neuroprotective effects of the cyclooxygenase-2 inhibitor nimesulide would depend upon reduction of oxidative stress following cerebral ischemia. Gerbils were subjected to 5 min of transient global cerebral ischemia followed by 48 h of reperfusion and markers of oxidative stress were measured in hippocampus of gerbils receiving vehicle or nimesulide treatment at three different clinically relevant doses (3, 6 or 12 mg/kg). Compared with vehicle, nimesulide significantly (P<0.05) reduced hippocampal glutathione depletion and lipid peroxidation, as assessed by the levels of malondialdehyde (MDA), 4-hydroxy-alkenals (4-HDA) and lipid hydroperoxides levels, even when the treatment was delayed until 6 h after ischemia. Biochemical evidences of nimesulide neuroprotection were supported by histofluorescence findings using the novel marker of neuronal degeneration Fluoro-Jade B. Few Fluoro-Jade B positive cells were seen in CA1 region of hippocampus in ischemic animals treated with nimesulide compared with vehicle. These results suggest that nimesulide may protect neurons by attenuating oxidative stress and reperfusion injury following the ischemic insult with a wide therapeutic window of protection.
2210.03198
James Brunner
James D. Brunner and Nicholas Chia
Metabolic Model-based Ecological Modeling for Probiotic Design
18 pages, 6 figures
null
null
null
q-bio.QM
http://creativecommons.org/licenses/by/4.0/
The microbial community composition in the human gut has a profound effect on human health. This observation has lead to extensive use of microbiome therapies, including over-the-counter ``probiotic" treatments intended to alter the composition of the microbiome. Despite so much promise and commercial interest, the factors that contribute to the success or failure of microbiome-targeted treatments remain unclear. We investigate the biotic interactions that lead to successful engraftment of a novel bacterial strain introduced to the microbiome as in probiotic treatments. We use pairwise genome-scale metabolic modeling with a generalized resource allocation constraint to build a network of interactions between 818 species with well developed models available in the AGORA database. We create induced sub-graphs using the taxa present in samples from three experimental engraftment studies and assess the likelihood of invader engraftment based on network structure. To do so, we use a set of dynamical models designed to reflect connect network topology to growth dynamics. We show that a generalized Lotka-Volterra model has strong ability to predict if a particular invader or probiotic will successfully engraft into an individual's microbiome. Furthermore, we show that the mechanistic nature of the model is useful for revealing which microbe-microbe interactions potentially drive engraftment.
[ { "created": "Thu, 6 Oct 2022 20:40:02 GMT", "version": "v1" } ]
2022-10-10
[ [ "Brunner", "James D.", "" ], [ "Chia", "Nicholas", "" ] ]
The microbial community composition in the human gut has a profound effect on human health. This observation has lead to extensive use of microbiome therapies, including over-the-counter ``probiotic" treatments intended to alter the composition of the microbiome. Despite so much promise and commercial interest, the factors that contribute to the success or failure of microbiome-targeted treatments remain unclear. We investigate the biotic interactions that lead to successful engraftment of a novel bacterial strain introduced to the microbiome as in probiotic treatments. We use pairwise genome-scale metabolic modeling with a generalized resource allocation constraint to build a network of interactions between 818 species with well developed models available in the AGORA database. We create induced sub-graphs using the taxa present in samples from three experimental engraftment studies and assess the likelihood of invader engraftment based on network structure. To do so, we use a set of dynamical models designed to reflect connect network topology to growth dynamics. We show that a generalized Lotka-Volterra model has strong ability to predict if a particular invader or probiotic will successfully engraft into an individual's microbiome. Furthermore, we show that the mechanistic nature of the model is useful for revealing which microbe-microbe interactions potentially drive engraftment.
2302.09670
Madhur Mangalam
Madhur Mangalam, Ralf Metzler, Damian G. Kelty-Stephen
Ergodic characterization of non-ergodic anomalous diffusion processes
24 pages; 10 figures
null
null
null
q-bio.QM
http://creativecommons.org/licenses/by-nc-nd/4.0/
Canonical characterization techniques that rely upon mean squared displacement ($\mathrm{MSD}$) break down for non-ergodic processes, making it challenging to characterize anomalous diffusion from an individual time-series measurement. Non-ergodicity reigns when the time-averaged mean square displacement $\mathrm{TA}$-$\mathrm{MSD}$ differs from the ensemble-averaged mean squared displacement $\mathrm{EA}$-$\mathrm{MSD}$ even in the limit of long measurement series. In these cases, the typical theoretical results for ensemble averages cannot be used to understand and interpret data acquired from time averages. The difficulty then lies in obtaining statistical descriptors of the measured diffusion process that are not non-ergodic. We show that linear descriptors such as the standard deviation ($SD$), coefficient of variation ($CV$), and root mean square ($RMS$) break ergodicity in proportion to non-ergodicity in the diffusion process. In contrast, time series of descriptors addressing sequential structure and its potential nonlinearity: multifractality change in a time-independent way and fulfill the ergodic assumption, largely independent of the time series' non-ergodicity. We show that these findings follow the multiplicative cascades underlying these diffusion processes. Adding fractal and multifractal descriptors to typical linear descriptors would improve the characterization of anomalous diffusion processes. Two particular points bear emphasis here. First, as an appropriate formalism for encoding the nonlinearity that might generate non-ergodicity, multifractal modeling offers descriptors that can behave ergodically enough to meet the needs of linear modeling. Second, this capacity to describe non-ergodic processes in ergodic terms offers the possibility that multifractal modeling could unify several disparate non-ergodic diffusion processes into a common framework.
[ { "created": "Sun, 19 Feb 2023 20:44:52 GMT", "version": "v1" } ]
2023-02-21
[ [ "Mangalam", "Madhur", "" ], [ "Metzler", "Ralf", "" ], [ "Kelty-Stephen", "Damian G.", "" ] ]
Canonical characterization techniques that rely upon mean squared displacement ($\mathrm{MSD}$) break down for non-ergodic processes, making it challenging to characterize anomalous diffusion from an individual time-series measurement. Non-ergodicity reigns when the time-averaged mean square displacement $\mathrm{TA}$-$\mathrm{MSD}$ differs from the ensemble-averaged mean squared displacement $\mathrm{EA}$-$\mathrm{MSD}$ even in the limit of long measurement series. In these cases, the typical theoretical results for ensemble averages cannot be used to understand and interpret data acquired from time averages. The difficulty then lies in obtaining statistical descriptors of the measured diffusion process that are not non-ergodic. We show that linear descriptors such as the standard deviation ($SD$), coefficient of variation ($CV$), and root mean square ($RMS$) break ergodicity in proportion to non-ergodicity in the diffusion process. In contrast, time series of descriptors addressing sequential structure and its potential nonlinearity: multifractality change in a time-independent way and fulfill the ergodic assumption, largely independent of the time series' non-ergodicity. We show that these findings follow the multiplicative cascades underlying these diffusion processes. Adding fractal and multifractal descriptors to typical linear descriptors would improve the characterization of anomalous diffusion processes. Two particular points bear emphasis here. First, as an appropriate formalism for encoding the nonlinearity that might generate non-ergodicity, multifractal modeling offers descriptors that can behave ergodically enough to meet the needs of linear modeling. Second, this capacity to describe non-ergodic processes in ergodic terms offers the possibility that multifractal modeling could unify several disparate non-ergodic diffusion processes into a common framework.
1802.05424
Sutapa Mukherji
Sutapa Mukherji
Threshold response and bistability in gene regulation by small noncoding RNA
19 pages
Eur. Phys. J. E (2018) 41: 2
null
null
q-bio.MN q-bio.CB
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
In this paper, we study through mathematical modelling the combined effect of transcriptional and translational regulation by proteins and small noncoding RNAs (sRNA) in a genetic feedback motif that has an important role in the survival of E.coli under stress associated with oxygen and energy availability. We show that subtle changes in this motif can bring in drastically different effects on the gene expression. In particular, we show that a threshold response in the gene expression changes to a bistable response as the regulation on sRNA synthesis or degradation is altered. These results are obtained under deterministic conditions. Next, we study how the gene expression is altered by additive and multiplicative noise which might arise due to probabilistic occurrences of different biochemical events. Using the Fokker-Planck formulation, we obtain steady state probability distributions for sRNA concentration for the network motifs displaying bistability. The probability distributions are found to be bimodal with two peaks at low and high concentrations of sRNAs. We further study the variations in the probability distributions under different values of noise strength and correlations. The results presented here might be of interest for designing synthetic network for artificial control.
[ { "created": "Thu, 15 Feb 2018 07:36:43 GMT", "version": "v1" } ]
2018-02-16
[ [ "Mukherji", "Sutapa", "" ] ]
In this paper, we study through mathematical modelling the combined effect of transcriptional and translational regulation by proteins and small noncoding RNAs (sRNA) in a genetic feedback motif that has an important role in the survival of E.coli under stress associated with oxygen and energy availability. We show that subtle changes in this motif can bring in drastically different effects on the gene expression. In particular, we show that a threshold response in the gene expression changes to a bistable response as the regulation on sRNA synthesis or degradation is altered. These results are obtained under deterministic conditions. Next, we study how the gene expression is altered by additive and multiplicative noise which might arise due to probabilistic occurrences of different biochemical events. Using the Fokker-Planck formulation, we obtain steady state probability distributions for sRNA concentration for the network motifs displaying bistability. The probability distributions are found to be bimodal with two peaks at low and high concentrations of sRNAs. We further study the variations in the probability distributions under different values of noise strength and correlations. The results presented here might be of interest for designing synthetic network for artificial control.
1404.6267
Octavio Miramontes
Octavio Miramontes and Og DeSouza
Social Evolution: New Horizons
16 pages 5 figures, chapter in forthcoming open access book "Frontiers in Ecology, Evolution and Complexity" CopIt-arXives 2014, Mexico
null
null
null
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Cooperation is a widespread natural phenomenon yet current evolutionary thinking is dominated by the paradigm of selfish competition. Recent advanced in many fronts of Biology and Non-linear Physics are helping to bring cooperation to its proper place. In this contribution, the most important controversies and open research avenues in the field of social evolution are reviewed. It is argued that a novel theory of social evolution must integrate the concepts of the science of Complex Systems with those of the Darwinian tradition. Current gene-centric approaches should be reviewed and com- plemented with evidence from multilevel phenomena (group selection), the constrains given by the non-linear nature of biological dynamical systems and the emergent nature of dissipative phenomena.
[ { "created": "Thu, 24 Apr 2014 21:00:14 GMT", "version": "v1" }, { "created": "Mon, 26 May 2014 19:55:23 GMT", "version": "v2" }, { "created": "Thu, 12 Jun 2014 16:28:56 GMT", "version": "v3" } ]
2014-06-13
[ [ "Miramontes", "Octavio", "" ], [ "DeSouza", "Og", "" ] ]
Cooperation is a widespread natural phenomenon yet current evolutionary thinking is dominated by the paradigm of selfish competition. Recent advanced in many fronts of Biology and Non-linear Physics are helping to bring cooperation to its proper place. In this contribution, the most important controversies and open research avenues in the field of social evolution are reviewed. It is argued that a novel theory of social evolution must integrate the concepts of the science of Complex Systems with those of the Darwinian tradition. Current gene-centric approaches should be reviewed and com- plemented with evidence from multilevel phenomena (group selection), the constrains given by the non-linear nature of biological dynamical systems and the emergent nature of dissipative phenomena.
2002.07873
Emily T Winn
Emily T. Winn, Marilyn Vazquez, Prachi Loliencar, Kaisa Taipale, Xu Wang and Giseon Heo
A survey of statistical learning techniques as applied to inexpensive pediatric Obstructive Sleep Apnea data
null
null
null
null
q-bio.QM cs.LG stat.AP stat.ML
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Pediatric obstructive sleep apnea affects an estimated 1-5% of elementary-school aged children and can lead to other detrimental health problems. Swift diagnosis and treatment are critical to a child's growth and development, but the variability of symptoms and the complexity of the available data make this a challenge. We take a first step in streamlining the process by focusing on inexpensive data from questionnaires and craniofacial measurements. We apply correlation networks, the Mapper algorithm from topological data analysis, and singular value decomposition in a process of exploratory data analysis. We then apply a variety of supervised and unsupervised learning techniques from statistics, machine learning, and topology, ranging from support vector machines to Bayesian classifiers and manifold learning. Finally, we analyze the results of each of these methods and discuss the implications for a multi-data-sourced algorithm moving forward.
[ { "created": "Mon, 17 Feb 2020 18:15:32 GMT", "version": "v1" }, { "created": "Fri, 21 Feb 2020 14:35:46 GMT", "version": "v2" }, { "created": "Sun, 8 Aug 2021 18:41:12 GMT", "version": "v3" } ]
2021-08-10
[ [ "Winn", "Emily T.", "" ], [ "Vazquez", "Marilyn", "" ], [ "Loliencar", "Prachi", "" ], [ "Taipale", "Kaisa", "" ], [ "Wang", "Xu", "" ], [ "Heo", "Giseon", "" ] ]
Pediatric obstructive sleep apnea affects an estimated 1-5% of elementary-school aged children and can lead to other detrimental health problems. Swift diagnosis and treatment are critical to a child's growth and development, but the variability of symptoms and the complexity of the available data make this a challenge. We take a first step in streamlining the process by focusing on inexpensive data from questionnaires and craniofacial measurements. We apply correlation networks, the Mapper algorithm from topological data analysis, and singular value decomposition in a process of exploratory data analysis. We then apply a variety of supervised and unsupervised learning techniques from statistics, machine learning, and topology, ranging from support vector machines to Bayesian classifiers and manifold learning. Finally, we analyze the results of each of these methods and discuss the implications for a multi-data-sourced algorithm moving forward.
0908.3946
Thierry Huillet
Thierry Huillet (LPTM)
Information and (co-)variances in discrete evolutionary genetics involving solely selection
a paraitre dans Journal of Statistical Mechanics: Theory and Applications
null
10.1088/1742-5468/2009/09/P09013
null
q-bio.QM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The purpose of this Note is twofold: First, we introduce the general formalism of evolutionary genetics dynamics involving fitnesses, under both the deterministic and stochastic setups, and chiefly in discrete-time. In the process, we particularize it to a one-parameter model where only a selection parameter is unknown. Then and in a parallel manner, we discuss the estimation problems of the selection parameter based on a single-generation frequency distribution shift under both deterministic and stochastic evolutionary dynamics. In the stochastics, we consider both the celebrated Wright-Fisher and Moran models.
[ { "created": "Thu, 27 Aug 2009 08:05:35 GMT", "version": "v1" } ]
2015-05-14
[ [ "Huillet", "Thierry", "", "LPTM" ] ]
The purpose of this Note is twofold: First, we introduce the general formalism of evolutionary genetics dynamics involving fitnesses, under both the deterministic and stochastic setups, and chiefly in discrete-time. In the process, we particularize it to a one-parameter model where only a selection parameter is unknown. Then and in a parallel manner, we discuss the estimation problems of the selection parameter based on a single-generation frequency distribution shift under both deterministic and stochastic evolutionary dynamics. In the stochastics, we consider both the celebrated Wright-Fisher and Moran models.
2201.10322
Christopher Thornton PhD
Christopher B Thornton, Niina Kolehmainen, Kianoush Nazarpour
Using unsupervised machine learning to quantify physical activity from accelerometry in a diverse and rapidly changing population
null
null
null
null
q-bio.QM
http://creativecommons.org/licenses/by/4.0/
Accelerometers are widely used to measure physical activity behaviour, including in children. The traditional method for processing acceleration data uses cut points to define physical activity intensity, relying on calibration studies that relate the magnitude of acceleration to energy expenditure. However, these relationships do not generalise across diverse populations and hence they must be parametrised for each subpopulation (e.g., age groups) which is costly and makes studies across diverse populations and over time difficult. A data driven approach that allows physical activity intensity states to emerge from the data, without relying on parameters derived from external populations, and offers a new perspective on this problem and potentially improved results. We applied an unsupervised machine learning approach, namely a hidden semi Markov model, to segment and cluster the accelerometer data recorded from 279 children (9 to 38 months old) with a diverse range of physical and social-cognitive abilities (measured using the Paediatric Evaluation of Disability Inventory). We benchmarked this analysis with the cut points approach calculated using the best available thresholds for the population. Time spent active as measured by this unsupervised approach correlated more strongly with measures of the childs mobility, social-cognitive capacity, independence, daily activity, and age than that measured using the cut points approach. Unsupervised machine learning offers the potential to provide a more sensitive, appropriate, and cost-effective approach to quantifying physical activity behaviour in diverse populations, compared to the current cut points approach. This, in turn, supports research that is more inclusive of diverse or rapidly changing populations.
