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3
INTRODUCTION
1
10
[ "B10", "B9", "B11" ]
17,591,616
pmid-1762151|pmid-16292353|pmid-16176988|pmid-9847079
First, many alien genes are introduced in genomic islands; here, large number of genes arrive from a single donor genome and are physically adjacent.
[ "10", "9", "11" ]
149
6,700
0
false
First, many alien genes are introduced in genomic islands; here, large number of genes arrive from a single donor genome and are physically adjacent.
[]
First, many alien genes are introduced in genomic islands; here, large number of genes arrive from a single donor genome and are physically adjacent.
true
true
true
true
true
1,096
3
INTRODUCTION
1
11
[ "B10", "B9", "B11" ]
17,591,616
pmid-1762151|pmid-16292353|pmid-16176988|pmid-9847079
Second, the non-random distribution of donor genomes for any one recipient (11) increases the likelihood that foreign genes may resemble each other even if they arrived in separate transfer events.
[ "10", "9", "11" ]
197
6,701
1
false
Second, the non-random distribution of donor genomes for any one recipient increases the likelihood that foreign genes may resemble each other even if they arrived in separate transfer events.
[ "11" ]
Second, the non-random distribution of donor genomes for any one recipient increases the likelihood that foreign genes may resemble each other even if they arrived in separate transfer events.
true
true
true
true
true
1,096
3
INTRODUCTION
1
10
[ "B10", "B9", "B11" ]
17,591,616
pmid-1762151|pmid-16292353|pmid-16176988|pmid-9847079
Foreign gene identification by common threshold approaches; native and foreign genes overlap in sequence features.
[ "10", "9", "11" ]
114
6,702
0
false
Foreign gene identification by common threshold approaches; native and foreign genes overlap in sequence features.
[]
Foreign gene identification by common threshold approaches; native and foreign genes overlap in sequence features.
true
true
true
true
true
1,096
3
INTRODUCTION
1
10
[ "B10", "B9", "B11" ]
17,591,616
pmid-1762151|pmid-16292353|pmid-16176988|pmid-9847079
(B) Foreign genes detecting using a clustering approach.
[ "10", "9", "11" ]
56
6,703
0
false
(B) Foreign genes detecting using a clustering approach.
[]
(B) Foreign genes detecting using a clustering approach.
false
false
true
true
false
1,096
3
INTRODUCTION
1
10
[ "B10", "B9", "B11" ]
17,591,616
pmid-1762151|pmid-16292353|pmid-16176988|pmid-9847079
Genes from a single source may have features that overlap with features of genes from other sources, making unambiguous delineation difficult.
[ "10", "9", "11" ]
142
6,704
0
false
Genes from a single source may have features that overlap with features of genes from other sources, making unambiguous delineation difficult.
[]
Genes from a single source may have features that overlap with features of genes from other sources, making unambiguous delineation difficult.
true
true
true
true
true
1,096
3
INTRODUCTION
1
10
[ "B10", "B9", "B11" ]
17,591,616
pmid-1762151|pmid-16292353|pmid-16176988|pmid-9847079
(C) Positional information may be used to accurately classify weakly atypical genes.
[ "10", "9", "11" ]
84
6,705
0
false
(C) Positional information may be used to accurately classify weakly atypical genes.
[]
(C) Positional information may be used to accurately classify weakly atypical genes.
false
false
true
true
false
1,096
3
INTRODUCTION
1
10
[ "B10", "B9", "B11" ]
17,591,616
pmid-1762151|pmid-16292353|pmid-16176988|pmid-9847079
Misclassified genes may be correctly identified using positional information.
[ "10", "9", "11" ]
77
6,706
0
false
Misclassified genes may be correctly identified using positional information.
[]
Misclassified genes may be correctly identified using positional information.
true
true
true
true
true
1,096
4
INTRODUCTION
0
null
null
17,591,616
null
(A) Foreign gene identification by common threshold approaches; native and foreign genes overlap in sequence features.
null
118
6,707
0
false
null
null
(A) Foreign gene identification by common threshold approaches; native and foreign genes overlap in sequence features.
false
false
true
true
false
1,097
4
INTRODUCTION
0
null
null
17,591,616
null
(B) Foreign genes detecting using a clustering approach.
null
56
6,708
0
false
null
null
(B) Foreign genes detecting using a clustering approach.
false
false
true
true
false
1,097
4
INTRODUCTION
0
null
null
17,591,616
null
Genes from a single source may have features that overlap with features of genes from other sources, making unambiguous delineation difficult.
null
142
6,709
0
false
null
null
Genes from a single source may have features that overlap with features of genes from other sources, making unambiguous delineation difficult.
true
true
true
true
true
1,097
4
INTRODUCTION
0
null
null
17,591,616
null
(C) Positional information may be used to accurately classify weakly atypical genes.
null
84
6,710
0
false
null
null
(C) Positional information may be used to accurately classify weakly atypical genes.
false
false
true
true
false
1,097
4
INTRODUCTION
0
null
null
17,591,616
null
Misclassified genes may be correctly identified using positional information.
null
77
6,711
0
false
null
null
Misclassified genes may be correctly identified using positional information.
true
true
true
true
true
1,097
5
INTRODUCTION
1
9
[ "B9" ]
17,591,616
pmid-16292353
Using this information, we have implemented here a 2-fold approach for foreign gene identification.
[ "9" ]
99
6,712
0
false
Using this information, we have implemented here a 2-fold approach for foreign gene identification.
[]
Using this information, we have implemented here a 2-fold approach for foreign gene identification.
true
true
true
true
true
1,098
5
INTRODUCTION
1
9
[ "B9" ]
17,591,616
pmid-16292353
First, we employ a novel gene clustering method based on Jensen–Shannon (JS) divergence measure.
[ "9" ]
96
6,713
0
false
First, we employ a novel gene clustering method based on Jensen–Shannon (JS) divergence measure.
[]
First, we employ a novel gene clustering method based on Jensen–Shannon (JS) divergence measure.
true
true
true
true
true
1,098
5
INTRODUCTION
1
9
[ "B9" ]
17,591,616
pmid-16292353
Contrary to the arbitrary thresholds used by existing parametric methods, this approach segregates genes into distinct classes within a hypothesis testing framework.
[ "9" ]
165
6,714
0
false
Contrary to the arbitrary thresholds used by existing parametric methods, this approach segregates genes into distinct classes within a hypothesis testing framework.
[]
Contrary to the arbitrary thresholds used by existing parametric methods, this approach segregates genes into distinct classes within a hypothesis testing framework.
true
true
true
true
true
1,098
5
INTRODUCTION
1
9
[ "B9" ]
17,591,616
pmid-16292353
In this way, we identify foreign genes not solely by their incongruence with the majority of genes in the genome but also by their similarity to each other (Figure 1B).
[ "9" ]
168
6,715
0
false
In this way, we identify foreign genes not solely by their incongruence with the majority of genes in the genome but also by their similarity to each other (Figure 1B).
[]
In this way, we identify foreign genes not solely by their incongruence with the majority of genes in the genome but also by their similarity to each other (Figure 1B).
true
true
true
true
true
1,098
5
INTRODUCTION
1
9
[ "B9" ]
17,591,616
pmid-16292353
Yet even here, we would expect that somewhat atypical native genes may be misclassified as alien, and vice versa.
[ "9" ]
113
6,716
0
false
Yet even here, we would expect that somewhat atypical native genes may be misclassified as alien, and vice versa.
[]
Yet even here, we would expect that somewhat atypical native genes may be misclassified as alien, and vice versa.
true
true
true
true
true
1,098
5
INTRODUCTION
1
9
[ "B9" ]
17,591,616
pmid-16292353
To escape the limitations imposed by any single threshold in classifying genes with ambiguous features, we use genome position information to reassign genes between native and foreign classes based on the characteristics of physically adjacent genes (Figure 1C).
[ "9" ]
262
6,717
0
false
To escape the limitations imposed by any single threshold in classifying genes with ambiguous features, we use genome position information to reassign genes between native and foreign classes based on the characteristics of physically adjacent genes (Figure 1C).
[]
To escape the limitations imposed by any single threshold in classifying genes with ambiguous features, we use genome position information to reassign genes between native and foreign classes based on the characteristics of physically adjacent genes (Figure 1C).
true
true
true
true
true
1,098
5
INTRODUCTION
1
9
[ "B9" ]
17,591,616
pmid-16292353
The performance of this approach was assessed on a test platform of artificial chimeric genomes (9) and then applied to well-understood Escherichia coli K12 genome.