[ { "created": "Tue, 25 Jan 2022 13:50:30 GMT", "version": "v1" }, { "created": "Sat, 19 Feb 2022 10:07:23 GMT", "version": "v2" } ]
2022-02-22
[ [ "Thornton", "Christopher B", "" ], [ "Kolehmainen", "Niina", "" ], [ "Nazarpour", "Kianoush", "" ] ]
Accelerometers are widely used to measure physical activity behaviour, including in children. The traditional method for processing acceleration data uses cut points to define physical activity intensity, relying on calibration studies that relate the magnitude of acceleration to energy expenditure. However, these relationships do not generalise across diverse populations and hence they must be parametrised for each subpopulation (e.g., age groups) which is costly and makes studies across diverse populations and over time difficult. A data driven approach that allows physical activity intensity states to emerge from the data, without relying on parameters derived from external populations, and offers a new perspective on this problem and potentially improved results. We applied an unsupervised machine learning approach, namely a hidden semi Markov model, to segment and cluster the accelerometer data recorded from 279 children (9 to 38 months old) with a diverse range of physical and social-cognitive abilities (measured using the Paediatric Evaluation of Disability Inventory). We benchmarked this analysis with the cut points approach calculated using the best available thresholds for the population. Time spent active as measured by this unsupervised approach correlated more strongly with measures of the childs mobility, social-cognitive capacity, independence, daily activity, and age than that measured using the cut points approach. Unsupervised machine learning offers the potential to provide a more sensitive, appropriate, and cost-effective approach to quantifying physical activity behaviour in diverse populations, compared to the current cut points approach. This, in turn, supports research that is more inclusive of diverse or rapidly changing populations.
2406.01501
Andrew Straw
Stephan Lochner, Daniel Honerkamp, Abhinav Valada, Andrew D. Straw
Reinforcement Learning as a Robotics-Inspired Framework for Insect Navigation: From Spatial Representations to Neural Implementation
26 pages, 5 figures; submitted to Frontiers in Computational Neuroscience
null
null
null
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Bees are among the master navigators of the insect world. Despite impressive advances in robot navigation research, the performance of these insects is still unrivaled by any artificial system in terms of training efficiency and generalization capabilities, particularly considering the limited computational capacity. On the other hand, computational principles underlying these extraordinary feats are still only partially understood. The theoretical framework of reinforcement learning (RL) provides an ideal focal point to bring the two fields together for mutual benefit. In particular, we analyze and compare representations of space in robot and insect navigation models through the lens of RL, as the efficiency of insect navigation is likely rooted in an efficient and robust internal representation, linking retinotopic (egocentric) visual input with the geometry of the environment. While RL has long been at the core of robot navigation research, current computational theories of insect navigation are not commonly formulated within this framework, but largely as an associative learning process implemented in the insect brain, especially in the mushroom body (MB). Here we propose specific hypothetical components of the MB circuit that would enable the implementation of a certain class of relatively simple RL algorithms, capable of integrating distinct components of a navigation task, reminiscent of hierarchical RL models used in robot navigation. We discuss how current models of insect and robot navigation are exploring representations beyond classical, complete map-like representations, with spatial information being embedded in the respective latent representations to varying degrees.
[ { "created": "Mon, 3 Jun 2024 16:28:09 GMT", "version": "v1" }, { "created": "Fri, 5 Jul 2024 11:04:39 GMT", "version": "v2" }, { "created": "Wed, 24 Jul 2024 16:28:10 GMT", "version": "v3" } ]
2024-07-25
[ [ "Lochner", "Stephan", "" ], [ "Honerkamp", "Daniel", "" ], [ "Valada", "Abhinav", "" ], [ "Straw", "Andrew D.", "" ] ]
Bees are among the master navigators of the insect world. Despite impressive advances in robot navigation research, the performance of these insects is still unrivaled by any artificial system in terms of training efficiency and generalization capabilities, particularly considering the limited computational capacity. On the other hand, computational principles underlying these extraordinary feats are still only partially understood. The theoretical framework of reinforcement learning (RL) provides an ideal focal point to bring the two fields together for mutual benefit. In particular, we analyze and compare representations of space in robot and insect navigation models through the lens of RL, as the efficiency of insect navigation is likely rooted in an efficient and robust internal representation, linking retinotopic (egocentric) visual input with the geometry of the environment. While RL has long been at the core of robot navigation research, current computational theories of insect navigation are not commonly formulated within this framework, but largely as an associative learning process implemented in the insect brain, especially in the mushroom body (MB). Here we propose specific hypothetical components of the MB circuit that would enable the implementation of a certain class of relatively simple RL algorithms, capable of integrating distinct components of a navigation task, reminiscent of hierarchical RL models used in robot navigation. We discuss how current models of insect and robot navigation are exploring representations beyond classical, complete map-like representations, with spatial information being embedded in the respective latent representations to varying degrees.
2103.00258
Dagmar Iber
Christine Lang, Lisa Conrad, Dagmar Iber
Organ-specific Branching Morphogenesis
null
null
null
null
q-bio.TO
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
A common developmental process, called branching morphogenesis, generates the epithelial trees in a variety of organs, including the lungs, kidneys, and glands. How branching morphogenesis can create epithelial architectures of very different shapes and functions remains elusive. In this review, we compare branching morphogenesis and its regulation in lungs and kidneys and discuss the role of signaling pathways, the mesenchyme, the extracellular matrix, and the cytoskeleton as potential organ-specific determinants of branch position, orientation, and shape. Identifying the determinants of branch and organ shape and their adaptation in different organs may reveal how a highly conserved developmental process can be adapted to different structural and functional frameworks and should provide important insights into epithelial morphogenesis and developmental disorders.
[ { "created": "Sat, 27 Feb 2021 16:02:53 GMT", "version": "v1" } ]
2021-03-02
[ [ "Lang", "Christine", "" ], [ "Conrad", "Lisa", "" ], [ "Iber", "Dagmar", "" ] ]
A common developmental process, called branching morphogenesis, generates the epithelial trees in a variety of organs, including the lungs, kidneys, and glands. How branching morphogenesis can create epithelial architectures of very different shapes and functions remains elusive. In this review, we compare branching morphogenesis and its regulation in lungs and kidneys and discuss the role of signaling pathways, the mesenchyme, the extracellular matrix, and the cytoskeleton as potential organ-specific determinants of branch position, orientation, and shape. Identifying the determinants of branch and organ shape and their adaptation in different organs may reveal how a highly conserved developmental process can be adapted to different structural and functional frameworks and should provide important insights into epithelial morphogenesis and developmental disorders.
1504.03802
Filippo Biscarini
Filippo Biscarini, Stefano Biffani and Alessandra Stella
M\'as all\'a del GWAS: alternativas para localizar QTLs
5 pages, 3 figures, article in Spanish with abstract both in Spanish and English
null
null
null
q-bio.GN
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Beyond GWAS: alternatives to localize QTLs in farm animals. Two methods that could be used for QTL mapping as alternatives to standard GWAS are presented. The first relies on the differential frequency of runs of homozygosity (ROH) in groups of animals (e.g. cases and controls), while the second stems from resampling techniques used for the prediction of carriers of a mutation, and is based on the frequency of inclusion of polymorphisms (SNP) in the predictive model. ROH were applied to the detection of reproductive diseases in Holstein-Friesian cattle, while resampling was applied to the detection of carriers of the BH2 haplotype in Brown Swiss cattle. These alternative approaches may complement GWAS analyses in localizing more accurately QTLs for traits of interest in livestock.
[ { "created": "Wed, 15 Apr 2015 07:24:34 GMT", "version": "v1" } ]
2015-04-16
[ [ "Biscarini", "Filippo", "" ], [ "Biffani", "Stefano", "" ], [ "Stella", "Alessandra", "" ] ]
Beyond GWAS: alternatives to localize QTLs in farm animals. Two methods that could be used for QTL mapping as alternatives to standard GWAS are presented. The first relies on the differential frequency of runs of homozygosity (ROH) in groups of animals (e.g. cases and controls), while the second stems from resampling techniques used for the prediction of carriers of a mutation, and is based on the frequency of inclusion of polymorphisms (SNP) in the predictive model. ROH were applied to the detection of reproductive diseases in Holstein-Friesian cattle, while resampling was applied to the detection of carriers of the BH2 haplotype in Brown Swiss cattle. These alternative approaches may complement GWAS analyses in localizing more accurately QTLs for traits of interest in livestock.
2306.03603
Christos Sourmpis
Christos Sourmpis, Carl Petersen, Wulfram Gerstner, Guillaume Bellec
Trial matching: capturing variability with data-constrained spiking neural networks
12 pages of main text, 4 figures in main, 5 pages of appendix, 5 figures in appendix
null
null
null
q-bio.NC
http://creativecommons.org/licenses/by/4.0/
Simultaneous behavioral and electrophysiological recordings call for new methods to reveal the interactions between neural activity and behavior. A milestone would be an interpretable model of the co-variability of spiking activity and behavior across trials. Here, we model a mouse cortical sensory-motor pathway in a tactile detection task reported by licking with a large recurrent spiking neural network (RSNN), fitted to the recordings via gradient-based optimization. We focus specifically on the difficulty to match the trial-to-trial variability in the data. Our solution relies on optimal transport to define a distance between the distributions of generated and recorded trials. The technique is applied to artificial data and neural recordings covering six cortical areas. We find that the resulting RSNN can generate realistic cortical activity and predict jaw movements across the main modes of trial-to-trial variability. Our analysis also identifies an unexpected mode of variability in the data corresponding to task-irrelevant movements of the mouse.
[ { "created": "Tue, 6 Jun 2023 11:46:31 GMT", "version": "v1" }, { "created": "Fri, 1 Dec 2023 16:41:24 GMT", "version": "v2" } ]
2023-12-04
[ [ "Sourmpis", "Christos", "" ], [ "Petersen", "Carl", "" ], [ "Gerstner", "Wulfram", "" ], [ "Bellec", "Guillaume", "" ] ]
Simultaneous behavioral and electrophysiological recordings call for new methods to reveal the interactions between neural activity and behavior. A milestone would be an interpretable model of the co-variability of spiking activity and behavior across trials. Here, we model a mouse cortical sensory-motor pathway in a tactile detection task reported by licking with a large recurrent spiking neural network (RSNN), fitted to the recordings via gradient-based optimization. We focus specifically on the difficulty to match the trial-to-trial variability in the data. Our solution relies on optimal transport to define a distance between the distributions of generated and recorded trials. The technique is applied to artificial data and neural recordings covering six cortical areas. We find that the resulting RSNN can generate realistic cortical activity and predict jaw movements across the main modes of trial-to-trial variability. Our analysis also identifies an unexpected mode of variability in the data corresponding to task-irrelevant movements of the mouse.
1004.1378
Sebastian Risau-Gusman
Sebastian Risau-Gusman
Influence of network dynamics on the spread of sexually transmitted diseases
21 pages
null
null
null
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Network epidemiology often assumes that the relationships defining the social network of a population are static. The dynamics of relationships is only taken indirectly into account, by assuming that the relevant information to study epidemic spread is encoded in the network obtained by considering numbers of partners accumulated over periods of time roughly proportional to the infectious period of the disease at hand. On the other hand, models explicitly including social dynamics are often too schematic to provide a reasonable representation of a real population, or so detailed that no general conclusions can be drawn from them. Here we present a model of social dynamics that is general enough that its parameters can be obtained by fitting data from surveys about sexual behaviour, but that can still be studied analytically, using mean field techniques. This allows us to obtain some general results about epidemic spreading. We show that using accumulated network data to estimate the static epidemic threshold leads to a significant underestimation of it. We also show that, for a dynamic network, the relative epidemic threshold is an increasing function of the infectious period of the disease, implying that the static value is a lower bound to the real threshold.
[ { "created": "Thu, 8 Apr 2010 17:29:52 GMT", "version": "v1" } ]
2010-04-09
[ [ "Risau-Gusman", "Sebastian", "" ] ]
Network epidemiology often assumes that the relationships defining the social network of a population are static. The dynamics of relationships is only taken indirectly into account, by assuming that the relevant information to study epidemic spread is encoded in the network obtained by considering numbers of partners accumulated over periods of time roughly proportional to the infectious period of the disease at hand. On the other hand, models explicitly including social dynamics are often too schematic to provide a reasonable representation of a real population, or so detailed that no general conclusions can be drawn from them. Here we present a model of social dynamics that is general enough that its parameters can be obtained by fitting data from surveys about sexual behaviour, but that can still be studied analytically, using mean field techniques. This allows us to obtain some general results about epidemic spreading. We show that using accumulated network data to estimate the static epidemic threshold leads to a significant underestimation of it. We also show that, for a dynamic network, the relative epidemic threshold is an increasing function of the infectious period of the disease, implying that the static value is a lower bound to the real threshold.
1806.11066
Cedric Perret
Cedric Perret, Simon T. Powers, Jeremy Pitt and Emma Hart
Can justice be fair when it is blind? How social network structures can promote or prevent the evolution of despotism
To appear in Proceedings of the Artificial Life Conference 2018 (ALIFE 2018), MIT Press
null
null
null
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Hierarchy is an efficient way for a group to organize, but often goes along with inequality that benefits leaders. To control despotic behaviour, followers can assess leaders decisions by aggregating their own and their neighbours experience, and in response challenge despotic leaders. But in hierarchical social networks, this interactional justice can be limited by (i) the high influence of a small clique who are treated better, and (ii) the low connectedness of followers. Here we study how the connectedness of a social network affects the co-evolution of despotism in leaders and tolerance to despotism in followers. We simulate the evolution of a population of agents, where the influence of an agent is its number of social links. Whether a leader remains in power is controlled by the overall satisfaction of group members, as determined by their joint assessment of the leaders behaviour. We demonstrate that centralization of a social network around a highly influential clique greatly increases the level of despotism. This is because the clique is more satisfied, and their higher influence spreads their positive opinion of the leader throughout the network. Finally, our results suggest that increasing the connectedness of followers limits despotism while maintaining hierarchy.
[ { "created": "Thu, 28 Jun 2018 16:32:02 GMT", "version": "v1" } ]
2018-06-29
[ [ "Perret", "Cedric", "" ], [ "Powers", "Simon T.", "" ], [ "Pitt", "Jeremy", "" ], [ "Hart", "Emma", "" ] ]
Hierarchy is an efficient way for a group to organize, but often goes along with inequality that benefits leaders. To control despotic behaviour, followers can assess leaders decisions by aggregating their own and their neighbours experience, and in response challenge despotic leaders. But in hierarchical social networks, this interactional justice can be limited by (i) the high influence of a small clique who are treated better, and (ii) the low connectedness of followers. Here we study how the connectedness of a social network affects the co-evolution of despotism in leaders and tolerance to despotism in followers. We simulate the evolution of a population of agents, where the influence of an agent is its number of social links. Whether a leader remains in power is controlled by the overall satisfaction of group members, as determined by their joint assessment of the leaders behaviour. We demonstrate that centralization of a social network around a highly influential clique greatly increases the level of despotism. This is because the clique is more satisfied, and their higher influence spreads their positive opinion of the leader throughout the network. Finally, our results suggest that increasing the connectedness of followers limits despotism while maintaining hierarchy.
1007.4527
Tsvi Tlusty
Yonatan Savir and Tsvi Tlusty
Optimal Design of a Molecular Recognizer: Molecular Recognition as a Bayesian Signal Detection Problem
Bayesian detection, conformational changes, molecular recognition, specificity. http://www.weizmann.ac.il/complex/tlusty/papers/IEEE2008.pdf
IEEE Journal of Selected Topics in Signal Processing, vol. 2, issue 3, pp. 390-399, 2008
10.1109/JSTSP.2008.923859
null
q-bio.MN cs.IT math.IT physics.bio-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Numerous biological functions-such as enzymatic catalysis, the immune response system, and the DNA-protein regulatory network-rely on the ability of molecules to specifically recognize target molecules within a large pool of similar competitors in a noisy biochemical environment. Using the basic framework of signal detection theory, we treat the molecular recognition process as a signal detection problem and examine its overall performance. Thus, we evaluate the optimal properties of a molecular recognizer in the presence of competition and noise. Our analysis reveals that the optimal design undergoes a "phase transition" as the structural properties of the molecules and interaction energies between them vary. In one phase, the recognizer should be complementary in structure to its target (like a lock and a key), while in the other, conformational changes upon binding, which often accompany molecular recognition, enhance recognition quality. Using this framework, the abundance of conformational changes may be explained as a result of increasing the fitness of the recognizer. Furthermore, this analysis may be used in future design of artificial signal processing devices based on biomolecules.
[ { "created": "Mon, 26 Jul 2010 18:19:13 GMT", "version": "v1" } ]
2010-07-27
[ [ "Savir", "Yonatan", "" ], [ "Tlusty", "Tsvi", "" ] ]
Numerous biological functions-such as enzymatic catalysis, the immune response system, and the DNA-protein regulatory network-rely on the ability of molecules to specifically recognize target molecules within a large pool of similar competitors in a noisy biochemical environment. Using the basic framework of signal detection theory, we treat the molecular recognition process as a signal detection problem and examine its overall performance. Thus, we evaluate the optimal properties of a molecular recognizer in the presence of competition and noise. Our analysis reveals that the optimal design undergoes a "phase transition" as the structural properties of the molecules and interaction energies between them vary. In one phase, the recognizer should be complementary in structure to its target (like a lock and a key), while in the other, conformational changes upon binding, which often accompany molecular recognition, enhance recognition quality. Using this framework, the abundance of conformational changes may be explained as a result of increasing the fitness of the recognizer. Furthermore, this analysis may be used in future design of artificial signal processing devices based on biomolecules.
1510.00767
Justin Yeakel
Justin D. Yeakel, Uttam Bhat, Emma A. Elliott Smith, Seth D. Newsome
Exploring the isotopic niche: isotopic variance, physiological incorporation, and the temporal dynamics of foraging
27 pages, 9 figures
null
10.3389/fevo.2016.00001
null
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Consumer foraging behaviors are dynamic, changing in response to prey availability, seasonality, competition, and even the consumer's physiological state. The isotopic composition of a consumer is a product of these factors as well as the isotopic 'landscape' of its prey, i.e. the isotopic mixing space. Here we build a mechanistic framework that links the ecological and physiological processes of an individual consumer to the isotopic distribution that describes its diet, and ultimately to the isotopic composition of its own tissues, defined as its 'isotopic niche'. By coupling these processes, we systematically investigate under what conditions the isotopic niche of a consumer changes as a function of both the geometric properties of its mixing space and foraging strategies that may be static or dynamic over time. Results of our derivations reveal general insight into the conditions impacting isotopic niche width as a function of consumer specialization on prey, as well as the consumer's ability to transition between diets over time. We show analytically that moderate specialization on isotopically unique prey can serve to maximize a consumer's isotopic niche width, while temporally dynamic diets will tend to result in peak isotopic variance during dietary transitions. We demonstrate the relevance of our theoretical findings by examining a marine system composed of nine invertebrate species commonly consumed by sea otters. In general, our analytical framework highlights the complex interplay of mixing space geometry and consumer dietary behavior in driving expansion and contraction of the isotopic niche. Because this approach is established on ecological mechanism, it is well-suited for enhancing the ecological interpretation, and uncovering the root causes, of observed isotopic data.
[ { "created": "Sat, 3 Oct 2015 02:32:59 GMT", "version": "v1" }, { "created": "Mon, 25 Jan 2016 21:11:08 GMT", "version": "v2" } ]
2016-02-12
[ [ "Yeakel", "Justin D.", "" ], [ "Bhat", "Uttam", "" ], [ "Smith", "Emma A. Elliott", "" ], [ "Newsome", "Seth D.", "" ] ]
Consumer foraging behaviors are dynamic, changing in response to prey availability, seasonality, competition, and even the consumer's physiological state. The isotopic composition of a consumer is a product of these factors as well as the isotopic 'landscape' of its prey, i.e. the isotopic mixing space. Here we build a mechanistic framework that links the ecological and physiological processes of an individual consumer to the isotopic distribution that describes its diet, and ultimately to the isotopic composition of its own tissues, defined as its 'isotopic niche'. By coupling these processes, we systematically investigate under what conditions the isotopic niche of a consumer changes as a function of both the geometric properties of its mixing space and foraging strategies that may be static or dynamic over time. Results of our derivations reveal general insight into the conditions impacting isotopic niche width as a function of consumer specialization on prey, as well as the consumer's ability to transition between diets over time. We show analytically that moderate specialization on isotopically unique prey can serve to maximize a consumer's isotopic niche width, while temporally dynamic diets will tend to result in peak isotopic variance during dietary transitions. We demonstrate the relevance of our theoretical findings by examining a marine system composed of nine invertebrate species commonly consumed by sea otters. In general, our analytical framework highlights the complex interplay of mixing space geometry and consumer dietary behavior in driving expansion and contraction of the isotopic niche. Because this approach is established on ecological mechanism, it is well-suited for enhancing the ecological interpretation, and uncovering the root causes, of observed isotopic data.
q-bio/0606043
Jiajia Dong
J.J. Dong, B.Schmittmann, and R.K.P.Zia
Towards a model for protein production rates
8 pages, 8 figures; This submission is a duplicate of arXiv:q-bio/0602024, and has been removed
Journal of Statistical Physics, Volume 128, Numbers 1-2 / July, 2007
10.1007/s10955-006-9134-7
null
q-bio.QM
null
This submission is a duplicate of arXiv:q-bio/0602024 and has been removed.
[ { "created": "Fri, 30 Jun 2006 15:53:36 GMT", "version": "v1" } ]
2007-08-02
[ [ "Dong", "J. J.", "" ], [ "Schmittmann", "B.", "" ], [ "Zia", "R. K. P.", "" ] ]
This submission is a duplicate of arXiv:q-bio/0602024 and has been removed.
2012.14192
Lucia Russo
Konstantinos Kaloudis, George A. Kevrekidis, Helena C. Maltezou, Cleo Anastassopoulou, Athanasios Tsakris, Lucia Russo
Estimation of the effective reproduction number for SARS-CoV-2 infection during the first epidemic wave in the metropolitan area of Athens, Greece
null
null
null
null
q-bio.PE physics.soc-ph stat.AP
http://creativecommons.org/licenses/by/4.0/
Herein, we provide estimations for the effective reproduction number $R_e$ for the greater metropolitan area of Athens, Greece during the first wave of the pandemic (February 26-May 15, 2020). For our calculations, we implemented, in a comparative approach, the two most widely used methods for the estimation of $R_e$, that by Wallinga and Teunis and by Cori et al. Data were retrieved from the national database of SARS-CoV-2 infections in Greece. Our analysis revealed that the expected value of Re dropped below 1 around March 15, shortly after the suspension of the operation of educational institutions of all levels nationwide on March 10, and the closing of all retail activities (cafes, bars, museums, shopping centres, sports facilities and restaurants) on March 13. On May 4, the date on which the gradual relaxation of the strict lockdown commenced, the expected value of $R_e$ was slightly below 1, however with relatively high levels of uncertainty due to the limited number of notified cases during this period. Finally, we discuss the limitations and pitfalls of the methods utilized for the estimation of the $R_e$, highlighting that the results of such analyses should be considered only as indicative by policy makers.
[ { "created": "Mon, 28 Dec 2020 11:08:51 GMT", "version": "v1" } ]
2020-12-29
[ [ "Kaloudis", "Konstantinos", "" ], [ "Kevrekidis", "George A.", "" ], [ "Maltezou", "Helena C.", "" ], [ "Anastassopoulou", "Cleo", "" ], [ "Tsakris", "Athanasios", "" ], [ "Russo", "Lucia", "" ] ]
Herein, we provide estimations for the effective reproduction number $R_e$ for the greater metropolitan area of Athens, Greece during the first wave of the pandemic (February 26-May 15, 2020). For our calculations, we implemented, in a comparative approach, the two most widely used methods for the estimation of $R_e$, that by Wallinga and Teunis and by Cori et al. Data were retrieved from the national database of SARS-CoV-2 infections in Greece. Our analysis revealed that the expected value of Re dropped below 1 around March 15, shortly after the suspension of the operation of educational institutions of all levels nationwide on March 10, and the closing of all retail activities (cafes, bars, museums, shopping centres, sports facilities and restaurants) on March 13. On May 4, the date on which the gradual relaxation of the strict lockdown commenced, the expected value of $R_e$ was slightly below 1, however with relatively high levels of uncertainty due to the limited number of notified cases during this period. Finally, we discuss the limitations and pitfalls of the methods utilized for the estimation of the $R_e$, highlighting that the results of such analyses should be considered only as indicative by policy makers.
2305.01941
Noelia Ferruz
Sergio Romero-Romero, Sebastian Lindner, Noelia Ferruz
Exploring the Protein Sequence Space with Global Generative Models
16 pages, 4 figures, 2 tables
null
null
null
q-bio.BM cs.LG
http://creativecommons.org/licenses/by-nc-sa/4.0/
Recent advancements in specialized large-scale architectures for training image and language have profoundly impacted the field of computer vision and natural language processing (NLP). Language models, such as the recent ChatGPT and GPT4 have demonstrated exceptional capabilities in processing, translating, and generating human languages. These breakthroughs have also been reflected in protein research, leading to the rapid development of numerous new methods in a short time, with unprecedented performance. Language models, in particular, have seen widespread use in protein research, as they have been utilized to embed proteins, generate novel ones, and predict tertiary structures. In this book chapter, we provide an overview of the use of protein generative models, reviewing 1) language models for the design of novel artificial proteins, 2) works that use non-Transformer architectures, and 3) applications in directed evolution approaches.
[ { "created": "Wed, 3 May 2023 07:45:29 GMT", "version": "v1" } ]
2023-05-04
[ [ "Romero-Romero", "Sergio", "" ], [ "Lindner", "Sebastian", "" ], [ "Ferruz", "Noelia", "" ] ]
Recent advancements in specialized large-scale architectures for training image and language have profoundly impacted the field of computer vision and natural language processing (NLP). Language models, such as the recent ChatGPT and GPT4 have demonstrated exceptional capabilities in processing, translating, and generating human languages. These breakthroughs have also been reflected in protein research, leading to the rapid development of numerous new methods in a short time, with unprecedented performance. Language models, in particular, have seen widespread use in protein research, as they have been utilized to embed proteins, generate novel ones, and predict tertiary structures. In this book chapter, we provide an overview of the use of protein generative models, reviewing 1) language models for the design of novel artificial proteins, 2) works that use non-Transformer architectures, and 3) applications in directed evolution approaches.
1209.0337
Antonio Freitas
Caroline Montaudouin, Marie Anson, Yi Hao, Susanne V. Duncker, Tahia Fernandez, Emmanuelle Gaudin, Michael Ehrenstein, William G. Kerr, Jean-Herve Colle, Pierre Bruhns, Marc Daeron, Antonio A. Freitas
Quorum sensing contributes to activated B cell homeostasis and to prevent autoimmunity
34 pages, 5 figures
null
null
null
q-bio.CB
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Maintenance of plasma IgM levels is critical for immune system function and homeostasis in humans and mice. However, the mechanisms that control homeostasis of the activated IgM-secreting B cells are unknown. After adoptive transfer into immune-deficient hosts, B-lymphocytes expand poorly but fully reconstitute the pool of natural IgM-secreting cells and circulating IgM levels. By using sequential cell transfers and B cell populations from several mutant mice, we were able to identify novel mechanisms regulating the size of the IgM-secreting B cell pool. Contrary to previous mechanisms described regulating homeostasis, which involve competition for the same niche by cells having overlapping survival requirements, homeostasis of the innate IgM-secreting B cell pool is also achieved when B cells populations are able to monitor the number of activated B cells by detecting their secreted products. Notably, B cell populations are able to assess the density of activated B cells by sensing their secreted IgG. This process involves the Fc{\gamma}RIIB, a low-affinity IgG receptor that is expressed on B cells and acts as a negative regulator of B cell activation, and its intracellular effector the inositol phosphatase SHIP. As a result of the engagement of this inhibitory pathway the number of activated IgM-secreting B cells is kept under control. We hypothesize that malfunction of this quorum-sensing mechanism may lead to uncontrolled B cell activation and autoimmunity.
[ { "created": "Mon, 3 Sep 2012 13:14:56 GMT", "version": "v1" } ]
2015-03-13
[ [ "Montaudouin", "Caroline", "" ], [ "Anson", "Marie", "" ], [ "Hao", "Yi", "" ], [ "Duncker", "Susanne V.", "" ], [ "Fernandez", "Tahia", "" ], [ "Gaudin", "Emmanuelle", "" ], [ "Ehrenstein", "Michael", "" ], [ "Kerr", "William G.", "" ], [ "Colle", "Jean-Herve", "" ], [ "Bruhns", "Pierre", "" ], [ "Daeron", "Marc", "" ], [ "Freitas", "Antonio A.", "" ] ]
Maintenance of plasma IgM levels is critical for immune system function and homeostasis in humans and mice. However, the mechanisms that control homeostasis of the activated IgM-secreting B cells are unknown. After adoptive transfer into immune-deficient hosts, B-lymphocytes expand poorly but fully reconstitute the pool of natural IgM-secreting cells and circulating IgM levels. By using sequential cell transfers and B cell populations from several mutant mice, we were able to identify novel mechanisms regulating the size of the IgM-secreting B cell pool. Contrary to previous mechanisms described regulating homeostasis, which involve competition for the same niche by cells having overlapping survival requirements, homeostasis of the innate IgM-secreting B cell pool is also achieved when B cells populations are able to monitor the number of activated B cells by detecting their secreted products. Notably, B cell populations are able to assess the density of activated B cells by sensing their secreted IgG. This process involves the Fc{\gamma}RIIB, a low-affinity IgG receptor that is expressed on B cells and acts as a negative regulator of B cell activation, and its intracellular effector the inositol phosphatase SHIP. As a result of the engagement of this inhibitory pathway the number of activated IgM-secreting B cells is kept under control. We hypothesize that malfunction of this quorum-sensing mechanism may lead to uncontrolled B cell activation and autoimmunity.
1305.1985
Jarrett Byrnes
Jarrett E. K. Byrnes, Lars Gamfeldt, Forest Isbell, Jonathan S. Lefcheck, John N. Griffin, Andrew Hector, Bradley J. Cardinale, David U. Hooper, Laura E. Dee, J. Emmett Duffy
Investigating the relationship between biodiversity and ecosystem multifunctionality: Challenges and solutions
This article has been submitted to Methods in Ecology & Evolution for review
null
10.1111/2041-210X.12143
null
q-bio.QM q-bio.PE stat.AP
http://creativecommons.org/licenses/by/3.0/
Extensive research shows that more species-rich assemblages are generally more productive and efficient in resource use than comparable assemblages with fewer species. But the question of how diversity simultaneously affects the wide variety of ecological functions that ecosystems perform remains relatively understudied, and it presents several analytical and empirical challenges that remain unresolved. In particular, researchers have developed several disparate metrics to quantify multifunctionality, each characterizing different aspects of the concept, and each with pros and cons. We compare four approaches to characterizing multifunctionality and its dependence on biodiversity, quantifying 1) magnitudes of multiple individual functions separately, 2) the extent to which different species promote different functions, 3) the average level of a suite of functions, and 4) the number of functions that simultaneously exceed a critical threshold. We illustrate each approach using data from the pan-European BIODEPTH experiment and the R multifunc package developed for this purpose, evaluate the strengths and weaknesses of each approach, and implement several methodological improvements. We conclude that a extension of the fourth approach that systematically explores all possible threshold values provides the most comprehensive description of multifunctionality to date. We outline this method and recommend its use in future research.
[ { "created": "Thu, 9 May 2013 01:08:37 GMT", "version": "v1" } ]
2014-01-28
[ [ "Byrnes", "Jarrett E. K.", "" ], [ "Gamfeldt", "Lars", "" ], [ "Isbell", "Forest", "" ], [ "Lefcheck", "Jonathan S.", "" ], [ "Griffin", "John N.", "" ], [ "Hector", "Andrew", "" ], [ "Cardinale", "Bradley J.", "" ], [ "Hooper", "David U.", "" ], [ "Dee", "Laura E.", "" ], [ "Duffy", "J. Emmett", "" ] ]
Extensive research shows that more species-rich assemblages are generally more productive and efficient in resource use than comparable assemblages with fewer species. But the question of how diversity simultaneously affects the wide variety of ecological functions that ecosystems perform remains relatively understudied, and it presents several analytical and empirical challenges that remain unresolved. In particular, researchers have developed several disparate metrics to quantify multifunctionality, each characterizing different aspects of the concept, and each with pros and cons. We compare four approaches to characterizing multifunctionality and its dependence on biodiversity, quantifying 1) magnitudes of multiple individual functions separately, 2) the extent to which different species promote different functions, 3) the average level of a suite of functions, and 4) the number of functions that simultaneously exceed a critical threshold. We illustrate each approach using data from the pan-European BIODEPTH experiment and the R multifunc package developed for this purpose, evaluate the strengths and weaknesses of each approach, and implement several methodological improvements. We conclude that a extension of the fourth approach that systematically explores all possible threshold values provides the most comprehensive description of multifunctionality to date. We outline this method and recommend its use in future research.