[ "9" ]
164
6,718
1
false
The performance of this approach was assessed on a test platform of artificial chimeric genomes and then applied to well-understood Escherichia coli K12 genome.
[ "9" ]
The performance of this approach was assessed on a test platform of artificial chimeric genomes and then applied to well-understood Escherichia coli K12 genome.
true
true
true
true
true
1,098
0
DISCUSSION
1
9
[ "B9" ]
17,591,616
pmid-10381871|pmid-10508729|pmid-10830951|pmid-16292353
Current parametric methods select a threshold to discriminate between foreign and native genes.
[ "9" ]
95
6,719
0
false
Current parametric methods select a threshold to discriminate between foreign and native genes.
[]
Current parametric methods select a threshold to discriminate between foreign and native genes.
true
true
true
true
true
1,099
0
DISCUSSION
1
9
[ "B9" ]
17,591,616
pmid-10381871|pmid-10508729|pmid-10830951|pmid-16292353
While these thresholds are often arbitrary, our proposed entropic clustering method discriminates between the gene classes in the framework of statistical significance.
[ "9" ]
168
6,720
0
false
While these thresholds are often arbitrary, our proposed entropic clustering method discriminates between the gene classes in the framework of statistical significance.
[]
While these thresholds are often arbitrary, our proposed entropic clustering method discriminates between the gene classes in the framework of statistical significance.
true
true
true
true
true
1,099
0
DISCUSSION
1
9
[ "B9" ]
17,591,616
pmid-10381871|pmid-10508729|pmid-10830951|pmid-16292353
As a caveat, there are multiple hypothesis testing problems involved, namely the repetition of the test in each iteration step and over the hierarchy.
[ "9" ]
150
6,721
0
false
As a caveat, there are multiple hypothesis testing problems involved, namely the repetition of the test in each iteration step and over the hierarchy.
[]
As a caveat, there are multiple hypothesis testing problems involved, namely the repetition of the test in each iteration step and over the hierarchy.
true
true
true
true
true
1,099
0
DISCUSSION
1
9
[ "B9" ]
17,591,616
pmid-10381871|pmid-10508729|pmid-10830951|pmid-16292353
Therefore, appropriately stringent thresholds must be chosen to compensate for multiple tests.
[ "9" ]
94
6,722
0
false
Therefore, appropriately stringent thresholds must be chosen to compensate for multiple tests.
[]
Therefore, appropriately stringent thresholds must be chosen to compensate for multiple tests.
true
true
true
true
true
1,099
0
DISCUSSION
1
9
[ "B9" ]
17,591,616
pmid-10381871|pmid-10508729|pmid-10830951|pmid-16292353
Although sporadic rejection of the null hypothesis when using multiple tests results in failure to merge classes, these classes may be merged in subsequent steps using positional information.
[ "9" ]
191
6,723
0
false
Although sporadic rejection of the null hypothesis when using multiple tests results in failure to merge classes, these classes may be merged in subsequent steps using positional information.
[]
Although sporadic rejection of the null hypothesis when using multiple tests results in failure to merge classes, these classes may be merged in subsequent steps using positional information.
true
true
true
true
true
1,099
0
DISCUSSION
1
9
[ "B9" ]
17,591,616
pmid-10381871|pmid-10508729|pmid-10830951|pmid-16292353
Although the AIC-based approach we introduced earlier (9) also has a strong theoretical underpinning, the thresholds in the generalized AIC cannot be rigorously described.
[ "9" ]
171
6,724
1
false
Although the AIC-based approach we introduced earlier also has a strong theoretical underpinning, the thresholds in the generalized AIC cannot be rigorously described.
[ "9" ]
Although the AIC-based approach we introduced earlier also has a strong theoretical underpinning, the thresholds in the generalized AIC cannot be rigorously described.
true
true
true
true
true
1,099
0
DISCUSSION
1
9
[ "B9" ]
17,591,616
pmid-10381871|pmid-10508729|pmid-10830951|pmid-16292353
Among the parametric methods of foreign gene detection, to our knowledge, the JS clustering methods are the only methods that classify atypical genes in the framework of statistical significance.
[ "9" ]
195
6,725
0
false
Among the parametric methods of foreign gene detection, to our knowledge, the JS clustering methods are the only methods that classify atypical genes in the framework of statistical significance.
[]
Among the parametric methods of foreign gene detection, to our knowledge, the JS clustering methods are the only methods that classify atypical genes in the framework of statistical significance.
true
true
true
true
true
1,099
1
DISCUSSION
0
null
null
17,591,616
pmid-11470360|pmid-12975657|pmid-15913459
A shortcoming of parametric methods is their difficulty in identifying weakly atypical genes.
null
93
6,726
0
false
null
null
A shortcoming of parametric methods is their difficulty in identifying weakly atypical genes.
true
true
true
true
true
1,100
1
DISCUSSION
0
null
null
17,591,616
pmid-11470360|pmid-12975657|pmid-15913459
The trade-off is clear: classifying only strongly atypical genes as foreign decreases false predictions, however, this comes at the expense of many foreign genes misclassified as native, a more relaxed criteria increases the sensitivity of a method at the expense of false predictions.
null
285
6,727
0
false
null
null
The trade-off is clear: classifying only strongly atypical genes as foreign decreases false predictions, however, this comes at the expense of many foreign genes misclassified as native, a more relaxed criteria increases the sensitivity of a method at the expense of false predictions.
true
true
true
true
true
1,100
1
DISCUSSION
0
null
null
17,591,616
pmid-11470360|pmid-12975657|pmid-15913459
This inherent weakness limits the abilities of this class of methods.
null
69
6,728
0
false
null
null
This inherent weakness limits the abilities of this class of methods.
true
true
true
true
true
1,100
1
DISCUSSION
0
null
null
17,591,616
pmid-11470360|pmid-12975657|pmid-15913459
Through this study, we propose gene context information as a means to address this issue.
null
89
6,729
0
false
null
null
Through this study, we propose gene context information as a means to address this issue.
true
true
true
true
true
1,100
1
DISCUSSION
0
null
null
17,591,616
pmid-11470360|pmid-12975657|pmid-15913459
The utility of positional information increases when the confidence of typical and atypical gene classes increases.
null
115
6,730
0
false
null
null
The utility of positional information increases when the confidence of typical and atypical gene classes increases.
true
true
true
true
true
1,100
1
DISCUSSION
0
null
null
17,591,616
pmid-11470360|pmid-12975657|pmid-15913459
That is, optimal assignment occurs at higher stringencies ensuring the purity of both typical and atypical gene classes, at the expense of creating a larger number of classes.
null
175
6,731
0
false
null
null
That is, optimal assignment occurs at higher stringencies ensuring the purity of both typical and atypical gene classes, at the expense of creating a larger number of classes.
true
true
true
true
true
1,100
1
DISCUSSION
0
null
null
17,591,616
pmid-11470360|pmid-12975657|pmid-15913459
In a two pronged approach (class reassignment followed by class refinement), the misclassification of foreign genes was reduced by allowing weakly atypical native genes to join the native gene class by virtue of their positions, not by relaxing the criteria for class merger.
null
275
6,732
0
false
null
null
In a two pronged approach (class reassignment followed by class refinement), the misclassification of foreign genes was reduced by allowing weakly atypical native genes to join the native gene class by virtue of their positions, not by relaxing the criteria for class merger.
true
true
true
true
true
1,100
1
DISCUSSION
0
null
null
17,591,616
pmid-11470360|pmid-12975657|pmid-15913459
This also serves to reduce the misclassification of native genes as weakly atypical foreign genes join their classes in a similar fashion (Supplementary Table 4).
null
162
6,733
0
false
null
null
This also serves to reduce the misclassification of native genes as weakly atypical foreign genes join their classes in a similar fashion (Supplementary Table 4).
true
true
true
true
true
1,100
2
DISCUSSION
0
null
null
17,591,616
pmid-9089078|pmid-9689094|pmid-11470360|pmid-16292353
We also observed that positional information works synergistically with gene clustering methods reducing the classification errors better than for methods which classify the genes only as native and foreign (Table 2).
null
217
6,734
0
false
null
null
We also observed that positional information works synergistically with gene clustering methods reducing the classification errors better than for methods which classify the genes only as native and foreign (Table 2).
true
true
true
true
true
1,101
2
DISCUSSION
0
null
null
17,591,616
pmid-9089078|pmid-9689094|pmid-11470360|pmid-16292353
To examine this further, we carried out numerical experiments where genes from all the small classes generated by JS-CB were pooled as a single foreign class and the largest class represented native genes.
null
205
6,735
0
false
null
null
To examine this further, we carried out numerical experiments where genes from all the small classes generated by JS-CB were pooled as a single foreign class and the largest class represented native genes.
true
true
true
true
true
1,101
2
DISCUSSION
0
null
null
17,591,616
pmid-9089078|pmid-9689094|pmid-11470360|pmid-16292353
Class refinement was then done using the positional information of genes.
null
73
6,736
0
false
null
null
Class refinement was then done using the positional information of genes.
true
true
true
true
true
1,101
2
DISCUSSION
0
null
null
17,591,616
pmid-9089078|pmid-9689094|pmid-11470360|pmid-16292353
By minimizing the mean error over the parameter space of the method, comparison was made with cases when class refinement was done for all method-generated classes and also when full power of positional information (both class reassignment and refinement) was used for these classes (Supplementary Table 5).
null
307
6,737
0
false
null
null
By minimizing the mean error over the parameter space of the method, comparison was made with cases when class refinement was done for all method-generated classes and also when full power of positional information (both class reassignment and refinement) was used for these classes (Supplementary Table 5).
true
true
true
true
true
1,101
2
DISCUSSION
0
null
null
17,591,616
pmid-9089078|pmid-9689094|pmid-11470360|pmid-16292353
The Type II error decreased significantly causing a decrease in mean error when class refinement was performed on all method- generated classes as opposed to two classes (typical and atypical).
null
193
6,738
0
false
null
null
The Type II error decreased significantly causing a decrease in mean error when class refinement was performed on all method- generated classes as opposed to two classes (typical and atypical).
true
true
true
true
true
1,101
2
DISCUSSION
0
null
null
17,591,616
pmid-9089078|pmid-9689094|pmid-11470360|pmid-16292353
Both Type I error and Type II error decreased remarkably when class reassignment followed by class refinement was done at strict stringencies.
null
142
6,739
0
false
null
null
Both Type I error and Type II error decreased remarkably when class reassignment followed by class refinement was done at strict stringencies.
true
true
true
true
true
1,101
2
DISCUSSION
0
null
null
17,591,616
pmid-9089078|pmid-9689094|pmid-11470360|pmid-16292353
In addition, since JS methods effectively group genes from common donors (Figure 3), they may be useful in helping identify potential donors for foreign genes in bacterial genomes.
null
180
6,740
0
false
null
null
In addition, since JS methods effectively group genes from common donors (Figure 3), they may be useful in helping identify potential donors for foreign genes in bacterial genomes.
true
true
true
true
true
1,101
3
DISCUSSION
1
19
[ "B19" ]
17,591,616
pmid-1762151|pmid-16292353|pmid-16176988|pmid-9847079
Hayes and Borodovsky (19) developed a k-means algorithm for partitioning a gene-set into primarily two classes (k = 2).
[ "19" ]
119
6,741
1
false
Hayes and Borodovsky developed a k-means algorithm for partitioning a gene-set into primarily two classes (k = 2).
[ "19" ]
Hayes and Borodovsky developed a k-means algorithm for partitioning a gene-set into primarily two classes (k = 2).
true
true
true
true
true
1,102
3
DISCUSSION
1
19
[ "B19" ]
17,591,616
pmid-1762151|pmid-16292353|pmid-16176988|pmid-9847079
The gene models trained on these classes were then incorporated in a prokaryotic gene finder, GeneMark-genesis, where the use of two gene classes improved considerably the identification of genes, particularly those with atypical composition.
[ "19" ]
242
6,742
0
false
The gene models trained on these classes were then incorporated in a prokaryotic gene finder, GeneMark-genesis, where the use of two gene classes improved considerably the identification of genes, particularly those with atypical composition.
[]
The gene models trained on these classes were then incorporated in a prokaryotic gene finder, GeneMark-genesis, where the use of two gene classes improved considerably the identification of genes, particularly those with atypical composition.
true
true
true
true
true
1,102
3
DISCUSSION
1
19
[ "B19" ]
17,591,616
pmid-1762151|pmid-16292353|pmid-16176988|pmid-9847079
The success of such prediction algorithms critically depends on the purity of the gene classes.
[ "19" ]
95
6,743
0
false
The success of such prediction algorithms critically depends on the purity of the gene classes.
[]
The success of such prediction algorithms critically depends on the purity of the gene classes.
true
true
true
true
true
1,102
3
DISCUSSION
1
19
[ "B19" ]
17,591,616
pmid-1762151|pmid-16292353|pmid-16176988|pmid-9847079
The value of ‘k’ is not known a priori and k = 2 may not be best option to model genic complexity, as shown by our experiments on chimeric artificial as well as genuine genomes.
[ "19" ]
177
6,744
0
false
The value of ‘k’ is not known a priori and k = 2 may not be best option to model genic complexity, as shown by our experiments on chimeric artificial as well as genuine genomes.
[]
The value of ‘k’ is not known a priori and k = 2 may not be best option to model genic complexity, as shown by our experiments on chimeric artificial as well as genuine genomes.
true
true
true
true
true
1,102
3
DISCUSSION
1
19
[ "B19" ]
17,591,616
pmid-1762151|pmid-16292353|pmid-16176988|pmid-9847079
Our hierarchical agglomerative gene-clustering algorithm provides a solution: gene classes grow logically starting with single genes and the process is halted when the distinction between the gene classes is deemed statistically significant.
[ "19" ]
241
6,745
0
false
Our hierarchical agglomerative gene-clustering algorithm provides a solution: gene classes grow logically starting with single genes and the process is halted when the distinction between the gene classes is deemed statistically significant.
[]
Our hierarchical agglomerative gene-clustering algorithm provides a solution: gene classes grow logically starting with single genes and the process is halted when the distinction between the gene classes is deemed statistically significant.
true
true
true
true
true
1,102
3
DISCUSSION
1
19
[ "B19" ]
17,591,616
pmid-1762151|pmid-16292353|pmid-16176988|pmid-9847079
Native genes are identified as belonging to the single largest class that has typically ∼60–95% of the total genes, and foreign genes are divided into several small classes.
[ "19" ]
173
6,746
0
false
Native genes are identified as belonging to the single largest class that has typically ∼60–95% of the total genes, and foreign genes are divided into several small classes.
[]
Native genes are identified as belonging to the single largest class that has typically ∼60–95% of the total genes, and foreign genes are divided into several small classes.
true
true
true
true
true
1,102
3
DISCUSSION
1
19
[ "B19" ]
17,591,616
pmid-1762151|pmid-16292353|pmid-16176988|pmid-9847079
It should be possible to build a gene model for each gene class, which will likely improve the accuracy of gene identification.
[ "19" ]
127
6,747
0
false
It should be possible to build a gene model for each gene class, which will likely improve the accuracy of gene identification.
[]
It should be possible to build a gene model for each gene class, which will likely improve the accuracy of gene identification.
true
true
true
true
true
1,102
0
INTRODUCTION
1
1
[ "b1", "b2", "b3", "b4", "b5" ]
16,822,856
pmid-1620105|pmid-11039937|pmid-10805797|pmid-15563511|pmid-15521053|pmid-9537413|pmid-12089561
The correction of mutations in genomic DNA in situ is one of the most attractive approaches for gene therapy of inherited single gene disorders.
[ "1", "2", "3", "4", "5" ]
144
6,748
0
false
The correction of mutations in genomic DNA in situ is one of the most attractive approaches for gene therapy of inherited single gene disorders.
[]
The correction of mutations in genomic DNA in situ is one of the most attractive approaches for gene therapy of inherited single gene disorders.
true
true
true
true
true
1,103
0
INTRODUCTION
1
1
[ "b1", "b2", "b3", "b4", "b5" ]
16,822,856
pmid-1620105|pmid-11039937|pmid-10805797|pmid-15563511|pmid-15521053|pmid-9537413|pmid-12089561
This process is inherently non-mutagenic and very likely to conserve appropriately regulated expression of the repaired gene product.
[ "1", "2", "3", "4", "5" ]
133
6,749
0
false
This process is inherently non-mutagenic and very likely to conserve appropriately regulated expression of the repaired gene product.