2401.10922
Rohan Nurani Rajagopal
Nurani Rajagopal Rohan, Sayan Gupta, V. Srinivasa Chakravarthy
A Chaotic Associative Memory
10 pages, 8 Figures, Submitted to "Chaos: An Interdisciplinary Journal of Nonlinear Science"
null
null
null
q-bio.NC nlin.CD
http://creativecommons.org/licenses/by/4.0/
We propose a novel Chaotic Associative Memory model using a network of chaotic Rossler systems and investigate the storage capacity and retrieval capabilities of this model as a function of increasing periodicity and chaos. In early models of associate memory networks, memories were modeled as fixed points, which may be mathematically convenient but has poor neurobiological plausibility. Since brain dynamics is inherently oscillatory, attempts have been made to construct associative memories using nonlinear oscillatory networks. However, oscillatory associative memories are plagued by the problem of poor storage capacity, though efforts have been made to improve capacity by adding higher order oscillatory modes. The chaotic associative memory proposed here exploits the continuous spectrum of chaotic elements and has higher storage capacity than previously described oscillatory associate memories.
[ { "created": "Mon, 15 Jan 2024 13:32:32 GMT", "version": "v1" } ]
2024-01-23
[ [ "Rohan", "Nurani Rajagopal", "" ], [ "Gupta", "Sayan", "" ], [ "Chakravarthy", "V. Srinivasa", "" ] ]
We propose a novel Chaotic Associative Memory model using a network of chaotic Rossler systems and investigate the storage capacity and retrieval capabilities of this model as a function of increasing periodicity and chaos. In early models of associate memory networks, memories were modeled as fixed points, which may be mathematically convenient but has poor neurobiological plausibility. Since brain dynamics is inherently oscillatory, attempts have been made to construct associative memories using nonlinear oscillatory networks. However, oscillatory associative memories are plagued by the problem of poor storage capacity, though efforts have been made to improve capacity by adding higher order oscillatory modes. The chaotic associative memory proposed here exploits the continuous spectrum of chaotic elements and has higher storage capacity than previously described oscillatory associate memories.
1411.2896
Carsten Conradi
Carsten Conradi and Maya Mincheva
Graph-theoretic analysis of multistationarity using degree theory
null
null
null
null
q-bio.MN math.DS
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Biochemical mechanisms with mass action kinetics are often modeled by systems of polynomial differential equations (DE). Determining directly if the DE system has multiple equilibria (multistationarity) is difficult for realistic systems, since they are large, nonlinear and contain many unknown parameters. Mass action biochemical mechanisms can be represented by a directed bipartite graph with species and reaction nodes. Graph-theoretic methods can then be used to assess the potential of a given biochemical mechanism for multistationarity by identifying structures in the bipartite graph referred to as critical fragments. In this article we present a graph-theoretic method for conservative biochemical mechanisms characterized by bounded species concentrations, which makes the use of degree theory arguments possible. We illustrate the results with an example of a MAPK network.
[ { "created": "Tue, 11 Nov 2014 17:38:25 GMT", "version": "v1" } ]
2014-11-12
[ [ "Conradi", "Carsten", "" ], [ "Mincheva", "Maya", "" ] ]
Biochemical mechanisms with mass action kinetics are often modeled by systems of polynomial differential equations (DE). Determining directly if the DE system has multiple equilibria (multistationarity) is difficult for realistic systems, since they are large, nonlinear and contain many unknown parameters. Mass action biochemical mechanisms can be represented by a directed bipartite graph with species and reaction nodes. Graph-theoretic methods can then be used to assess the potential of a given biochemical mechanism for multistationarity by identifying structures in the bipartite graph referred to as critical fragments. In this article we present a graph-theoretic method for conservative biochemical mechanisms characterized by bounded species concentrations, which makes the use of degree theory arguments possible. We illustrate the results with an example of a MAPK network.
1501.00302
Iddo Friedberg
David C Ream, Asma R Bankapur, Iddo Friedberg
An Event-Driven Approach for Studying Gene Block Evolution in Bacteria
Accepted in Bioinformatics (OUP)
null
null
null
q-bio.GN
http://creativecommons.org/licenses/by/3.0/
Motivation: Gene blocks are genes co-located on the chromosome. In many cases, genes blocks are conserved between bacterial species, sometimes as operons, when genes are co-transcribed. The conservation is rarely absolute: gene loss, gain, duplication, block splitting, and block fusion are frequently observed. An open question in bacterial molecular evolution is that of the formation and breakup of gene blocks, for which several models have been proposed. These models, however, are not generally applicable to all types of gene blocks, and consequently cannot be used to broadly compare and study gene block evolution. To address this problem we introduce an event-based method for tracking gene block evolution in bacteria. Results: We show here that the evolution of gene blocks in proteobacteria can be described by a small set of events. Those include the insertion of genes into, or the splitting of genes out of a gene block, gene loss, and gene duplication. We show how the event-based method of gene block evolution allows us to determine the evolutionary rate, and to trace the ancestral states of their formation. We conclude that the event-based method can be used to help us understand the formation of these important bacterial genomic structures. Availability: The software is available under GPLv3 license on http://github.com/reamdc1/gene_block_evolution.git Supplementary online material: http://iddo-friedberg.net/operon-evolution Contact: Iddo Friedberg i.friedberg@miamioh.edu
[ { "created": "Thu, 1 Jan 2015 19:47:22 GMT", "version": "v1" }, { "created": "Tue, 24 Feb 2015 23:25:39 GMT", "version": "v2" } ]
2015-02-26
[ [ "Ream", "David C", "" ], [ "Bankapur", "Asma R", "" ], [ "Friedberg", "Iddo", "" ] ]
Motivation: Gene blocks are genes co-located on the chromosome. In many cases, genes blocks are conserved between bacterial species, sometimes as operons, when genes are co-transcribed. The conservation is rarely absolute: gene loss, gain, duplication, block splitting, and block fusion are frequently observed. An open question in bacterial molecular evolution is that of the formation and breakup of gene blocks, for which several models have been proposed. These models, however, are not generally applicable to all types of gene blocks, and consequently cannot be used to broadly compare and study gene block evolution. To address this problem we introduce an event-based method for tracking gene block evolution in bacteria. Results: We show here that the evolution of gene blocks in proteobacteria can be described by a small set of events. Those include the insertion of genes into, or the splitting of genes out of a gene block, gene loss, and gene duplication. We show how the event-based method of gene block evolution allows us to determine the evolutionary rate, and to trace the ancestral states of their formation. We conclude that the event-based method can be used to help us understand the formation of these important bacterial genomic structures. Availability: The software is available under GPLv3 license on http://github.com/reamdc1/gene_block_evolution.git Supplementary online material: http://iddo-friedberg.net/operon-evolution Contact: Iddo Friedberg i.friedberg@miamioh.edu
1505.03558
Anna Melbinger
Anna Melbinger, Jonas Cremer and Erwin Frey
The Emergence of Cooperation from a Single Mutant during Microbial Life-Cycles
main text: 14 pages, 5 figures; supplement: 4 pages, figures
Journal of the Royal Society Interface (2015), Vol. 12, Issue: 108
10.1098/rsif.2015.0171
null
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Cooperative behavior is widespread in nature, even though cooperating individuals always run the risk to be exploited by free-riders. Population structure effectively promotes cooperation given that a threshold in the level of cooperation was already reached. However, the question how cooperation can emerge from a single mutant, which cannot rely on a benefit provided by other cooperators, is still puzzling. Here, we investigate this question for a well-defined but generic situation based on typical life-cycles of microbial populations where individuals regularly form new colonies followed by growth phases. We analyze two evolutionary mechanisms favoring cooperative behavior and study their strength depending on the inoculation size and the length of a life-cycle. In particular, we find that population bottlenecks followed by exponential growth phases strongly increase the survival and fixation probabilities of a single cooperator in a free-riding population.
[ { "created": "Wed, 13 May 2015 21:45:10 GMT", "version": "v1" }, { "created": "Sun, 14 Jun 2015 23:33:39 GMT", "version": "v2" } ]
2015-06-16
[ [ "Melbinger", "Anna", "" ], [ "Cremer", "Jonas", "" ], [ "Frey", "Erwin", "" ] ]
Cooperative behavior is widespread in nature, even though cooperating individuals always run the risk to be exploited by free-riders. Population structure effectively promotes cooperation given that a threshold in the level of cooperation was already reached. However, the question how cooperation can emerge from a single mutant, which cannot rely on a benefit provided by other cooperators, is still puzzling. Here, we investigate this question for a well-defined but generic situation based on typical life-cycles of microbial populations where individuals regularly form new colonies followed by growth phases. We analyze two evolutionary mechanisms favoring cooperative behavior and study their strength depending on the inoculation size and the length of a life-cycle. In particular, we find that population bottlenecks followed by exponential growth phases strongly increase the survival and fixation probabilities of a single cooperator in a free-riding population.
2006.08471
Piero Poletti
Piero Poletti, Marcello Tirani, Danilo Cereda, Filippo Trentini, Giorgio Guzzetta, Giuliana Sabatino, Valentina Marziano, Ambra Castrofino, Francesca Grosso, Gabriele Del Castillo, Raffaella Piccarreta, ATS Lombardy COVID-19 Task Force, Aida Andreassi, Alessia Melegaro, Maria Gramegna, Marco Ajelli, Stefano Merler
Probability of symptoms and critical disease after SARS-CoV-2 infection
sample increased: results updated with new records coming from the ongoing serological surveys
JAMA Netw Open. 2021;4(3):e211085
10.1001/jamanetworkopen.2021.1085
null
q-bio.PE
http://creativecommons.org/licenses/by-nc-sa/4.0/
We quantified the probability of developing symptoms (respiratory or fever \geq 37.5 {\deg}C) and critical disease (requiring intensive care or resulting in death) of SARS-CoV-2 positive subjects. 5,484 contacts of SARS-CoV-2 index cases detected in Lombardy, Italy were analyzed, and positive subjects were ascertained via nasal swabs and serological assays. 73.9% of all infected individuals aged less than 60 years did not develop symptoms (95% confidence interval: 71.8-75.9%). The risk of symptoms increased with age. 6.6% of infected subjects older than 60 years had critical disease, with males at significantly higher risk.
[ { "created": "Mon, 15 Jun 2020 15:21:06 GMT", "version": "v1" }, { "created": "Mon, 22 Jun 2020 12:22:55 GMT", "version": "v2" } ]
2022-02-21
[ [ "Poletti", "Piero", "" ], [ "Tirani", "Marcello", "" ], [ "Cereda", "Danilo", "" ], [ "Trentini", "Filippo", "" ], [ "Guzzetta", "Giorgio", "" ], [ "Sabatino", "Giuliana", "" ], [ "Marziano", "Valentina", "" ], [ "Castrofino", "Ambra", "" ], [ "Grosso", "Francesca", "" ], [ "Del Castillo", "Gabriele", "" ], [ "Piccarreta", "Raffaella", "" ], [ "Force", "ATS Lombardy COVID-19 Task", "" ], [ "Andreassi", "Aida", "" ], [ "Melegaro", "Alessia", "" ], [ "Gramegna", "Maria", "" ], [ "Ajelli", "Marco", "" ], [ "Merler", "Stefano", "" ] ]
We quantified the probability of developing symptoms (respiratory or fever \geq 37.5 {\deg}C) and critical disease (requiring intensive care or resulting in death) of SARS-CoV-2 positive subjects. 5,484 contacts of SARS-CoV-2 index cases detected in Lombardy, Italy were analyzed, and positive subjects were ascertained via nasal swabs and serological assays. 73.9% of all infected individuals aged less than 60 years did not develop symptoms (95% confidence interval: 71.8-75.9%). The risk of symptoms increased with age. 6.6% of infected subjects older than 60 years had critical disease, with males at significantly higher risk.
2112.07579
Tuul Sepp
Ciara Baines, Richard Meitern, Randel Kreitsberg, Tuul Sepp
Comparative study of the evolution of human cancer gene duplications across fish
31 pages, 5 figures. Submitted to Molecular Biology and Evolution
null
null
null
q-bio.PE q-bio.GN
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Comparative studies of cancer-related genes allow us to gain novel information about the evolution and function of these genes, but also to understand cancer as a driving force in biological systems and species life histories. So far, comparative studies of cancer genes have focused on mammals. Here, we provide the first comparative study of cancer-related gene copy number variation in fish. As fish are evolutionarily older and genetically more diverse than mammals, their tumour suppression mechanisms should not only include most of the mammalian mechanisms, but also reveal novel (but potentially phylogenetically older) previously undetected mechanisms. We have matched the sequenced genomes of 65 fish species from the Ensemble database with the cancer gene information from the COSMIC database. By calculating the number of gene copies across species using the Ensembl CAFE data (providing species trees for gene copy number counts), we were able to develop a novel, less resource demanding method for ortholog identification. Our analysis demonstrates a masked relationship with cancer-related gene copy number variation (CNV) and maximum lifespan in fish species, suggesting that higher tumour suppressor gene CNV lengthens and oncogene CNV shortens lifespan, when both traits are added to the model. Based on the correlation between tumour suppressor and oncogene CNV, we were able to show which species have more tumour suppressors in relation to oncogenes. It could therefore be suggested that these species have stronger genetic defences against oncogenic processes. Fish studies could yet be a largely unexplored treasure trove for understanding the evolution and ecology of cancer, by providing novel insights into the study of cancer and tumour suppression, in addition to the study of fish evolution, life-history trade-offs, and ecology.
[ { "created": "Tue, 14 Dec 2021 17:35:01 GMT", "version": "v1" } ]
2021-12-15
[ [ "Baines", "Ciara", "" ], [ "Meitern", "Richard", "" ], [ "Kreitsberg", "Randel", "" ], [ "Sepp", "Tuul", "" ] ]
Comparative studies of cancer-related genes allow us to gain novel information about the evolution and function of these genes, but also to understand cancer as a driving force in biological systems and species life histories. So far, comparative studies of cancer genes have focused on mammals. Here, we provide the first comparative study of cancer-related gene copy number variation in fish. As fish are evolutionarily older and genetically more diverse than mammals, their tumour suppression mechanisms should not only include most of the mammalian mechanisms, but also reveal novel (but potentially phylogenetically older) previously undetected mechanisms. We have matched the sequenced genomes of 65 fish species from the Ensemble database with the cancer gene information from the COSMIC database. By calculating the number of gene copies across species using the Ensembl CAFE data (providing species trees for gene copy number counts), we were able to develop a novel, less resource demanding method for ortholog identification. Our analysis demonstrates a masked relationship with cancer-related gene copy number variation (CNV) and maximum lifespan in fish species, suggesting that higher tumour suppressor gene CNV lengthens and oncogene CNV shortens lifespan, when both traits are added to the model. Based on the correlation between tumour suppressor and oncogene CNV, we were able to show which species have more tumour suppressors in relation to oncogenes. It could therefore be suggested that these species have stronger genetic defences against oncogenic processes. Fish studies could yet be a largely unexplored treasure trove for understanding the evolution and ecology of cancer, by providing novel insights into the study of cancer and tumour suppression, in addition to the study of fish evolution, life-history trade-offs, and ecology.
0707.3047
Alain Barrat
Aurelien Gautreau (LPT), Alain Barrat (LPT), Marc Barthelemy (DPTA)
Arrival Time Statistics in Global Disease Spread
null
J. Stat. Mech. (2007) L09001
10.1088/1742-5468/2007/09/L09001
null
q-bio.PE
null
Metapopulation models describing cities with different populations coupled by the travel of individuals are of great importance in the understanding of disease spread on a large scale. An important example is the Rvachev-Longini model [{\it Math. Biosci.} {\bf 75}, 3-22 (1985)] which is widely used in computational epidemiology. Few analytical results are however available and in particular little is known about paths followed by epidemics and disease arrival times. We study the arrival time of a disease in a city as a function of the starting seed of the epidemics. We propose an analytical Ansatz, test it in the case of a spreading on the world wide air transportation network, and show that it predicts accurately the arrival order of a disease in world-wide cities.