[]
This process is inherently non-mutagenic and very likely to conserve appropriately regulated expression of the repaired gene product.
true
true
true
true
true
1,103
0
INTRODUCTION
1
1
[ "b1", "b2", "b3", "b4", "b5" ]
16,822,856
pmid-1620105|pmid-11039937|pmid-10805797|pmid-15563511|pmid-15521053|pmid-9537413|pmid-12089561
Gene targeting through homologous recombination (HR) is the most accurate and versatile mechanism for such correction.
[ "1", "2", "3", "4", "5" ]
118
6,750
0
false
Gene targeting through homologous recombination (HR) is the most accurate and versatile mechanism for such correction.
[]
Gene targeting through homologous recombination (HR) is the most accurate and versatile mechanism for such correction.
true
true
true
true
true
1,103
0
INTRODUCTION
1
1
[ "b1", "b2", "b3", "b4", "b5" ]
16,822,856
pmid-1620105|pmid-11039937|pmid-10805797|pmid-15563511|pmid-15521053|pmid-9537413|pmid-12089561
However, HR occurs in human somatic cells with very low frequencies of about 10−7 (1).
[ "1", "2", "3", "4", "5" ]
86
6,751
1
false
However, HR occurs in human somatic cells with very low frequencies of about 10−7.
[ "1" ]
However, HR occurs in human somatic cells with very low frequencies of about 10−7.
true
true
true
true
true
1,103
0
INTRODUCTION
1
1
[ "b1", "b2", "b3", "b4", "b5" ]
16,822,856
pmid-1620105|pmid-11039937|pmid-10805797|pmid-15563511|pmid-15521053|pmid-9537413|pmid-12089561
Efforts directed towards improving the frequency of gene repair have lead to the development of numerous oligonucleotide-based strategies, involving delivery of plain DNA by transfection or injection.
[ "1", "2", "3", "4", "5" ]
200
6,752
0
false
Efforts directed towards improving the frequency of gene repair have lead to the development of numerous oligonucleotide-based strategies, involving delivery of plain DNA by transfection or injection.
[]
Efforts directed towards improving the frequency of gene repair have lead to the development of numerous oligonucleotide-based strategies, involving delivery of plain DNA by transfection or injection.
true
true
true
true
true
1,103
0
INTRODUCTION
1
1
[ "b1", "b2", "b3", "b4", "b5" ]
16,822,856
pmid-1620105|pmid-11039937|pmid-10805797|pmid-15563511|pmid-15521053|pmid-9537413|pmid-12089561
Triplex-forming oligonucleotides (TFOs) can induce recombination between a polypurine/polypyrimidine rich DNA duplex and unlinked donor molecule by introducing damage to such duplex.
[ "1", "2", "3", "4", "5" ]
182
6,753
0
false
Triplex-forming oligonucleotides (TFOs) can induce recombination between a polypurine/polypyrimidine rich DNA duplex and unlinked donor molecule by introducing damage to such duplex.
[]
Triplex-forming oligonucleotides (TFOs) can induce recombination between a polypurine/polypyrimidine rich DNA duplex and unlinked donor molecule by introducing damage to such duplex.
true
true
true
true
true
1,103
0
INTRODUCTION
1
2
[ "b1", "b2", "b3", "b4", "b5" ]
16,822,856
pmid-1620105|pmid-11039937|pmid-10805797|pmid-15563511|pmid-15521053|pmid-9537413|pmid-12089561
The maximum frequency of targeted modification achieved with TFOs in vivo was 10−4 (2).
[ "1", "2", "3", "4", "5" ]
87
6,754
1
false
The maximum frequency of targeted modification achieved with TFOs in vivo was 10−4.
[ "2" ]
The maximum frequency of targeted modification achieved with TFOs in vivo was 10−4.
true
true
true
true
true
1,103
0
INTRODUCTION
1
3
[ "b1", "b2", "b3", "b4", "b5" ]
16,822,856
pmid-1620105|pmid-11039937|pmid-10805797|pmid-15563511|pmid-15521053|pmid-9537413|pmid-12089561
Alternatively, the best frequency for gene editing with chimeric RNA-DNA oligonucleotides (RDOs) or chimeraplasts was 1% of all muscle fibers positive for the chimeraplast DNA mostly close to the injection site (3).
[ "1", "2", "3", "4", "5" ]
215
6,755
1
false
Alternatively, the best frequency for gene editing with chimeric RNA-DNA oligonucleotides (RDOs) or chimeraplasts was 1% of all muscle fibers positive for the chimeraplast DNA mostly close to the injection site.
[ "3" ]
Alternatively, the best frequency for gene editing with chimeric RNA-DNA oligonucleotides (RDOs) or chimeraplasts was 1% of all muscle fibers positive for the chimeraplast DNA mostly close to the injection site.
true
true
true
true
true
1,103
0
INTRODUCTION
1
4
[ "b1", "b2", "b3", "b4", "b5" ]
16,822,856
pmid-1620105|pmid-11039937|pmid-10805797|pmid-15563511|pmid-15521053|pmid-9537413|pmid-12089561
Chimeraplast and single-stranded oligodeoxynucleotide-mediated gene repair (4) most likely involves a mismatch repair mechanism and is restricted to repair of point mutations.
[ "1", "2", "3", "4", "5" ]
175
6,756
1
false
Chimeraplast and single-stranded oligodeoxynucleotide-mediated gene repair most likely involves a mismatch repair mechanism and is restricted to repair of point mutations.
[ "4" ]
Chimeraplast and single-stranded oligodeoxynucleotide-mediated gene repair most likely involves a mismatch repair mechanism and is restricted to repair of point mutations.
true
true
true
true
true
1,103
0
INTRODUCTION
1
1
[ "b1", "b2", "b3", "b4", "b5" ]
16,822,856
pmid-1620105|pmid-11039937|pmid-10805797|pmid-15563511|pmid-15521053|pmid-9537413|pmid-12089561
A major limitation of the ability of injected chimeraplast to promote gene conversion in muscle appears to be the restricted uptake of chimeraplasts into fibers due to inefficient delivery of the repair substrate in vivo.
[ "1", "2", "3", "4", "5" ]
221
6,757
0
false
A major limitation of the ability of injected chimeraplast to promote gene conversion in muscle appears to be the restricted uptake of chimeraplasts into fibers due to inefficient delivery of the repair substrate in vivo.
[]
A major limitation of the ability of injected chimeraplast to promote gene conversion in muscle appears to be the restricted uptake of chimeraplasts into fibers due to inefficient delivery of the repair substrate in vivo.
true
true
true
true
true
1,103
0
INTRODUCTION
1
5
[ "b1", "b2", "b3", "b4", "b5" ]
16,822,856
pmid-1620105|pmid-11039937|pmid-10805797|pmid-15563511|pmid-15521053|pmid-9537413|pmid-12089561
A short-fragment homologous replacement (SFHR) strategy allows alteration of as many as 4 bp, with a maximum reported frequency of about 0.4% (5).
[ "1", "2", "3", "4", "5" ]
146
6,758
1
false
A short-fragment homologous replacement (SFHR) strategy allows alteration of as many as 4 bp, with a maximum reported frequency of about 0.4%.
[ "5" ]
A short-fragment homologous replacement (SFHR) strategy allows alteration of as many as 4 bp, with a maximum reported frequency of about 0.4%.
true
true
true
true
true
1,103
1
INTRODUCTION
1
6
[ "b6", "b7", "b8", "b9", "b10", "b11", "b12", "b13", "b14" ]
16,822,856
pmid-2725520|pmid-12109211|pmid-15932801|pmid-16261169|pmid-14732747|pmid-14704360|pmid-15950905|pmid-12833043|pmid-12778174|pmid-16261169
Viral delivery systems based on retrovirus, adenovirus and adeno-associated virus (AAV) overcome some of these limitations by offering more efficient DNA delivery and by accommodating longer stretches of homology with the genomic locus to allow a broad spectrum of targeted modifications.
[ "6", "7", "8", "9", "10", "11", "12", "13", "14" ]
288
6,759
0
false
Viral delivery systems based on retrovirus, adenovirus and adeno-associated virus (AAV) overcome some of these limitations by offering more efficient DNA delivery and by accommodating longer stretches of homology with the genomic locus to allow a broad spectrum of targeted modifications.
[]
Viral delivery systems based on retrovirus, adenovirus and adeno-associated virus (AAV) overcome some of these limitations by offering more efficient DNA delivery and by accommodating longer stretches of homology with the genomic locus to allow a broad spectrum of targeted modifications.
true
true
true
true
true
1,104
1
INTRODUCTION
1
6
[ "b6", "b7", "b8", "b9", "b10", "b11", "b12", "b13", "b14" ]
16,822,856
pmid-2725520|pmid-12109211|pmid-15932801|pmid-16261169|pmid-14732747|pmid-14704360|pmid-15950905|pmid-12833043|pmid-12778174|pmid-16261169
The best targeting frequencies achieved by retrovirus and adenovirus vectors, however, were only comparable to those shown by DNA transfection (6,7).
[ "6", "7", "8", "9", "10", "11", "12", "13", "14" ]
149
6,760
0
false
The best targeting frequencies achieved by retrovirus and adenovirus vectors, however, were only comparable to those shown by DNA transfection.
[ "6,7" ]
The best targeting frequencies achieved by retrovirus and adenovirus vectors, however, were only comparable to those shown by DNA transfection.
true
true
true
true
true
1,104
1
INTRODUCTION
1
6
[ "b6", "b7", "b8", "b9", "b10", "b11", "b12", "b13", "b14" ]
16,822,856
pmid-2725520|pmid-12109211|pmid-15932801|pmid-16261169|pmid-14732747|pmid-14704360|pmid-15950905|pmid-12833043|pmid-12778174|pmid-16261169
In contrast, recombinant adeno-associated virus (rAAV) vectors comprised of single-stranded DNA with unique inverted terminal repeats (ITRs), reach the nucleus in multiple copies and have been shown to target homologous sequences in cultured human cells with an efficiency of up to 1% [reviewed in (8,9)].
[ "6", "7", "8", "9", "10", "11", "12", "13", "14" ]
305
6,761
0
false
In contrast, recombinant adeno-associated virus (rAAV) vectors comprised of single-stranded DNA with unique inverted terminal repeats (ITRs), reach the nucleus in multiple copies and have been shown to target homologous sequences in cultured human cells with an efficiency of up to 1%.
[ "reviewed in (8,9)" ]
In contrast, recombinant adeno-associated virus (rAAV) vectors comprised of single-stranded DNA with unique inverted terminal repeats (ITRs), reach the nucleus in multiple copies and have been shown to target homologous sequences in cultured human cells with an efficiency of up to 1%.
true
true
true
true
true
1,104
1
INTRODUCTION
1
10
[ "b6", "b7", "b8", "b9", "b10", "b11", "b12", "b13", "b14" ]
16,822,856
pmid-2725520|pmid-12109211|pmid-15932801|pmid-16261169|pmid-14732747|pmid-14704360|pmid-15950905|pmid-12833043|pmid-12778174|pmid-16261169
This property of rAAV combined with its broad host range, the availability of multiple virus serotypes and recent advancements in viral re-targeting through capsid manipulation (10) make rAAV an attractive system for gene correction and, alternatively, for gene disruption aimed at generating knock-outs in cultured huma...
[ "6", "7", "8", "9", "10", "11", "12", "13", "14" ]
358
6,762
1
false
This property of rAAV combined with its broad host range, the availability of multiple virus serotypes and recent advancements in viral re-targeting through capsid manipulation make rAAV an attractive system for gene correction and, alternatively, for gene disruption aimed at generating knock-outs in cultured human pri...
[ "10", "11,12" ]
This property of rAAV combined with its broad host range, the availability of multiple virus serotypes and recent advancements in viral re-targeting through capsid manipulation make rAAV an attractive system for gene correction and, alternatively, for gene disruption aimed at generating knock-outs in cultured human pri...
true
true
true
true
true
1,104
1
INTRODUCTION
1
6
[ "b6", "b7", "b8", "b9", "b10", "b11", "b12", "b13", "b14" ]
16,822,856
pmid-2725520|pmid-12109211|pmid-15932801|pmid-16261169|pmid-14732747|pmid-14704360|pmid-15950905|pmid-12833043|pmid-12778174|pmid-16261169
Still, the rate of AAV-mediated gene targeting alone is not sufficiently high for gene therapy through gene correction in vivo, where the accompanying potentially mutagenic random integration events cannot be selected against.
[ "6", "7", "8", "9", "10", "11", "12", "13", "14" ]
226
6,763
0
false
Still, the rate of AAV-mediated gene targeting alone is not sufficiently high for gene therapy through gene correction in vivo, where the accompanying potentially mutagenic random integration events cannot be selected against.
[]
Still, the rate of AAV-mediated gene targeting alone is not sufficiently high for gene therapy through gene correction in vivo, where the accompanying potentially mutagenic random integration events cannot be selected against.
true
true
true
true
true
1,104
1
INTRODUCTION
1
6
[ "b6", "b7", "b8", "b9", "b10", "b11", "b12", "b13", "b14" ]
16,822,856
pmid-2725520|pmid-12109211|pmid-15932801|pmid-16261169|pmid-14732747|pmid-14704360|pmid-15950905|pmid-12833043|pmid-12778174|pmid-16261169
In cell culture, the rate of random integration was at 10%, and integration in vivo is known to occur predominantly in transcriptionally active genes (13,14).
[ "6", "7", "8", "9", "10", "11", "12", "13", "14" ]
158
6,764
0
false
In cell culture, the rate of random integration was at 10%, and integration in vivo is known to occur predominantly in transcriptionally active genes.
[ "13,14" ]
In cell culture, the rate of random integration was at 10%, and integration in vivo is known to occur predominantly in transcriptionally active genes.
true
true
true
true
true
1,104
2
INTRODUCTION
1
15
[ "b15", "b16", "b17", "b18" ]
16,822,856
pmid-12724414|pmid-12724413|pmid-12663782|pmid-11711618|pmid-7855602|pmid-11782437|pmid-3347204|pmid-8805304
Similar to conventional gene targeting the frequency of rAAV-mediated targeting was elevated significantly by the introduction of DNA double-strand breaks (DSBs) at the targeted site (15,16).
[ "15", "16", "17", "18" ]
191
6,765
0
false
Similar to conventional gene targeting the frequency of rAAV-mediated targeting was elevated significantly by the introduction of DNA double-strand breaks (DSBs) at the targeted site.
[ "15,16" ]
Similar to conventional gene targeting the frequency of rAAV-mediated targeting was elevated significantly by the introduction of DNA double-strand breaks (DSBs) at the targeted site.
true
true
true
true
true
1,105
2
INTRODUCTION
1
15
[ "b15", "b16", "b17", "b18" ]
16,822,856
pmid-12724414|pmid-12724413|pmid-12663782|pmid-11711618|pmid-7855602|pmid-11782437|pmid-3347204|pmid-8805304
This supports the hypothesis that components of DSB repair pathways, such as non-homologous end-joining (NHEJ) or HR are involved in rAAV-mediated gene targeting.
[ "15", "16", "17", "18" ]
162
6,766
0
false
This supports the hypothesis that components of DSB repair pathways, such as non-homologous end-joining (NHEJ) or HR are involved in rAAV-mediated gene targeting.
[]
This supports the hypothesis that components of DSB repair pathways, such as non-homologous end-joining (NHEJ) or HR are involved in rAAV-mediated gene targeting.
true
true
true
true
true
1,105
2
INTRODUCTION
1
17
[ "b15", "b16", "b17", "b18" ]
16,822,856
pmid-12724414|pmid-12724413|pmid-12663782|pmid-11711618|pmid-7855602|pmid-11782437|pmid-3347204|pmid-8805304
Studies in SCID mice suggest that DNA-PK promotes circularization of linear double-stranded rAAV genomes (17).
[ "15", "16", "17", "18" ]
110
6,767
1
false
Studies in SCID mice suggest that DNA-PK promotes circularization of linear double-stranded rAAV genomes.
[ "17" ]
Studies in SCID mice suggest that DNA-PK promotes circularization of linear double-stranded rAAV genomes.
true
true
true
true
true
1,105
2
INTRODUCTION
1
18
[ "b15", "b16", "b17", "b18" ]
16,822,856
pmid-12724414|pmid-12724413|pmid-12663782|pmid-11711618|pmid-7855602|pmid-11782437|pmid-3347204|pmid-8805304
It has also been shown that proteins involved in both NHEJ and HR, such as KU86 and RAD52 bind to the AAV genome and affect the transduction efficiency, possibly via a modification of AAV DNA processing (18).