[ { "created": "Fri, 20 Jul 2007 11:45:42 GMT", "version": "v1" } ]
2007-09-19
[ [ "Gautreau", "Aurelien", "", "LPT" ], [ "Barrat", "Alain", "", "LPT" ], [ "Barthelemy", "Marc", "", "DPTA" ] ]
Metapopulation models describing cities with different populations coupled by the travel of individuals are of great importance in the understanding of disease spread on a large scale. An important example is the Rvachev-Longini model [{\it Math. Biosci.} {\bf 75}, 3-22 (1985)] which is widely used in computational epidemiology. Few analytical results are however available and in particular little is known about paths followed by epidemics and disease arrival times. We study the arrival time of a disease in a city as a function of the starting seed of the epidemics. We propose an analytical Ansatz, test it in the case of a spreading on the world wide air transportation network, and show that it predicts accurately the arrival order of a disease in world-wide cities.
1604.07649
Guillaume Attuel
G. Attuel and N. Derval and T. Desplantez and M. Haissaguerre and M. Hocini and P. Ja\"is and R. Dubois
Critical fluctuations of the electrical activity of the heart: Shortcomings of models of excitability and interpretation
submitted to EPL: received 12 August 2013, rejected 27 september 2013
null
null
null
q-bio.TO
http://creativecommons.org/licenses/by-nc-sa/4.0/
We report unexpected evidence of critical fluctuations of the electric potential of the heart during atrial fibrillation in humans. Scale invariance and long range correlations are found, which we show cannot be accounted for solely with the property of excitability, since disorder emerges by the formation of chaotic patterns in excitable media. To shed light on the data, we discuss the hypothesis that, in fact, fibrillation appears through a phase transition, which we compare on phenomenological grounds to a quenched-in disorder magnetic transition. We infer that, during propagation of pulses, random pinning might occur due to random modulation of the gap junction channels.
[ { "created": "Fri, 22 Apr 2016 16:12:06 GMT", "version": "v1" } ]
2016-04-27
[ [ "Attuel", "G.", "" ], [ "Derval", "N.", "" ], [ "Desplantez", "T.", "" ], [ "Haissaguerre", "M.", "" ], [ "Hocini", "M.", "" ], [ "Jaïs", "P.", "" ], [ "Dubois", "R.", "" ] ]
We report unexpected evidence of critical fluctuations of the electric potential of the heart during atrial fibrillation in humans. Scale invariance and long range correlations are found, which we show cannot be accounted for solely with the property of excitability, since disorder emerges by the formation of chaotic patterns in excitable media. To shed light on the data, we discuss the hypothesis that, in fact, fibrillation appears through a phase transition, which we compare on phenomenological grounds to a quenched-in disorder magnetic transition. We infer that, during propagation of pulses, random pinning might occur due to random modulation of the gap junction channels.
2007.04765
Omar El Housni
Omar El Housni, Mika Sumida, Paat Rusmevichientong, Huseyin Topaloglu, Serhan Ziya
Future Evolution of COVID-19 Pandemic in North Carolina: Can We Flatten the Curve?
arXiv admin note: substantial text overlap with arXiv:2005.14700
null
null
null
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
On June 24th, Governor Cooper announced that North Carolina will not be moving into Phase 3 of its reopening process at least until July 17th. Given the recent increases in daily positive cases and hospitalizations, this decision was not surprising. However, given the political and economic pressures which are forcing the state to reopen, it is not clear what actions will help North Carolina to avoid the worst. We use a compartmentalized model to study the effects of social distancing measures and testing capacity combined with contact tracing on the evolution of the pandemic in North Carolina until the end of the year. We find that going back to restrictions that were in place during Phase 1 will slow down the spread but if the state wants to continue to reopen or at least remain in Phase 2 or Phase 3 it needs to significantly expand its testing and contact tracing capacity. Even under our best-case scenario of high contact tracing effectiveness, the number of contact tracers the state currently employs is inadequate.
[ { "created": "Fri, 3 Jul 2020 15:53:34 GMT", "version": "v1" } ]
2020-07-10
[ [ "Housni", "Omar El", "" ], [ "Sumida", "Mika", "" ], [ "Rusmevichientong", "Paat", "" ], [ "Topaloglu", "Huseyin", "" ], [ "Ziya", "Serhan", "" ] ]
On June 24th, Governor Cooper announced that North Carolina will not be moving into Phase 3 of its reopening process at least until July 17th. Given the recent increases in daily positive cases and hospitalizations, this decision was not surprising. However, given the political and economic pressures which are forcing the state to reopen, it is not clear what actions will help North Carolina to avoid the worst. We use a compartmentalized model to study the effects of social distancing measures and testing capacity combined with contact tracing on the evolution of the pandemic in North Carolina until the end of the year. We find that going back to restrictions that were in place during Phase 1 will slow down the spread but if the state wants to continue to reopen or at least remain in Phase 2 or Phase 3 it needs to significantly expand its testing and contact tracing capacity. Even under our best-case scenario of high contact tracing effectiveness, the number of contact tracers the state currently employs is inadequate.
1311.0399
Sam Greenbury
Sam F. Greenbury, Iain G. Johnston, Ard A. Louis, Sebastian E. Ahnert
A tractable genotype-phenotype map for the self-assembly of protein quaternary structure
12 pages, 6 figures
null
null
null
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The mapping between biological genotypes and phenotypes is central to the study of biological evolution. Here we introduce a rich, intuitive, and biologically realistic genotype-phenotype (GP) map, that serves as a model of self-assembling biological structures, such as protein complexes, and remains computationally and analytically tractable. Our GP map arises naturally from the self-assembly of polyomino structures on a 2D lattice and exhibits a number of properties: $\textit{redundancy}$ (genotypes vastly outnumber phenotypes), $\textit{phenotype bias}$ (genotypic redundancy varies greatly between phenotypes), $\textit{genotype component disconnectivity}$ (phenotypes consist of disconnected mutational networks) and $\textit{shape space covering}$ (most phenotypes can be reached in a small number of mutations). We also show that the mutational robustness of phenotypes scales very roughly logarithmically with phenotype redundancy and is positively correlated with phenotypic evolvability. Although our GP map describes the assembly of disconnected objects, it shares many properties with other popular GP maps for connected units, such as models for RNA secondary structure or the HP lattice model for protein tertiary structure. The remarkable fact that these important properties similarly emerge from such different models suggests the possibility that universal features underlie a much wider class of biologically realistic GP maps.
[ { "created": "Sat, 2 Nov 2013 17:50:50 GMT", "version": "v1" } ]
2013-11-05
[ [ "Greenbury", "Sam F.", "" ], [ "Johnston", "Iain G.", "" ], [ "Louis", "Ard A.", "" ], [ "Ahnert", "Sebastian E.", "" ] ]
The mapping between biological genotypes and phenotypes is central to the study of biological evolution. Here we introduce a rich, intuitive, and biologically realistic genotype-phenotype (GP) map, that serves as a model of self-assembling biological structures, such as protein complexes, and remains computationally and analytically tractable. Our GP map arises naturally from the self-assembly of polyomino structures on a 2D lattice and exhibits a number of properties: $\textit{redundancy}$ (genotypes vastly outnumber phenotypes), $\textit{phenotype bias}$ (genotypic redundancy varies greatly between phenotypes), $\textit{genotype component disconnectivity}$ (phenotypes consist of disconnected mutational networks) and $\textit{shape space covering}$ (most phenotypes can be reached in a small number of mutations). We also show that the mutational robustness of phenotypes scales very roughly logarithmically with phenotype redundancy and is positively correlated with phenotypic evolvability. Although our GP map describes the assembly of disconnected objects, it shares many properties with other popular GP maps for connected units, such as models for RNA secondary structure or the HP lattice model for protein tertiary structure. The remarkable fact that these important properties similarly emerge from such different models suggests the possibility that universal features underlie a much wider class of biologically realistic GP maps.
2005.08380
Andy Lau
Andy M. Lau, Jurgen Claesen, Kjetil Hansen, Argyris Politis
Deuteros 2.0: Peptide-level significance testing of data from hydrogen deuterium exchange mass spectrometry
Application note with 3 pages, 1 figure
null
null
null
q-bio.QM stat.AP
http://creativecommons.org/licenses/by-nc-sa/4.0/
Summary: Hydrogen deuterium exchange mass spectrometry (HDX-MS) is becoming increasing routine for monitoring changes in the structural dynamics of proteins. Differential HDX-MS allows comparison of individual protein states, such as in the absence or presence of a ligand. This can be used to attribute changes in conformation to binding events, allowing the mapping of entire con-formational networks. As such, the number of necessary cross-state comparisons quickly increas-es as additional states are introduced to the system of study. There are currently very few software packages available that offer quick and informative comparison of HDX-MS datasets and even few-er which offer statistical analysis and advanced visualization. Following the feedback from our origi-nal software Deuteros, we present Deuteros 2.0 which has been redesigned from the ground up to fulfil a greater role in the HDX-MS analysis pipeline. Deuteros 2.0 features a repertoire of facilities for back exchange correction, data summarization, peptide-level statistical analysis and advanced data plotting features. Availability: Deuteros 2.0 can be downloaded from https://github.com/andymlau/Deuteros_2.0 under the Apache 2.0 license. Installation of Deuteros 2.0 requires the MATLAB Runtime Library available free of charge from MathWorks (https://www.mathworks.com/products/compiler/matlab-runtime.html) and is available for both Windows and Mac operating systems.
[ { "created": "Sun, 17 May 2020 22:01:10 GMT", "version": "v1" } ]
2020-05-19
[ [ "Lau", "Andy M.", "" ], [ "Claesen", "Jurgen", "" ], [ "Hansen", "Kjetil", "" ], [ "Politis", "Argyris", "" ] ]
Summary: Hydrogen deuterium exchange mass spectrometry (HDX-MS) is becoming increasing routine for monitoring changes in the structural dynamics of proteins. Differential HDX-MS allows comparison of individual protein states, such as in the absence or presence of a ligand. This can be used to attribute changes in conformation to binding events, allowing the mapping of entire con-formational networks. As such, the number of necessary cross-state comparisons quickly increas-es as additional states are introduced to the system of study. There are currently very few software packages available that offer quick and informative comparison of HDX-MS datasets and even few-er which offer statistical analysis and advanced visualization. Following the feedback from our origi-nal software Deuteros, we present Deuteros 2.0 which has been redesigned from the ground up to fulfil a greater role in the HDX-MS analysis pipeline. Deuteros 2.0 features a repertoire of facilities for back exchange correction, data summarization, peptide-level statistical analysis and advanced data plotting features. Availability: Deuteros 2.0 can be downloaded from https://github.com/andymlau/Deuteros_2.0 under the Apache 2.0 license. Installation of Deuteros 2.0 requires the MATLAB Runtime Library available free of charge from MathWorks (https://www.mathworks.com/products/compiler/matlab-runtime.html) and is available for both Windows and Mac operating systems.
1705.03322
Ivo Siekmann
Ivo Siekmann
An applied mathematician's perspective on Rosennean Complexity
33 pages, 1 figure
null
null
null
q-bio.OT
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The theoretical biologist Robert Rosen developed a highly original approach for investigating the question "What is life?", the most fundamental problem of biology. Considering that Rosen made extensive use of mathematics it might seem surprising that his ideas have only rarely been implemented in mathematical models. On the one hand, Rosen propagates relational models that neglect underlying structural details of the components and focus on relationships between the elements of a biological system, according to the motto "throw away the physics, keep the organisation". Rosen's strong rejection of mechanistic models that he implicitly associates with a strong form of reductionism might have deterred mathematical modellers from adopting his ideas for their own work. On the other hand Rosen's presentation of his modelling framework, (M,R) systems, is highly abstract which makes it hard to appreciate how this approach could be applied to concrete biological problems. In this article, both the mathematics as well as those aspects of Rosen's work are analysed that relate to his philosophical ideas. It is shown that Rosen's relational models are a particular type of mechanistic model with specific underlying assumptions rather than a different kind of model that excludes mechanistic models. The strengths and weaknesses of relational models are investigated by comparison with current network biology literature. Finally, it is argued that Rosen's definition of life, "organisms are closed to efficient causation", should be considered as a hypothesis to be tested and ideas how this postulate could be implemented in mathematical models are presented.
[ { "created": "Thu, 4 May 2017 16:50:37 GMT", "version": "v1" }, { "created": "Mon, 14 Aug 2017 10:22:12 GMT", "version": "v2" } ]
2017-08-15
[ [ "Siekmann", "Ivo", "" ] ]
The theoretical biologist Robert Rosen developed a highly original approach for investigating the question "What is life?", the most fundamental problem of biology. Considering that Rosen made extensive use of mathematics it might seem surprising that his ideas have only rarely been implemented in mathematical models. On the one hand, Rosen propagates relational models that neglect underlying structural details of the components and focus on relationships between the elements of a biological system, according to the motto "throw away the physics, keep the organisation". Rosen's strong rejection of mechanistic models that he implicitly associates with a strong form of reductionism might have deterred mathematical modellers from adopting his ideas for their own work. On the other hand Rosen's presentation of his modelling framework, (M,R) systems, is highly abstract which makes it hard to appreciate how this approach could be applied to concrete biological problems. In this article, both the mathematics as well as those aspects of Rosen's work are analysed that relate to his philosophical ideas. It is shown that Rosen's relational models are a particular type of mechanistic model with specific underlying assumptions rather than a different kind of model that excludes mechanistic models. The strengths and weaknesses of relational models are investigated by comparison with current network biology literature. Finally, it is argued that Rosen's definition of life, "organisms are closed to efficient causation", should be considered as a hypothesis to be tested and ideas how this postulate could be implemented in mathematical models are presented.
1404.3655
Henrike Heyne
Henrike O. Heyne, Susann Lautenschl\"ager, Ronald Nelson, Fran\c{c}ois Besnier, Maxime Rotival, Alexander Cagan, Rimma Kozhemyakina, Irina Z. Plyusnina, Lyudmila Trut, \"Orjan Carlborg, Enrico Petretto, Leonid Kruglyak, Svante P\"a\"abo, Torsten Sch\"oneberg, Frank W. Albert
Genetic Influences on Brain Gene Expression in Rats Selected for Tameness and Aggression
null
null
null
null
q-bio.GN
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Inter-individual differences in many behaviors are partly due to genetic differences, but the identification of the genes and variants that influence behavior remains challenging. Here, we studied an F2 intercross of two outbred lines of rats selected for tame and aggressive behavior towards humans for more than 64 generations. By using a mapping approach that is able to identify genetic loci segregating within the lines, we identified four times more loci influencing tameness and aggression than by an approach that assumes fixation of causative alleles, suggesting that many causative loci were not driven to fixation by the selection. We used RNA sequencing in 150 F2 animals to identify hundreds of loci that influence brain gene expression. Several of these loci colocalize with tameness loci and may reflect the same genetic variants. Through analyses of correlations between allele effects on behavior and gene expression, differential expression between the tame and aggressive rat selection lines, and correlations between gene expression and tameness in F2 animals, we identify the genes Gltscr2, Lgi4, Zfp40 and Slc17a7 as candidate contributors to the strikingly different behavior of the tame and aggressive animals.
[ { "created": "Mon, 14 Apr 2014 17:09:25 GMT", "version": "v1" } ]
2014-04-15
[ [ "Heyne", "Henrike O.", "" ], [ "Lautenschläger", "Susann", "" ], [ "Nelson", "Ronald", "" ], [ "Besnier", "François", "" ], [ "Rotival", "Maxime", "" ], [ "Cagan", "Alexander", "" ], [ "Kozhemyakina", "Rimma", "" ], [ "Plyusnina", "Irina Z.", "" ], [ "Trut", "Lyudmila", "" ], [ "Carlborg", "Örjan", "" ], [ "Petretto", "Enrico", "" ], [ "Kruglyak", "Leonid", "" ], [ "Pääbo", "Svante", "" ], [ "Schöneberg", "Torsten", "" ], [ "Albert", "Frank W.", "" ] ]
Inter-individual differences in many behaviors are partly due to genetic differences, but the identification of the genes and variants that influence behavior remains challenging. Here, we studied an F2 intercross of two outbred lines of rats selected for tame and aggressive behavior towards humans for more than 64 generations. By using a mapping approach that is able to identify genetic loci segregating within the lines, we identified four times more loci influencing tameness and aggression than by an approach that assumes fixation of causative alleles, suggesting that many causative loci were not driven to fixation by the selection. We used RNA sequencing in 150 F2 animals to identify hundreds of loci that influence brain gene expression. Several of these loci colocalize with tameness loci and may reflect the same genetic variants. Through analyses of correlations between allele effects on behavior and gene expression, differential expression between the tame and aggressive rat selection lines, and correlations between gene expression and tameness in F2 animals, we identify the genes Gltscr2, Lgi4, Zfp40 and Slc17a7 as candidate contributors to the strikingly different behavior of the tame and aggressive animals.