[ "15", "16", "17", "18" ]
208
6,768
1
false
It has also been shown that proteins involved in both NHEJ and HR, such as KU86 and RAD52 bind to the AAV genome and affect the transduction efficiency, possibly via a modification of AAV DNA processing.
[ "18" ]
It has also been shown that proteins involved in both NHEJ and HR, such as KU86 and RAD52 bind to the AAV genome and affect the transduction efficiency, possibly via a modification of AAV DNA processing.
true
true
true
true
true
1,105
2
INTRODUCTION
1
15
[ "b15", "b16", "b17", "b18" ]
16,822,856
pmid-12724414|pmid-12724413|pmid-12663782|pmid-11711618|pmid-7855602|pmid-11782437|pmid-3347204|pmid-8805304
However, it remains unclear which pathway and proteins mediate gene targeting by rAAV.
[ "15", "16", "17", "18" ]
86
6,769
0
false
However, it remains unclear which pathway and proteins mediate gene targeting by rAAV.
[]
However, it remains unclear which pathway and proteins mediate gene targeting by rAAV.
true
true
true
true
true
1,105
3
INTRODUCTION
1
19
[ "b19", "b20" ]
16,822,856
pmid-10775597|pmid-8627803|pmid-12663782|pmid-11711618|pmid-10775597
The unique structure of the rAAV vector DNA with an unusually short stretch of double-stranded (ds) DNA transitioning into the extended single-strand region between the ITRs, was found to be important for targeting.
[ "19", "20" ]
215
6,770
0
false
The unique structure of the rAAV vector DNA with an unusually short stretch of double-stranded (ds) DNA transitioning into the extended single-strand region between the ITRs, was found to be important for targeting.
[]
The unique structure of the rAAV vector DNA with an unusually short stretch of double-stranded (ds) DNA transitioning into the extended single-strand region between the ITRs, was found to be important for targeting.
true
true
true
true
true
1,106
3
INTRODUCTION
1
19
[ "b19", "b20" ]
16,822,856
pmid-10775597|pmid-8627803|pmid-12663782|pmid-11711618|pmid-10775597
Addition of self-complementary double-stranded genomes to the native single-stranded rAAV DNA did not improve the targeting reaction, and dimeric vector molecules, which do not contain the characteristic ITRs and ss–dsDNA transition regions, failed to target efficiently (19).
[ "19", "20" ]
276
6,771
1
false
Addition of self-complementary double-stranded genomes to the native single-stranded rAAV DNA did not improve the targeting reaction, and dimeric vector molecules, which do not contain the characteristic ITRs and ss–dsDNA transition regions, failed to target efficiently.
[ "19" ]
Addition of self-complementary double-stranded genomes to the native single-stranded rAAV DNA did not improve the targeting reaction, and dimeric vector molecules, which do not contain the characteristic ITRs and ss–dsDNA transition regions, failed to target efficiently.
true
true
true
true
true
1,106
3
INTRODUCTION
1
20
[ "b19", "b20" ]
16,822,856
pmid-10775597|pmid-8627803|pmid-12663782|pmid-11711618|pmid-10775597
The largely single-stranded genomes represent the majority of vector forms in the infected cell for several days (20), a period of time that should be sufficient for targeting reactions to occur.
[ "19", "20" ]
195
6,772
1
false
The largely single-stranded genomes represent the majority of vector forms in the infected cell for several days, a period of time that should be sufficient for targeting reactions to occur.
[ "20" ]
The largely single-stranded genomes represent the majority of vector forms in the infected cell for several days, a period of time that should be sufficient for targeting reactions to occur.
true
true
true
true
true
1,106
3
INTRODUCTION
1
19
[ "b19", "b20" ]
16,822,856
pmid-10775597|pmid-8627803|pmid-12663782|pmid-11711618|pmid-10775597
Therefore, DNA repair factors or protein complexes involved in the cellular pathways of processing of ssDNA of specific DNA structures, such as ITRs, or of ss–ds transitional regions might be key to gene targeting by rAAV.
[ "19", "20" ]
222
6,773
0
false
Therefore, DNA repair factors or protein complexes involved in the cellular pathways of processing of ssDNA of specific DNA structures, such as ITRs, or of ss–ds transitional regions might be key to gene targeting by rAAV.
[]
Therefore, DNA repair factors or protein complexes involved in the cellular pathways of processing of ssDNA of specific DNA structures, such as ITRs, or of ss–ds transitional regions might be key to gene targeting by rAAV.
true
true
true
true
true
1,106
3
INTRODUCTION
1
19
[ "b19", "b20" ]
16,822,856
pmid-10775597|pmid-8627803|pmid-12663782|pmid-11711618|pmid-10775597
Deciphering the mechanism of rAAV gene targeting may in the future allow manipulation of potentially competing pathways in order to both enhance targeting rates and lower random integration events.
[ "19", "20" ]
197
6,774
0
false
Deciphering the mechanism of rAAV gene targeting may in the future allow manipulation of potentially competing pathways in order to both enhance targeting rates and lower random integration events.
[]
Deciphering the mechanism of rAAV gene targeting may in the future allow manipulation of potentially competing pathways in order to both enhance targeting rates and lower random integration events.
true
true
true
true
true
1,106
3
INTRODUCTION
1
19
[ "b19", "b20" ]
16,822,856
pmid-10775597|pmid-8627803|pmid-12663782|pmid-11711618|pmid-10775597
In this study we identified components of the cellular DNA repair/recombination machinery, which are essential for efficient rAAV-mediated gene targeting.
[ "19", "20" ]
154
6,775
0
false
In this study we identified components of the cellular DNA repair/recombination machinery, which are essential for efficient rAAV-mediated gene targeting.
[]
In this study we identified components of the cellular DNA repair/recombination machinery, which are essential for efficient rAAV-mediated gene targeting.
true
true
true
true
true
1,106
0
DISCUSSION
1
29
[ "b29", "b39" ]
16,822,856
pmid-1620105|pmid-11039937|pmid-10805797|pmid-15563511|pmid-15521053|pmid-9537413|pmid-12089561
Understanding the mechanisms underlying the process of rAAV-mediated gene targeting shown previously to reach unusually high frequencies (29,39) will likely be beneficial for gene therapy applications and will contribute to our knowledge of virus-host interactions and DNA dynamics.
[ "29", "39" ]
282
6,776
0
false
Understanding the mechanisms underlying the process of rAAV-mediated gene targeting shown previously to reach unusually high frequencies will likely be beneficial for gene therapy applications and will contribute to our knowledge of virus-host interactions and DNA dynamics.
[ "29,39" ]
Understanding the mechanisms underlying the process of rAAV-mediated gene targeting shown previously to reach unusually high frequencies will likely be beneficial for gene therapy applications and will contribute to our knowledge of virus-host interactions and DNA dynamics.
true
true
true
true
true
1,107
0
DISCUSSION
1
29
[ "b29", "b39" ]
16,822,856
pmid-1620105|pmid-11039937|pmid-10805797|pmid-15563511|pmid-15521053|pmid-9537413|pmid-12089561
We utilized RNA interference to examine the role of cellular proteins involved in DNA repair and recombination pathways for rAAV-mediated gene targeting.
[ "29", "39" ]
153
6,777
0
false
We utilized RNA interference to examine the role of cellular proteins involved in DNA repair and recombination pathways for rAAV-mediated gene targeting.
[]
We utilized RNA interference to examine the role of cellular proteins involved in DNA repair and recombination pathways for rAAV-mediated gene targeting.
true
true
true
true
true
1,107
0
DISCUSSION
1
29
[ "b29", "b39" ]
16,822,856
pmid-1620105|pmid-11039937|pmid-10805797|pmid-15563511|pmid-15521053|pmid-9537413|pmid-12089561
Compared with the non-silenced parent populations, all polyclonal silenced populations proliferated with the same rate and contained similar numbers of RFP positive cells indicative of infection.
[ "29", "39" ]
195
6,778
0
false
Compared with the non-silenced parent populations, all polyclonal silenced populations proliferated with the same rate and contained similar numbers of RFP positive cells indicative of infection.
[]
Compared with the non-silenced parent populations, all polyclonal silenced populations proliferated with the same rate and contained similar numbers of RFP positive cells indicative of infection.
true
true
true
true
true
1,107
0
DISCUSSION
1
29
[ "b29", "b39" ]
16,822,856
pmid-1620105|pmid-11039937|pmid-10805797|pmid-15563511|pmid-15521053|pmid-9537413|pmid-12089561
Therefore, the silencing procedure does not seem to affect parameters critical for a valid comparison of targeting rates, such as the kinetics of rAAV transduction, surface receptor expression, or growth properties of the cells.
[ "29", "39" ]
228
6,779
0
false
Therefore, the silencing procedure does not seem to affect parameters critical for a valid comparison of targeting rates, such as the kinetics of rAAV transduction, surface receptor expression, or growth properties of the cells.
[]
Therefore, the silencing procedure does not seem to affect parameters critical for a valid comparison of targeting rates, such as the kinetics of rAAV transduction, surface receptor expression, or growth properties of the cells.
true
true
true
true
true
1,107
1
DISCUSSION
1
9
[ "b9" ]
16,822,856
pmid-2725520|pmid-12109211|pmid-15932801|pmid-16261169|pmid-14732747|pmid-14704360|pmid-15950905|pmid-12833043|pmid-12778174|pmid-16261169
Several types of mutations have been efficiently corrected using rAAV vectors [reviewed in (9)].
[ "9" ]
96
6,780
0
false
Several types of mutations have been efficiently corrected using rAAV vectors.
[ "reviewed in (9)" ]
Several types of mutations have been efficiently corrected using rAAV vectors.
true
true
true
true
true
1,108
1
DISCUSSION
1
9
[ "b9" ]
16,822,856
pmid-2725520|pmid-12109211|pmid-15932801|pmid-16261169|pmid-14732747|pmid-14704360|pmid-15950905|pmid-12833043|pmid-12778174|pmid-16261169
In our system, rAAV targeting vectors achieve high fidelity correction of a 32 bp deletion at a stable, long-term targeting frequency of 0.02% consistent with previous observations made under non-selective conditions.
[ "9" ]
217
6,781
0
false
In our system, rAAV targeting vectors achieve high fidelity correction of a 32 bp deletion at a stable, long-term targeting frequency of 0.02% consistent with previous observations made under non-selective conditions.
[]
In our system, rAAV targeting vectors achieve high fidelity correction of a 32 bp deletion at a stable, long-term targeting frequency of 0.02% consistent with previous observations made under non-selective conditions.
true
true
true
true
true
1,108
1
DISCUSSION
1
9
[ "b9" ]
16,822,856
pmid-2725520|pmid-12109211|pmid-15932801|pmid-16261169|pmid-14732747|pmid-14704360|pmid-15950905|pmid-12833043|pmid-12778174|pmid-16261169
Also consistent with earlier reports, we observed significant improvement in the frequency of repair with the increase of the vector load.
[ "9" ]
138
6,782
0
false
Also consistent with earlier reports, we observed significant improvement in the frequency of repair with the increase of the vector load.
[]
Also consistent with earlier reports, we observed significant improvement in the frequency of repair with the increase of the vector load.
true
true
true
true
true
1,108
1
DISCUSSION
1
9
[ "b9" ]
16,822,856
pmid-2725520|pmid-12109211|pmid-15932801|pmid-16261169|pmid-14732747|pmid-14704360|pmid-15950905|pmid-12833043|pmid-12778174|pmid-16261169
Besides efficient delivery of vector DNA, the length of homology between vector and target proved important.
[ "9" ]
108
6,783
0
false
Besides efficient delivery of vector DNA, the length of homology between vector and target proved important.
[]
Besides efficient delivery of vector DNA, the length of homology between vector and target proved important.
true
true
true
true
true
1,108
1
DISCUSSION
1
9
[ "b9" ]
16,822,856
pmid-2725520|pmid-12109211|pmid-15932801|pmid-16261169|pmid-14732747|pmid-14704360|pmid-15950905|pmid-12833043|pmid-12778174|pmid-16261169
A 2-fold extension of the 3′ homology between the chromosomal substrate and the recombinant viral vector resulted in an increase in the repair frequency of up to 73-fold at low, 101-fold at intermediate and 23-fold at high vector dose.
[ "9" ]
235
6,784
0
false
A 2-fold extension of the 3′ homology between the chromosomal substrate and the recombinant viral vector resulted in an increase in the repair frequency of up to 73-fold at low, 101-fold at intermediate and 23-fold at high vector dose.
[]
A 2-fold extension of the 3′ homology between the chromosomal substrate and the recombinant viral vector resulted in an increase in the repair frequency of up to 73-fold at low, 101-fold at intermediate and 23-fold at high vector dose.
true
true
true
true
true
1,108
1
DISCUSSION
1
9
[ "b9" ]
16,822,856
pmid-2725520|pmid-12109211|pmid-15932801|pmid-16261169|pmid-14732747|pmid-14704360|pmid-15950905|pmid-12833043|pmid-12778174|pmid-16261169
The length of homology that can be included in the rAAV system is limited by the packaging capacity of the virus, which is about 4.7 kb, and for maximal targeting efficiency at low MOI the longest possible homology should be used.
[ "9" ]
230
6,785
0
false
The length of homology that can be included in the rAAV system is limited by the packaging capacity of the virus, which is about 4.7 kb, and for maximal targeting efficiency at low MOI the longest possible homology should be used.
[]
The length of homology that can be included in the rAAV system is limited by the packaging capacity of the virus, which is about 4.7 kb, and for maximal targeting efficiency at low MOI the longest possible homology should be used.
true
true
true
true
true
1,108
1
DISCUSSION
1
9
[ "b9" ]
16,822,856
pmid-2725520|pmid-12109211|pmid-15932801|pmid-16261169|pmid-14732747|pmid-14704360|pmid-15950905|pmid-12833043|pmid-12778174|pmid-16261169
Still, the rAAV system requires less extended homology than conventional targeting systems at mostly higher targeting frequencies.
[ "9" ]
130
6,786
0
false
Still, the rAAV system requires less extended homology than conventional targeting systems at mostly higher targeting frequencies.
[]
Still, the rAAV system requires less extended homology than conventional targeting systems at mostly higher targeting frequencies.
true
true
true
true
true
1,108
2
DISCUSSION
1
24
[ "b24", "b36", "b38", "b40" ]
16,822,856
pmid-12724414|pmid-12724413|pmid-12663782|pmid-11711618|pmid-7855602|pmid-11782437|pmid-3347204|pmid-8805304
We have tested the effect of silencing several genes that are key to NHEJ and HR, including DNA-PK, RAD54L, RAD54B or XRCC3.
[ "24", "36", "38", "40" ]
124
6,787
0
false
We have tested the effect of silencing several genes that are key to NHEJ and HR, including DNA-PK, RAD54L, RAD54B or XRCC3.
[]
We have tested the effect of silencing several genes that are key to NHEJ and HR, including DNA-PK, RAD54L, RAD54B or XRCC3.
true
true
true
true
true
1,109
2
DISCUSSION
1
24
[ "b24", "b36", "b38", "b40" ]
16,822,856
pmid-12724414|pmid-12724413|pmid-12663782|pmid-11711618|pmid-7855602|pmid-11782437|pmid-3347204|pmid-8805304
Cell lines deficient in either Rad54L or Rad54B or carrying non-functional mutants of DNA-PK and XRCC3 are viable (24,36,38,40), rendering RNA interference feasible.
[ "24", "36", "38", "40" ]
165
6,788
0
false
Cell lines deficient in either Rad54L or Rad54B or carrying non-functional mutants of DNA-PK and XRCC3 are viable, rendering RNA interference feasible.
[ "24,36,38,40" ]
Cell lines deficient in either Rad54L or Rad54B or carrying non-functional mutants of DNA-PK and XRCC3 are viable, rendering RNA interference feasible.
true
true
true
true
true
1,109
3
DISCUSSION
1
17
[ "b17", "b18", "b19" ]
16,822,856
pmid-10775597|pmid-8627803|pmid-12663782|pmid-11711618|pmid-10775597
Absence of DNA-PK reduces circularization of linear dsrAAV genomes by about 50% (17) and one member of the DNA–PK complex, KU86, apparently binds to rAAV DNA, and acts as an inhibitor of rAAV transduction (18).
[ "17", "18", "19" ]
210
6,789
1
false
Absence of DNA-PK reduces circularization of linear dsrAAV genomes by about 50% and one member of the DNA–PK complex, KU86, apparently binds to rAAV DNA, and acts as an inhibitor of rAAV transduction.