2105.03866
Guillaume Charrier
Lia Lamacque, Florian Sabin, Thierry Am\'eglio, St\'ephane Herbette, Guillaume Charrier
Detection of acoustic events in Lavender for measuring the xylem vulnerability to embolism and cellular damages
6 figures, 1 table, + 2 supplementary figures and 1 supplementary table
null
10.1093/jxb/erac061
null
q-bio.TO q-bio.QM
http://creativecommons.org/licenses/by-nc-sa/4.0/
Acoustic emission analysis is a promising technique to investigate the physiological events leading to drought-induced injuries and mortality. However, the nature and the source of the acoustic emissions are not fully understood and make the use of this technique difficult as a direct measure of the loss of xylem hydraulic conductance. In this study, acoustic emissions were recorded during severe dehydration in lavender plants and compared to the dynamics of embolism development and cell lysis. The timing and characteristics of acoustic signals from two independent recording systems were compared by principal component analysis. In parallel, changes in water potential, branch diameter, loss of hydraulic conductance and electrolyte leakage were measured to quantify drought-induced damages. Two distinct phases of acoustic emissions were observed during dehydration: the first one associated with a rapid loss of diameter and a significant increase in loss of xylem conductance (90%) and the second one with a significant increase in electrolyte leakage and slower diameter changes. This second phase corresponds to a complete loss of recovery capacity. The acoustic signals of both phases were discriminated by the third and fourth principal components. The loss of hydraulic conductance during the first acoustic phase suggests the hydraulic origin of these signals (i.e. cavitation events). For the second phase, the signals showed much higher variability between plants and acoustic systems suggesting that the sources of these signals may be plural, although likely including cellular damage. A simple algorithm was developed to discriminate hydraulic-related acoustic signals from other sources, allowing the reconstruction of dynamic hydraulic vulnerability curves. However, hydraulic failure precedes cellular damage and lack of whole plant recovery is associated to these latter.
[ { "created": "Sun, 9 May 2021 08:00:24 GMT", "version": "v1" } ]
2022-02-17
[ [ "Lamacque", "Lia", "" ], [ "Sabin", "Florian", "" ], [ "Améglio", "Thierry", "" ], [ "Herbette", "Stéphane", "" ], [ "Charrier", "Guillaume", "" ] ]
Acoustic emission analysis is a promising technique to investigate the physiological events leading to drought-induced injuries and mortality. However, the nature and the source of the acoustic emissions are not fully understood and make the use of this technique difficult as a direct measure of the loss of xylem hydraulic conductance. In this study, acoustic emissions were recorded during severe dehydration in lavender plants and compared to the dynamics of embolism development and cell lysis. The timing and characteristics of acoustic signals from two independent recording systems were compared by principal component analysis. In parallel, changes in water potential, branch diameter, loss of hydraulic conductance and electrolyte leakage were measured to quantify drought-induced damages. Two distinct phases of acoustic emissions were observed during dehydration: the first one associated with a rapid loss of diameter and a significant increase in loss of xylem conductance (90%) and the second one with a significant increase in electrolyte leakage and slower diameter changes. This second phase corresponds to a complete loss of recovery capacity. The acoustic signals of both phases were discriminated by the third and fourth principal components. The loss of hydraulic conductance during the first acoustic phase suggests the hydraulic origin of these signals (i.e. cavitation events). For the second phase, the signals showed much higher variability between plants and acoustic systems suggesting that the sources of these signals may be plural, although likely including cellular damage. A simple algorithm was developed to discriminate hydraulic-related acoustic signals from other sources, allowing the reconstruction of dynamic hydraulic vulnerability curves. However, hydraulic failure precedes cellular damage and lack of whole plant recovery is associated to these latter.
1211.7196
Daniel Gamermann Dr.
D. Gamermann, A. Montagud, R. A. Jaime Infante, J. Triana, P. F. de C\'ordoba, J. F. Urchuegu\'ia
PyNetMet: Python tools for efficient work with networks and metabolic models
1 Figure, 2 Tables
null
null
null
q-bio.MN
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Background: The study of genome-scale metabolic models and their underlying networks is one of the most important fields in systems biology. The complexity of these models and their description makes the use of computational tools an essential element in their research. Therefore there is a strong need of efficient and versatile computational tools for the research in this area. Results: In this manuscript we present PyNetMet, a Python library of tools to work with networks and metabolic models. These are open-source free tools for use in a Python platform, which adds considerably versatility to them when compared with their desktop software similars. On the other hand these tools allow one to work with different standards of metabolic models (OptGene and SBML) and the fact that they are programmed in Python opens the possibility of efficient integration with any other already existing Python tool. Conclusions: PyNetMet is, therefore, a collection of computational tools that will facilitate the research work with metabolic models and networks.
[ { "created": "Fri, 30 Nov 2012 09:25:06 GMT", "version": "v1" } ]
2012-12-03
[ [ "Gamermann", "D.", "" ], [ "Montagud", "A.", "" ], [ "Infante", "R. A. Jaime", "" ], [ "Triana", "J.", "" ], [ "de Córdoba", "P. F.", "" ], [ "Urchueguía", "J. F.", "" ] ]
Background: The study of genome-scale metabolic models and their underlying networks is one of the most important fields in systems biology. The complexity of these models and their description makes the use of computational tools an essential element in their research. Therefore there is a strong need of efficient and versatile computational tools for the research in this area. Results: In this manuscript we present PyNetMet, a Python library of tools to work with networks and metabolic models. These are open-source free tools for use in a Python platform, which adds considerably versatility to them when compared with their desktop software similars. On the other hand these tools allow one to work with different standards of metabolic models (OptGene and SBML) and the fact that they are programmed in Python opens the possibility of efficient integration with any other already existing Python tool. Conclusions: PyNetMet is, therefore, a collection of computational tools that will facilitate the research work with metabolic models and networks.
q-bio/0511027
Changbong Hyeon
G. Caliskan, C. Hyeon, U. Perez-Salas, R. M. Briber, S. A. Woodson, and D. Thirumalai
Persistence Length Changes Dramatically as RNA Folds
4 page. Phys. Rev. Lett. in press
Phys. Rev. Lett 95, 268303 (2005)
10.1103/PhysRevLett.95.268303
null
q-bio.BM cond-mat.soft q-bio.QM
null
We determine the persistence length, $l_p$, for a bacterial group I ribozyme as a function of concentration of monovalent and divalent cations by fitting the distance distribution functions $P(r)$ obtained from small angle X-ray scattering intensity data to the asymptotic form of the calculated $P_{WLC}(r)$ for a worm-like chain (WLC). The $l_p$ values change dramatically over a narrow range of \Mg concentration from $\sim$21 \AA in the unfolded state (\textbf{U}) to $\sim$10 \AA in the compact ($\mathrm{I_C}$) and native states. Variations in $l_p$ with increasing \Na concentration are more gradual. In accord with the predictions of polyelectrolyte theory we find $l_p \propto 1/ \kappa^2$ where $\kappa$ is the inverse Debye-screening length.
[ { "created": "Wed, 16 Nov 2005 00:01:08 GMT", "version": "v1" } ]
2009-11-11
[ [ "Caliskan", "G.", "" ], [ "Hyeon", "C.", "" ], [ "Perez-Salas", "U.", "" ], [ "Briber", "R. M.", "" ], [ "Woodson", "S. A.", "" ], [ "Thirumalai", "D.", "" ] ]
We determine the persistence length, $l_p$, for a bacterial group I ribozyme as a function of concentration of monovalent and divalent cations by fitting the distance distribution functions $P(r)$ obtained from small angle X-ray scattering intensity data to the asymptotic form of the calculated $P_{WLC}(r)$ for a worm-like chain (WLC). The $l_p$ values change dramatically over a narrow range of \Mg concentration from $\sim$21 \AA in the unfolded state (\textbf{U}) to $\sim$10 \AA in the compact ($\mathrm{I_C}$) and native states. Variations in $l_p$ with increasing \Na concentration are more gradual. In accord with the predictions of polyelectrolyte theory we find $l_p \propto 1/ \kappa^2$ where $\kappa$ is the inverse Debye-screening length.
2307.11365
Sarah Vollert
Sarah A. Vollert, Christopher Drovandi, Matthew P. Adams
Unlocking ensemble ecosystem modelling for large and complex networks
null
PLoS Comput Biol 20(3): e1011976
10.1371/journal.pcbi.1011976
null
q-bio.PE stat.AP
http://creativecommons.org/licenses/by-sa/4.0/
The potential effects of conservation actions on threatened species can be predicted using ensemble ecosystem models by forecasting populations with and without intervention. These model ensembles commonly assume stable coexistence of species in the absence of available data. However, existing ensemble-generation methods become computationally inefficient as the size of the ecosystem network increases, preventing larger networks from being studied. We present a novel sequential Monte Carlo sampling approach for ensemble generation that is orders of magnitude faster than existing approaches. We demonstrate that the methods produce equivalent parameter inferences, model predictions, and tightly constrained parameter combinations using a novel sensitivity analysis method. For one case study, we demonstrate a speed-up from 108 days to 6 hours, while maintaining equivalent ensembles. Additionally, we demonstrate how to identify the parameter combinations that strongly drive feasibility and stability, drawing ecological insight from the ensembles. Now, for the first time, larger and more realistic networks can be practically simulated and analysed.
[ { "created": "Fri, 21 Jul 2023 05:36:24 GMT", "version": "v1" }, { "created": "Thu, 25 Jan 2024 01:21:48 GMT", "version": "v2" } ]
2024-03-22
[ [ "Vollert", "Sarah A.", "" ], [ "Drovandi", "Christopher", "" ], [ "Adams", "Matthew P.", "" ] ]
The potential effects of conservation actions on threatened species can be predicted using ensemble ecosystem models by forecasting populations with and without intervention. These model ensembles commonly assume stable coexistence of species in the absence of available data. However, existing ensemble-generation methods become computationally inefficient as the size of the ecosystem network increases, preventing larger networks from being studied. We present a novel sequential Monte Carlo sampling approach for ensemble generation that is orders of magnitude faster than existing approaches. We demonstrate that the methods produce equivalent parameter inferences, model predictions, and tightly constrained parameter combinations using a novel sensitivity analysis method. For one case study, we demonstrate a speed-up from 108 days to 6 hours, while maintaining equivalent ensembles. Additionally, we demonstrate how to identify the parameter combinations that strongly drive feasibility and stability, drawing ecological insight from the ensembles. Now, for the first time, larger and more realistic networks can be practically simulated and analysed.
1304.7991
Simon Mitternacht
S. {\AE}. J\'onsson, S. Mitternacht, A. Irb\"ack
Mechanical resistance in unstructured proteins
v3: Added correct journal reference plus minor corrections
Biophysical Journal, Volume 104, Issue 12, 2725-2732, 18 June 2013
10.1016/j.bpj.2013.05.003
null
q-bio.BM physics.bio-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Single-molecule pulling experiments on unstructured proteins linked to neurodegenerative diseases have measured rupture forces comparable to those for stable folded proteins. To investigate the structural mechanisms of this unexpected force resistance, we perform pulling simulations of the amyloid {\beta}-peptide (A{\beta}) and {\alpha}-synuclein ({\alpha}S), starting from simulated conformational ensembles for the free monomers. For both proteins, the simulations yield a set of rupture events that agree well with the experimental data. By analyzing the conformations right before rupture in each event, we find that the mechanically resistant structures share a common architecture, with similarities to the folds adopted by A{\beta} and {\alpha}S in amyloid fibrils. The disease-linked Arctic mutation of A{\beta} is found to increase the occurrence of highly force-resistant structures. Our study suggests that the high rupture forces observed in A{\beta} and {\alpha}S pulling experiments are caused by structures that might have a key role in amyloid formation.
[ { "created": "Tue, 30 Apr 2013 13:30:54 GMT", "version": "v1" }, { "created": "Wed, 1 May 2013 09:14:35 GMT", "version": "v2" }, { "created": "Tue, 18 Jun 2013 19:13:38 GMT", "version": "v3" } ]
2013-06-19
[ [ "Jónsson", "S. Æ.", "" ], [ "Mitternacht", "S.", "" ], [ "Irbäck", "A.", "" ] ]
Single-molecule pulling experiments on unstructured proteins linked to neurodegenerative diseases have measured rupture forces comparable to those for stable folded proteins. To investigate the structural mechanisms of this unexpected force resistance, we perform pulling simulations of the amyloid {\beta}-peptide (A{\beta}) and {\alpha}-synuclein ({\alpha}S), starting from simulated conformational ensembles for the free monomers. For both proteins, the simulations yield a set of rupture events that agree well with the experimental data. By analyzing the conformations right before rupture in each event, we find that the mechanically resistant structures share a common architecture, with similarities to the folds adopted by A{\beta} and {\alpha}S in amyloid fibrils. The disease-linked Arctic mutation of A{\beta} is found to increase the occurrence of highly force-resistant structures. Our study suggests that the high rupture forces observed in A{\beta} and {\alpha}S pulling experiments are caused by structures that might have a key role in amyloid formation.
1811.07592
Giulio Bondanelli
Giulio Bondanelli and Srdjan Ostojic
Coding with transient trajectories in recurrent neural networks
null
null
null
null
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Following a stimulus, the neural response typically strongly varies in time and across neurons before settling to a steady-state. While classical population coding theory disregards the temporal dimension, recent works have argued that trajectories of transient activity can be particularly informative about stimulus identity and may form the basis of computations through dynamics. Yet the dynamical mechanisms needed to generate a population code based on transient trajectories have not been fully elucidated. Here we examine transient coding in a broad class of high-dimensional linear networks of recurrently connected units. We start by reviewing a well-known result that leads to a distinction between two classes of networks: networks in which all inputs lead to weak, decaying transients, and networks in which specific inputs elicit strongly amplified transient responses and are mapped onto orthogonal output states during the dynamics. Theses two classes are simply distinguished based on the spectrum of the symmetric part of the connectivity matrix. For the second class of networks, which is a sub-class of non-normal networks, we provide a procedure to identify transiently amplified inputs and the corresponding readouts. We first apply these results to standard randomly-connected and two-population networks. We then build minimal, low-rank networks that robustly implement trajectories mapping a specific input onto a specific output state. Finally, we demonstrate that the capacity of the obtained networks increases proportionally with their size.
[ { "created": "Mon, 19 Nov 2018 10:25:31 GMT", "version": "v1" }, { "created": "Thu, 4 Jul 2019 13:52:11 GMT", "version": "v2" } ]
2019-07-05
[ [ "Bondanelli", "Giulio", "" ], [ "Ostojic", "Srdjan", "" ] ]
Following a stimulus, the neural response typically strongly varies in time and across neurons before settling to a steady-state. While classical population coding theory disregards the temporal dimension, recent works have argued that trajectories of transient activity can be particularly informative about stimulus identity and may form the basis of computations through dynamics. Yet the dynamical mechanisms needed to generate a population code based on transient trajectories have not been fully elucidated. Here we examine transient coding in a broad class of high-dimensional linear networks of recurrently connected units. We start by reviewing a well-known result that leads to a distinction between two classes of networks: networks in which all inputs lead to weak, decaying transients, and networks in which specific inputs elicit strongly amplified transient responses and are mapped onto orthogonal output states during the dynamics. Theses two classes are simply distinguished based on the spectrum of the symmetric part of the connectivity matrix. For the second class of networks, which is a sub-class of non-normal networks, we provide a procedure to identify transiently amplified inputs and the corresponding readouts. We first apply these results to standard randomly-connected and two-population networks. We then build minimal, low-rank networks that robustly implement trajectories mapping a specific input onto a specific output state. Finally, we demonstrate that the capacity of the obtained networks increases proportionally with their size.
1309.4039
Gerrit Ansmann
Klaus Lehnertz and Gerrit Ansmann and Stephan Bialonski and Henning Dickten and Christian Geier and Stephan Porz
Evolving networks in the human epileptic brain
In press (Physica D)
Physica D 267, 7-15 (2014)
10.1016/j.physd.2013.06.009
null
q-bio.NC physics.data-an physics.med-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Network theory provides novel concepts that promise an improved characterization of interacting dynamical systems. Within this framework, evolving networks can be considered as being composed of nodes, representing systems, and of time-varying edges, representing interactions between these systems. This approach is highly attractive to further our understanding of the physiological and pathophysiological dynamics in human brain networks. Indeed, there is growing evidence that the epileptic process can be regarded as a large-scale network phenomenon. We here review methodologies for inferring networks from empirical time series and for a characterization of these evolving networks. We summarize recent findings derived from studies that investigate human epileptic brain networks evolving on timescales ranging from few seconds to weeks. We point to possible pitfalls and open issues, and discuss future perspectives.
[ { "created": "Mon, 16 Sep 2013 17:05:56 GMT", "version": "v1" } ]
2014-08-26
[ [ "Lehnertz", "Klaus", "" ], [ "Ansmann", "Gerrit", "" ], [ "Bialonski", "Stephan", "" ], [ "Dickten", "Henning", "" ], [ "Geier", "Christian", "" ], [ "Porz", "Stephan", "" ] ]
Network theory provides novel concepts that promise an improved characterization of interacting dynamical systems. Within this framework, evolving networks can be considered as being composed of nodes, representing systems, and of time-varying edges, representing interactions between these systems. This approach is highly attractive to further our understanding of the physiological and pathophysiological dynamics in human brain networks. Indeed, there is growing evidence that the epileptic process can be regarded as a large-scale network phenomenon. We here review methodologies for inferring networks from empirical time series and for a characterization of these evolving networks. We summarize recent findings derived from studies that investigate human epileptic brain networks evolving on timescales ranging from few seconds to weeks. We point to possible pitfalls and open issues, and discuss future perspectives.
1409.0605
Tiberiu Harko
Tiberiu Harko, M. K. Mak
Travelling wave solutions of the reaction-diffusion mathematical model of glioblastoma growth: An Abel equation based approach
29 pages, 4 figures, accepted for publication in Mathematical Biosciences and Engineering
Mathematical Biosciences and Engineering, vol. 12, pp. 41-69, 2015
null
null
q-bio.TO physics.bio-ph q-bio.QM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We consider quasi-stationary (travelling wave type) solutions to a nonlinear reaction-diffusion equation with arbitrary, autonomous coefficients, describing the evolution of glioblastomas, aggressive primary brain tumors that are characterized by extensive infiltration into the brain and are highly resistant to treatment. The second order nonlinear equation describing the glioblastoma growth through travelling waves can be reduced to a first order Abel type equation. By using the integrability conditions for the Abel equation several classes of exact travelling wave solutions of the general reaction-diffusion equation that describes glioblastoma growth are obtained, corresponding to different forms of the product of the diffusion and reaction functions. The solutions are obtained by using the Chiellini lemma and the Lemke transformation, respectively, and the corresponding equations represent generalizations of the classical Fisher--Kolmogorov equation. The biological implications of two classes of solutions are also investigated by using both numerical and semi-analytical methods for realistic values of the biological parameters.
[ { "created": "Tue, 2 Sep 2014 04:06:45 GMT", "version": "v1" } ]
2014-12-17
[ [ "Harko", "Tiberiu", "" ], [ "Mak", "M. K.", "" ] ]
We consider quasi-stationary (travelling wave type) solutions to a nonlinear reaction-diffusion equation with arbitrary, autonomous coefficients, describing the evolution of glioblastomas, aggressive primary brain tumors that are characterized by extensive infiltration into the brain and are highly resistant to treatment. The second order nonlinear equation describing the glioblastoma growth through travelling waves can be reduced to a first order Abel type equation. By using the integrability conditions for the Abel equation several classes of exact travelling wave solutions of the general reaction-diffusion equation that describes glioblastoma growth are obtained, corresponding to different forms of the product of the diffusion and reaction functions. The solutions are obtained by using the Chiellini lemma and the Lemke transformation, respectively, and the corresponding equations represent generalizations of the classical Fisher--Kolmogorov equation. The biological implications of two classes of solutions are also investigated by using both numerical and semi-analytical methods for realistic values of the biological parameters.
q-bio/0508019
Jayprokas Chakrabarti
Smarajit Das, Zhumur Ghosh, Jayprokas Chakrabarti, Bibekanand Mallick and Satyabrata Sahoo
Positioning Crenarchaeal tRNA-Introns
15 pages, 2 figures
null
null
null
q-bio.GN
null
We precisely position a noncanonical intron in the odd second copy of tRNAAsp(GTC) gene in the newly sequenced crenarchaea S.acidocaldarius. The uniform assortment of some features from normal aspartate tDNA and some from those corresponding to non-standard amino acids conduce us to conjecture it to be a novel tRNA gene, probably coding for a modified aspartate residue. Further we reposition intron in tRNAHis(GUG) gene in P.aerophilum.The BHB motif at the exon-intron boundaries are re-analyzed and found to support our conjectures.
[ { "created": "Tue, 16 Aug 2005 10:28:12 GMT", "version": "v1" } ]
2007-05-23
[ [ "Das", "Smarajit", "" ], [ "Ghosh", "Zhumur", "" ], [ "Chakrabarti", "Jayprokas", "" ], [ "Mallick", "Bibekanand", "" ], [ "Sahoo", "Satyabrata", "" ] ]
We precisely position a noncanonical intron in the odd second copy of tRNAAsp(GTC) gene in the newly sequenced crenarchaea S.acidocaldarius. The uniform assortment of some features from normal aspartate tDNA and some from those corresponding to non-standard amino acids conduce us to conjecture it to be a novel tRNA gene, probably coding for a modified aspartate residue. Further we reposition intron in tRNAHis(GUG) gene in P.aerophilum.The BHB motif at the exon-intron boundaries are re-analyzed and found to support our conjectures.
1307.5878
Joshua M. Deutsch
J. M. Deutsch and Ian P. Lewis
Motor function in interpolar microtubules during metaphase
13 pages, 7 figures
null
null
null
q-bio.CB q-bio.BM q-bio.SC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We analyze experimental observations of microtubules undergoing small fluctuations about a "balance point" when mixed in solution of two different kinesin motor proteins, KLP61F and Ncd. It has been proposed that the microtubule movement is due to stochastic variations in the densities of the two species of motor proteins. We test this hypothesis here by showing how it maps onto a one-dimensional random walk in a random environment. Our estimate of the amplitude of the fluctuations agrees with experimental observations. We point out that there is an initial transient in the position of the microtubule where it will typically move of order its own length. We compare the physics of this gliding assay to a recent theory of the role of antagonistic motors on restricting interpolar microtubule sliding of a cell's mitotic spindle during prometaphase. It is concluded that randomly positioned antagonistic motors can restrict relative movement of microtubules, however they do so imperfectly. A variation in motor concentrations is also analyzed and shown to lead to greater control of spindle length.
[ { "created": "Mon, 22 Jul 2013 20:37:23 GMT", "version": "v1" } ]
2013-07-24
[ [ "Deutsch", "J. M.", "" ], [ "Lewis", "Ian P.", "" ] ]
We analyze experimental observations of microtubules undergoing small fluctuations about a "balance point" when mixed in solution of two different kinesin motor proteins, KLP61F and Ncd. It has been proposed that the microtubule movement is due to stochastic variations in the densities of the two species of motor proteins. We test this hypothesis here by showing how it maps onto a one-dimensional random walk in a random environment. Our estimate of the amplitude of the fluctuations agrees with experimental observations. We point out that there is an initial transient in the position of the microtubule where it will typically move of order its own length. We compare the physics of this gliding assay to a recent theory of the role of antagonistic motors on restricting interpolar microtubule sliding of a cell's mitotic spindle during prometaphase. It is concluded that randomly positioned antagonistic motors can restrict relative movement of microtubules, however they do so imperfectly. A variation in motor concentrations is also analyzed and shown to lead to greater control of spindle length.
1703.09994
Irina Kareva
Irina Kareva
Angiogenesis regulators as a possible key to accelerated growth of secondary tumors following primary tumor resection
null
null
null
null
q-bio.TO
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Resection of primary tumors is often followed by accelerated growth of metastases. Here we propose that this effect may be due to the fact that resection of primary tumor results in a decrease in the total systemic amount of angiogenesis stimulators, such as VEGF and bFGF. This in turn causes decrease in the systemic level of angiogenesis inhibitors, such as PF-4 and TSP-1, which at least temporarily relieves inhibition of secondary tumors, allowing them to grow. This construct is predicated on the notion that systemic level of angiogenesis inhibitors is regulated by the systemic level of angiogenesis stimulators, as the host is trying to maintain the homeostatic balance of stimulators to inhibitors in the body. We evaluate this hypothesis using a conceptual mathematical model and show that indeed, this mechanism can explain accelerated growth of secondary tumors following resection of a primary tumor. We also show that there exists a tradeoff between time of surgery and time to onset of metastatic growth. We conclude with a discussion of possible therapeutic approaches that may counteract this effect and reduce metastatic recurrences after surgery.
[ { "created": "Wed, 29 Mar 2017 12:10:30 GMT", "version": "v1" } ]
2017-03-30
[ [ "Kareva", "Irina", "" ] ]
Resection of primary tumors is often followed by accelerated growth of metastases. Here we propose that this effect may be due to the fact that resection of primary tumor results in a decrease in the total systemic amount of angiogenesis stimulators, such as VEGF and bFGF. This in turn causes decrease in the systemic level of angiogenesis inhibitors, such as PF-4 and TSP-1, which at least temporarily relieves inhibition of secondary tumors, allowing them to grow. This construct is predicated on the notion that systemic level of angiogenesis inhibitors is regulated by the systemic level of angiogenesis stimulators, as the host is trying to maintain the homeostatic balance of stimulators to inhibitors in the body. We evaluate this hypothesis using a conceptual mathematical model and show that indeed, this mechanism can explain accelerated growth of secondary tumors following resection of a primary tumor. We also show that there exists a tradeoff between time of surgery and time to onset of metastatic growth. We conclude with a discussion of possible therapeutic approaches that may counteract this effect and reduce metastatic recurrences after surgery.
1409.2207
Liane Gabora
Paul Sowden, Andrew Pringle, and Liane Gabora
The Shifting Sands of Creative Thinking: Connections to Dual Process Theory
17 pages
Thinking & Reasoning, 21(1), 40-60 (2015)
10.1080/13546783.2014.885464
null
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Dual process models of cognition suggest there are two kinds of thought: rapid, automatic Type 1 processes, and effortful, controlled Type 2 processes. Models of creative thinking also distinguish between two sets of processes: those involved in the generation of ideas, and those involved with their refinement, evaluation and/or selection. Here we review dual process models in both these literatures and delineate the similarities and differences. Both generative and evaluative creative processing modes involve elements that have been attributed to each of the dual processes of cognition. We explore the notion that creative thinking may rest upon the nature of a shifting process between generative and evaluative modes of thought. We suggest that through a synthesis application of the evidence bases on dual process models of cognition and from neuroimaging, together with developing chronometric approaches to explore the shifting process, could assist the development of interventions to facilitate creativity.
[ { "created": "Mon, 8 Sep 2014 05:04:30 GMT", "version": "v1" }, { "created": "Mon, 15 Jul 2019 21:51:13 GMT", "version": "v2" } ]
2019-07-17
[ [ "Sowden", "Paul", "" ], [ "Pringle", "Andrew", "" ], [ "Gabora", "Liane", "" ] ]
Dual process models of cognition suggest there are two kinds of thought: rapid, automatic Type 1 processes, and effortful, controlled Type 2 processes. Models of creative thinking also distinguish between two sets of processes: those involved in the generation of ideas, and those involved with their refinement, evaluation and/or selection. Here we review dual process models in both these literatures and delineate the similarities and differences. Both generative and evaluative creative processing modes involve elements that have been attributed to each of the dual processes of cognition. We explore the notion that creative thinking may rest upon the nature of a shifting process between generative and evaluative modes of thought. We suggest that through a synthesis application of the evidence bases on dual process models of cognition and from neuroimaging, together with developing chronometric approaches to explore the shifting process, could assist the development of interventions to facilitate creativity.
1307.7810
Aaron Darling
Denisa Duma, Mary Wootters, Anna C. Gilbert, Hung Q. Ngo, Atri Rudra, Matthew Alpert, Timothy J. Close, Gianfranco Ciardo, and Stefano Lonardi
Accurate Decoding of Pooled Sequenced Data Using Compressed Sensing
Peer-reviewed and presented as part of the 13th Workshop on Algorithms in Bioinformatics (WABI2013)
null
null
null
q-bio.QM cs.CE cs.IT math.IT q-bio.GN
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
In order to overcome the limitations imposed by DNA barcoding when multiplexing a large number of samples in the current generation of high-throughput sequencing instruments, we have recently proposed a new protocol that leverages advances in combinatorial pooling design (group testing) doi:10.1371/journal.pcbi.1003010. We have also demonstrated how this new protocol would enable de novo selective sequencing and assembly of large, highly-repetitive genomes. Here we address the problem of decoding pooled sequenced data obtained from such a protocol. Our algorithm employs a synergistic combination of ideas from compressed sensing and the decoding of error-correcting codes. Experimental results on synthetic data for the rice genome and real data for the barley genome show that our novel decoding algorithm enables significantly higher quality assemblies than the previous approach.
[ { "created": "Tue, 30 Jul 2013 04:34:34 GMT", "version": "v1" } ]
2013-08-02
[ [ "Duma", "Denisa", "" ], [ "Wootters", "Mary", "" ], [ "Gilbert", "Anna C.", "" ], [ "Ngo", "Hung Q.", "" ], [ "Rudra", "Atri", "" ], [ "Alpert", "Matthew", "" ], [ "Close", "Timothy J.", "" ], [ "Ciardo", "Gianfranco", "" ], [ "Lonardi", "Stefano", "" ] ]
In order to overcome the limitations imposed by DNA barcoding when multiplexing a large number of samples in the current generation of high-throughput sequencing instruments, we have recently proposed a new protocol that leverages advances in combinatorial pooling design (group testing) doi:10.1371/journal.pcbi.1003010. We have also demonstrated how this new protocol would enable de novo selective sequencing and assembly of large, highly-repetitive genomes. Here we address the problem of decoding pooled sequenced data obtained from such a protocol. Our algorithm employs a synergistic combination of ideas from compressed sensing and the decoding of error-correcting codes. Experimental results on synthetic data for the rice genome and real data for the barley genome show that our novel decoding algorithm enables significantly higher quality assemblies than the previous approach.
1605.02166
Tatsuya Sasaki
Tatsuya Sasaki, Isamu Okada, Yutaka Nakai
The evolution of conditional moral assessment in indirect reciprocity
27 pages, 2 figures and 2 tables
Scientific Reports 7, 41870 (2017)
10.1038/srep41870
null
q-bio.PE cs.SI nlin.AO physics.soc-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Indirect reciprocity is a major mechanism in the maintenance of cooperation among unrelated individuals. Indirect reciprocity leads to conditional cooperation according to social norms that discriminate the good (those who deserve to be rewarded with help) and the bad (those who should be punished by refusal of help). Despite intensive research, however, there is no definitive consensus on what social norms best promote cooperation through indirect reciprocity, and it remains unclear even how those who refuse to help the bad should be assessed. Here, we propose a new simple norm called "Staying" that prescribes abstaining from assessment. Under the Staying norm, the image of the person who makes the decision to give help stays the same as in the last assessment if the person on the receiving end has a bad image. In this case, the choice about whether or not to give help to the potential receiver does not affect the image of the potential giver. We analyze the Staying norm in terms of evolutionary game theory and demonstrate that Staying is most effective in establishing cooperation compared to the prevailing social norms, which rely on constant monitoring and unconditional assessment. The application of Staying suggests that the strict application of moral judgment is limited.
[ { "created": "Sat, 7 May 2016 10:28:53 GMT", "version": "v1" }, { "created": "Sat, 4 Feb 2017 13:39:06 GMT", "version": "v2" } ]
2017-02-07
[ [ "Sasaki", "Tatsuya", "" ], [ "Okada", "Isamu", "" ], [ "Nakai", "Yutaka", "" ] ]
Indirect reciprocity is a major mechanism in the maintenance of cooperation among unrelated individuals. Indirect reciprocity leads to conditional cooperation according to social norms that discriminate the good (those who deserve to be rewarded with help) and the bad (those who should be punished by refusal of help). Despite intensive research, however, there is no definitive consensus on what social norms best promote cooperation through indirect reciprocity, and it remains unclear even how those who refuse to help the bad should be assessed. Here, we propose a new simple norm called "Staying" that prescribes abstaining from assessment. Under the Staying norm, the image of the person who makes the decision to give help stays the same as in the last assessment if the person on the receiving end has a bad image. In this case, the choice about whether or not to give help to the potential receiver does not affect the image of the potential giver. We analyze the Staying norm in terms of evolutionary game theory and demonstrate that Staying is most effective in establishing cooperation compared to the prevailing social norms, which rely on constant monitoring and unconditional assessment. The application of Staying suggests that the strict application of moral judgment is limited.
1902.09482
Arni S.R. Srinivasa Rao
Arni S.R. Srinivasa Rao and Roy M. Anderson
Helminth Dynamics: Mean Number of Worms, Reproductive Rates
13 pages
Handbook of Statist., 36, Elsevier/North-Holland, Amsterdam, 2017
10.1016/bs.host.2017.05.003
null
q-bio.OT
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We derive formulas to compute mean number of worms in a newly Helminth infected population before secondary infections are started (population is closed). We have proved the two types of growth functions arise in this process as measurable functions.