[ "17", "18" ]
Absence of DNA-PK reduces circularization of linear dsrAAV genomes by about 50% and one member of the DNA–PK complex, KU86, apparently binds to rAAV DNA, and acts as an inhibitor of rAAV transduction.
true
true
true
true
true
1,110
3
DISCUSSION
1
17
[ "b17", "b18", "b19" ]
16,822,856
pmid-10775597|pmid-8627803|pmid-12663782|pmid-11711618|pmid-10775597
In this report, we demonstrate that rAAV gene targeting does not depend on NHEJ since transcriptional silencing of DNA-PKcs does not affect targeting frequencies.
[ "17", "18", "19" ]
162
6,790
0
false
In this report, we demonstrate that rAAV gene targeting does not depend on NHEJ since transcriptional silencing of DNA-PKcs does not affect targeting frequencies.
[]
In this report, we demonstrate that rAAV gene targeting does not depend on NHEJ since transcriptional silencing of DNA-PKcs does not affect targeting frequencies.
true
true
true
true
true
1,110
3
DISCUSSION
1
19
[ "b17", "b18", "b19" ]
16,822,856
pmid-10775597|pmid-8627803|pmid-12663782|pmid-11711618|pmid-10775597
It is likely that the higher number of GFP positive cells in the DNA-PKcs silenced population observed at day 3 (Figure 3C) is due to reduced circularization and abundance of linear rAAV monomer genomes, which have been shown to be effective in targeting (19).
[ "17", "18", "19" ]
260
6,791
1
false
It is likely that the higher number of GFP positive cells in the DNA-PKcs silenced population observed at day 3 (Figure 3C) is due to reduced circularization and abundance of linear rAAV monomer genomes, which have been shown to be effective in targeting.
[ "19" ]
It is likely that the higher number of GFP positive cells in the DNA-PKcs silenced population observed at day 3 (Figure 3C) is due to reduced circularization and abundance of linear rAAV monomer genomes, which have been shown to be effective in targeting.
true
true
true
true
true
1,110
4
DISCUSSION
1
40
[ "b40", "b41", "b36", "b42" ]
16,822,856
pmid-8805304|pmid-10362364|pmid-11782437|pmid-12205100
However, we identified components of the RAD51/RAD54 pathway of HR as central to rAAV-mediated gene targeting.
[ "40", "41", "36", "42" ]
110
6,792
0
false
However, we identified components of the RAD51/RAD54 pathway of HR as central to rAAV-mediated gene targeting.
[]
However, we identified components of the RAD51/RAD54 pathway of HR as central to rAAV-mediated gene targeting.
true
true
true
true
true
1,111
4
DISCUSSION
1
40
[ "b40", "b41", "b36", "b42" ]
16,822,856
pmid-8805304|pmid-10362364|pmid-11782437|pmid-12205100
We found that reduced protein levels of the two Rad54-homologous genes in human cells, RAD54L and RAD54B result in decreased stable rAAV-mediated targeting rates by 2- and 6-fold, respectively.
[ "40", "41", "36", "42" ]
193
6,793
0
false
We found that reduced protein levels of the two Rad54-homologous genes in human cells, RAD54L and RAD54B result in decreased stable rAAV-mediated targeting rates by 2- and 6-fold, respectively.
[]
We found that reduced protein levels of the two Rad54-homologous genes in human cells, RAD54L and RAD54B result in decreased stable rAAV-mediated targeting rates by 2- and 6-fold, respectively.
true
true
true
true
true
1,111
4
DISCUSSION
1
40
[ "b40", "b41", "b36", "b42" ]
16,822,856
pmid-8805304|pmid-10362364|pmid-11782437|pmid-12205100
and RAD54B are members of the RAD52 epistasis group and belong to the SNF2/SWI2 family of proteins that dissociate and remodel protein complexes on DNA (40,41).
[ "40", "41", "36", "42" ]
160
6,794
0
false
and RAD54B are members of the RAD52 epistasis group and belong to the SNF2/SWI2 family of proteins that dissociate and remodel protein complexes on DNA.
[ "40,41" ]
and RAD54B are members of the RAD52 epistasis group and belong to the SNF2/SWI2 family of proteins that dissociate and remodel protein complexes on DNA.
false
true
true
true
false
1,111
4
DISCUSSION
1
36
[ "b40", "b41", "b36", "b42" ]
16,822,856
pmid-8805304|pmid-10362364|pmid-11782437|pmid-12205100
Our data are consistent with up to 10-fold reduced targeting frequencies in colon cancer cell lines with inactivated RAD54B (36).
[ "40", "41", "36", "42" ]
129
6,795
1
false
Our data are consistent with up to 10-fold reduced targeting frequencies in colon cancer cell lines with inactivated RAD54B.
[ "36" ]
Our data are consistent with up to 10-fold reduced targeting frequencies in colon cancer cell lines with inactivated RAD54B.
true
true
true
true
true
1,111
4
DISCUSSION
1
42
[ "b40", "b41", "b36", "b42" ]
16,822,856
pmid-8805304|pmid-10362364|pmid-11782437|pmid-12205100
RAD54L facilitates strand-exchange by RAD51, which binds to RAD54L and stimulates its ATPase activity (42).
[ "40", "41", "36", "42" ]
107
6,796
1
false
RAD54L facilitates strand-exchange by RAD51, which binds to RAD54L and stimulates its ATPase activity.
[ "42" ]
RAD54L facilitates strand-exchange by RAD51, which binds to RAD54L and stimulates its ATPase activity.
true
true
true
true
true
1,111
4
DISCUSSION
1
40
[ "b40", "b41", "b36", "b42" ]
16,822,856
pmid-8805304|pmid-10362364|pmid-11782437|pmid-12205100
Since the yeast homologue of RAD54B, TID1/RDH54 acts in the same recombinational repair pathway as RAD54L via roles partially overlapping with those of RAD54 the residual levels of targeting we observed in the absence of either protein were to be expected.
[ "40", "41", "36", "42" ]
256
6,797
0
false
Since the yeast homologue of RAD54B, TID1/RDH54 acts in the same recombinational repair pathway as RAD54L via roles partially overlapping with those of RAD54 the residual levels of targeting we observed in the absence of either protein were to be expected.
[]
Since the yeast homologue of RAD54B, TID1/RDH54 acts in the same recombinational repair pathway as RAD54L via roles partially overlapping with those of RAD54 the residual levels of targeting we observed in the absence of either protein were to be expected.
true
true
true
true
true
1,111
4
DISCUSSION
1
40
[ "b40", "b41", "b36", "b42" ]
16,822,856
pmid-8805304|pmid-10362364|pmid-11782437|pmid-12205100
Lack of reports on the viability and proliferative capacity of cells deficient in both RAD54L and RAD54B, renders the outcome of a potential double silencing experiment to test this functional redundancy in HR very uncertain.
[ "40", "41", "36", "42" ]
225
6,798
0
false
Lack of reports on the viability and proliferative capacity of cells deficient in both RAD54L and RAD54B, renders the outcome of a potential double silencing experiment to test this functional redundancy in HR very uncertain.
[]
Lack of reports on the viability and proliferative capacity of cells deficient in both RAD54L and RAD54B, renders the outcome of a potential double silencing experiment to test this functional redundancy in HR very uncertain.
true
true
true
true
true
1,111
5
DISCUSSION
1
35
[ "b35", "b43", "b44", "b38", "b44", "b45", "b46", "b47", "b48", "b49", "b45", "b50", "b51", "b52", "b53", "b54", "b55" ]
16,822,856
pmid-12456786|pmid-8943369|pmid-11025669|pmid-3347204|pmid-11025669|pmid-15372620|pmid-12191483|pmid-11751635|pmid-12718895|pmid-14716019|pmid-15372620|pmid-11459987|pmid-12228710|pmid-15703751|pmid-15037616|pmid-10880452|pmid-11356153
RAD51 plays a central role in HR by replacing RPA from single-stranded DNA and forming a nucleoprotein filament that participates in homologous pairing (35).
[ "35", "43", "44", "38", "44", "45", "46", "47", "48", "49", "45", "50", "51", "52", "53", "54", "55" ]
157
6,799
1
false
RAD51 plays a central role in HR by replacing RPA from single-stranded DNA and forming a nucleoprotein filament that participates in homologous pairing.
[ "35" ]
RAD51 plays a central role in HR by replacing RPA from single-stranded DNA and forming a nucleoprotein filament that participates in homologous pairing.
true
true
true
true
true
1,112