[ { "created": "Mon, 25 Feb 2019 17:59:13 GMT", "version": "v1" } ]
2021-06-24
[ [ "Rao", "Arni S. R. Srinivasa", "" ], [ "Anderson", "Roy M.", "" ] ]
We derive formulas to compute mean number of worms in a newly Helminth infected population before secondary infections are started (population is closed). We have proved the two types of growth functions arise in this process as measurable functions.
1411.2205
Liaofu Luo
Liaofu Luo
A Model on Genome Evolution
13 pages
null
null
null
q-bio.OT
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
A model of genome evolution is proposed. Based on three assumptions the evolutionary theory of a genome is formulated. The general law on the direction of genome evolution is given. Both the deterministic classical equation and the stochastic quantum equation are proposed. It is proved that the classical equation can be put in a form of the least action principle and the latter can be used for obtaining the quantum generalization of the evolutionary law. The wave equation and uncertainty relation for the quantum evolution are deduced logically. It is shown that the classical trajectory is a limiting case of the general quantum evolution depicted in the coarse-grained time. The observed smooth/sudden evolution is interpreted by the alternating occurrence of the classical and quantum phases. The speciation event is explained by the quantum transition in quantum phase. Fundamental constants of time dimension, the quantization constant and the evolutionary inertia, are introduced for characterizing the genome evolution. The size of minimum genome is deduced from the quantum uncertainty lower bound. The present work shows the quantum law may be more general than thought, since it plays key roles not only in atomic physics, but also in genome evolution.
[ { "created": "Sun, 9 Nov 2014 07:20:08 GMT", "version": "v1" } ]
2014-11-11
[ [ "Luo", "Liaofu", "" ] ]
A model of genome evolution is proposed. Based on three assumptions the evolutionary theory of a genome is formulated. The general law on the direction of genome evolution is given. Both the deterministic classical equation and the stochastic quantum equation are proposed. It is proved that the classical equation can be put in a form of the least action principle and the latter can be used for obtaining the quantum generalization of the evolutionary law. The wave equation and uncertainty relation for the quantum evolution are deduced logically. It is shown that the classical trajectory is a limiting case of the general quantum evolution depicted in the coarse-grained time. The observed smooth/sudden evolution is interpreted by the alternating occurrence of the classical and quantum phases. The speciation event is explained by the quantum transition in quantum phase. Fundamental constants of time dimension, the quantization constant and the evolutionary inertia, are introduced for characterizing the genome evolution. The size of minimum genome is deduced from the quantum uncertainty lower bound. The present work shows the quantum law may be more general than thought, since it plays key roles not only in atomic physics, but also in genome evolution.
2302.11681
Hai-Jun Zhou
Zhen-Ye Huang, Ruyi Zhou, Miao Huang, Hai-Jun Zhou
Energy--Information Trade-off Induces Continuous and Discontinuous Phase Transitions in Lateral Predictive Coding
6 pages main text, supplementary text combined. This is an extensively revised version, containing new analytical results and numerical results
Science China Physics, Mechanics Astronomy 67, 260511 (2024)
10.1007/s11433-024-2341-2
null
q-bio.NC cond-mat.dis-nn
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Lateral predictive coding is a recurrent neural network which creates energy-efficient internal representations by exploiting statistical regularity in sensory inputs. Here we investigate the trade-off between information robustness and energy in a linear model of lateral predictive coding analytically and by numerical minimization of a free energy. We observe several phase transitions in the synaptic weight matrix, especially a continuous transition which breaks reciprocity and permutation symmetry and builds cyclic dominance and a discontinuous transition with the associated sudden emergence of tight balance between excitatory and inhibitory interactions. The optimal network follows an ideal-gas law in an extended temperature range and saturates the efficiency upper-bound of energy utilization. These results bring theoretical insights on the emergence and evolution of complex internal models in predictive processing systems.
[ { "created": "Wed, 22 Feb 2023 22:34:23 GMT", "version": "v1" }, { "created": "Thu, 11 Jan 2024 02:19:51 GMT", "version": "v2" } ]
2024-06-17
[ [ "Huang", "Zhen-Ye", "" ], [ "Zhou", "Ruyi", "" ], [ "Huang", "Miao", "" ], [ "Zhou", "Hai-Jun", "" ] ]
Lateral predictive coding is a recurrent neural network which creates energy-efficient internal representations by exploiting statistical regularity in sensory inputs. Here we investigate the trade-off between information robustness and energy in a linear model of lateral predictive coding analytically and by numerical minimization of a free energy. We observe several phase transitions in the synaptic weight matrix, especially a continuous transition which breaks reciprocity and permutation symmetry and builds cyclic dominance and a discontinuous transition with the associated sudden emergence of tight balance between excitatory and inhibitory interactions. The optimal network follows an ideal-gas law in an extended temperature range and saturates the efficiency upper-bound of energy utilization. These results bring theoretical insights on the emergence and evolution of complex internal models in predictive processing systems.
0907.0073
Anirban Banerji
Anirban Banerji, Indira Ghosh
Criteria to observe mesoscopic emergence of protein biophysical properties
A mathematical model, 25 pages
null
null
null
q-bio.BM q-bio.QM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Proteins are regularly described with some general indices (mass fractal dimension, surface fractal dimension, entropy, enthalpy, free energies, hydrophobicity, denaturation temperature etc..), which are inherently statistical in nature. These general indices emerge from innumerable (innately context-dependent and time-dependent) interactions between various atoms of a protein. Many a studies have been performed on the nature of these inter-atomic interactions and the change of profile of atomic fluctuations that they cause. However, we still do not know, under a given context, for a given duration of time, how does a macroscopic biophysical property emerge from the cumulative inter-atomic interactions. An exact answer to that question will involve bridging the gap between nano-scale distinguishable atomic description and macroscopic indistinguishable (statistical) measures, along the mesoscopic scale of observation. In this work we propose a computationally implementable mathematical model that derives expressions for observability of emergence of a macroscopic biophysical property from a set of interacting (fluctuating) atoms. Since most of the aforementioned interactions are non-linear in nature; observability criteria are derived for both linear and the non-linear descriptions of protein interior. The study assumes paramount importance in 21st-century biology, from both the theoretical and practical utilitarian point of view.
[ { "created": "Wed, 1 Jul 2009 06:49:45 GMT", "version": "v1" } ]
2009-07-02
[ [ "Banerji", "Anirban", "" ], [ "Ghosh", "Indira", "" ] ]
Proteins are regularly described with some general indices (mass fractal dimension, surface fractal dimension, entropy, enthalpy, free energies, hydrophobicity, denaturation temperature etc..), which are inherently statistical in nature. These general indices emerge from innumerable (innately context-dependent and time-dependent) interactions between various atoms of a protein. Many a studies have been performed on the nature of these inter-atomic interactions and the change of profile of atomic fluctuations that they cause. However, we still do not know, under a given context, for a given duration of time, how does a macroscopic biophysical property emerge from the cumulative inter-atomic interactions. An exact answer to that question will involve bridging the gap between nano-scale distinguishable atomic description and macroscopic indistinguishable (statistical) measures, along the mesoscopic scale of observation. In this work we propose a computationally implementable mathematical model that derives expressions for observability of emergence of a macroscopic biophysical property from a set of interacting (fluctuating) atoms. Since most of the aforementioned interactions are non-linear in nature; observability criteria are derived for both linear and the non-linear descriptions of protein interior. The study assumes paramount importance in 21st-century biology, from both the theoretical and practical utilitarian point of view.
2012.04227
Masayo Inoue
Masayo Inoue, Kunihiko Kaneko
Entangled gene regulatory networks with cooperative expression endow robust adaptive responses to unforeseen environmental changes
10 pages, 7 figures
Phys. Rev. Research 3, 033183 (2021)
10.1103/PhysRevResearch.3.033183
null
q-bio.MN physics.bio-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Living organisms must respond to environmental changes. Generally, accurate and rapid responses are provided by simple, unidirectional networks that connect inputs with outputs. Besides accuracy and speed, biological responses should also be robust to environmental or intracellular noise and mutations. Furthermore, cells must also respond to unforeseen environmental changes that have not previously been experienced, to avoid extinction prior to the evolutionary rewiring of their networks, which takes numerous generations. We have investigated gene regulatory networks that mutually activate or inhibit, and have demonstrated that complex entangled networks can make appropriate input-output relationships that satisfy the robust and adaptive responses required for unforeseen challenges. Such entangled networks function for sloppy and unreliable responses with low Hill coefficient reactions for the expression of each gene. To compensate for such sloppiness, several detours in the regulatory network exist. By taking advantage of the averaging over such detours, the network shows a higher robustness to environmental and intracellular noise as well as to mutations in the network, when compared to simple unidirectional circuits. Furthermore, the appropriate response to unforeseen challenges, allowing for functional outputs, is achieved as many genes exhibit similar dynamic expression responses, irrespective of inputs, as confirmed by applying dynamic time warping and dynamic mode decomposition. As complex entangled networks are common in gene regulatory networks and global gene expression responses are observed in microbial experiments, the present results provide a novel design principle for cellular networks.
[ { "created": "Tue, 8 Dec 2020 05:34:42 GMT", "version": "v1" } ]
2021-09-01
[ [ "Inoue", "Masayo", "" ], [ "Kaneko", "Kunihiko", "" ] ]
Living organisms must respond to environmental changes. Generally, accurate and rapid responses are provided by simple, unidirectional networks that connect inputs with outputs. Besides accuracy and speed, biological responses should also be robust to environmental or intracellular noise and mutations. Furthermore, cells must also respond to unforeseen environmental changes that have not previously been experienced, to avoid extinction prior to the evolutionary rewiring of their networks, which takes numerous generations. We have investigated gene regulatory networks that mutually activate or inhibit, and have demonstrated that complex entangled networks can make appropriate input-output relationships that satisfy the robust and adaptive responses required for unforeseen challenges. Such entangled networks function for sloppy and unreliable responses with low Hill coefficient reactions for the expression of each gene. To compensate for such sloppiness, several detours in the regulatory network exist. By taking advantage of the averaging over such detours, the network shows a higher robustness to environmental and intracellular noise as well as to mutations in the network, when compared to simple unidirectional circuits. Furthermore, the appropriate response to unforeseen challenges, allowing for functional outputs, is achieved as many genes exhibit similar dynamic expression responses, irrespective of inputs, as confirmed by applying dynamic time warping and dynamic mode decomposition. As complex entangled networks are common in gene regulatory networks and global gene expression responses are observed in microbial experiments, the present results provide a novel design principle for cellular networks.
2401.06166
Yan Ding
Yan Ding, Hao Cheng, Ziliang Ye, Ruyi Feng, Wei Tian, Peng Xie, Juan Zhang, Zhongze Gu
AdaMR: Adaptable Molecular Representation for Unified Pre-training Strategy
null
null
null
null
q-bio.BM cs.AI cs.LG
http://creativecommons.org/licenses/by-sa/4.0/
We propose Adjustable Molecular Representation (AdaMR), a new large-scale uniform pre-training strategy for small-molecule drugs, as a novel unified pre-training strategy. AdaMR utilizes a granularity-adjustable molecular encoding strategy, which is accomplished through a pre-training job termed molecular canonicalization, setting it apart from recent large-scale molecular models. This adaptability in granularity enriches the model's learning capability at multiple levels and improves its performance in multi-task scenarios. Specifically, the substructure-level molecular representation preserves information about specific atom groups or arrangements, influencing chemical properties and functionalities. This proves advantageous for tasks such as property prediction. Simultaneously, the atomic-level representation, combined with generative molecular canonicalization pre-training tasks, enhances validity, novelty, and uniqueness in generative tasks. All of these features work together to give AdaMR outstanding performance on a range of downstream tasks. We fine-tuned our proposed pre-trained model on six molecular property prediction tasks (MoleculeNet datasets) and two generative tasks (ZINC250K datasets), achieving state-of-the-art (SOTA) results on five out of eight tasks.
[ { "created": "Thu, 28 Dec 2023 10:53:17 GMT", "version": "v1" }, { "created": "Sat, 27 Apr 2024 13:28:02 GMT", "version": "v2" } ]
2024-04-30
[ [ "Ding", "Yan", "" ], [ "Cheng", "Hao", "" ], [ "Ye", "Ziliang", "" ], [ "Feng", "Ruyi", "" ], [ "Tian", "Wei", "" ], [ "Xie", "Peng", "" ], [ "Zhang", "Juan", "" ], [ "Gu", "Zhongze", "" ] ]
We propose Adjustable Molecular Representation (AdaMR), a new large-scale uniform pre-training strategy for small-molecule drugs, as a novel unified pre-training strategy. AdaMR utilizes a granularity-adjustable molecular encoding strategy, which is accomplished through a pre-training job termed molecular canonicalization, setting it apart from recent large-scale molecular models. This adaptability in granularity enriches the model's learning capability at multiple levels and improves its performance in multi-task scenarios. Specifically, the substructure-level molecular representation preserves information about specific atom groups or arrangements, influencing chemical properties and functionalities. This proves advantageous for tasks such as property prediction. Simultaneously, the atomic-level representation, combined with generative molecular canonicalization pre-training tasks, enhances validity, novelty, and uniqueness in generative tasks. All of these features work together to give AdaMR outstanding performance on a range of downstream tasks. We fine-tuned our proposed pre-trained model on six molecular property prediction tasks (MoleculeNet datasets) and two generative tasks (ZINC250K datasets), achieving state-of-the-art (SOTA) results on five out of eight tasks.
1911.08583
Jahan Schad
Jahan N. Schad
Mirror Neuron; A Beautiful Unnecessary Concept
null
null
null
Journal of Neurology & Stroke 2021; 11(6); 169-170
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The mirror neuron theory that has enjoyed continued validations was developed with no particular attention to the phenomenon of the vision. Understandably the perception of vision has always been thought to happen, naturally, as that for any of the other four senses. However, the reality that underlies this presumption is by no means obvious; vision perception is based on remote sensing of the ecology, fundamentally different form that of the other senses, which have tactile stimulation origin (contact with matter). While its reality, as explicated here, explains why the above presumption is true, it also bears heavily on the mirror neuron theory: the revelation of the nature of vision makes mirror neurons unnecessary. The extensive cognitive neurosciences investigation of primates and humans, over the past three decades, have experimentally validated the theory of mirror neurons which had been put forward early in the period (1980s and 1990s) based on the results of cognitive research experiments on the macaque monkeys. Based on further experimental works, phenomena such as learning, empathy, and some aspects of survival, are ascribed to the operations of this class of additional neurons. Here I reason that all the results of the efforts of the proponents of the theory can, not only find explanation in the context of the new theory of vision but also provide support for it. This new take of the phenomenon of vision is developed based on the nature of the experimental methods that have succeeded in developing some measure of vision for the blinds, and the inferences from the very likely nature of the computational strategy of the brain. I present evidence that the mental phenomena, which rendered the claim of the mirror neurons, are in essence the results of subjects beings variably touched by their ecology, through the coherent tactile operation of all senses.
[ { "created": "Thu, 14 Nov 2019 18:48:44 GMT", "version": "v1" } ]
2022-03-01
[ [ "Schad", "Jahan N.", "" ] ]
The mirror neuron theory that has enjoyed continued validations was developed with no particular attention to the phenomenon of the vision. Understandably the perception of vision has always been thought to happen, naturally, as that for any of the other four senses. However, the reality that underlies this presumption is by no means obvious; vision perception is based on remote sensing of the ecology, fundamentally different form that of the other senses, which have tactile stimulation origin (contact with matter). While its reality, as explicated here, explains why the above presumption is true, it also bears heavily on the mirror neuron theory: the revelation of the nature of vision makes mirror neurons unnecessary. The extensive cognitive neurosciences investigation of primates and humans, over the past three decades, have experimentally validated the theory of mirror neurons which had been put forward early in the period (1980s and 1990s) based on the results of cognitive research experiments on the macaque monkeys. Based on further experimental works, phenomena such as learning, empathy, and some aspects of survival, are ascribed to the operations of this class of additional neurons. Here I reason that all the results of the efforts of the proponents of the theory can, not only find explanation in the context of the new theory of vision but also provide support for it. This new take of the phenomenon of vision is developed based on the nature of the experimental methods that have succeeded in developing some measure of vision for the blinds, and the inferences from the very likely nature of the computational strategy of the brain. I present evidence that the mental phenomena, which rendered the claim of the mirror neurons, are in essence the results of subjects beings variably touched by their ecology, through the coherent tactile operation of all senses.