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Jun 30

GRIMM: Genetic stRatification for Inference in Molecular Modeling

The vast majority of biological sequences encode unknown functions and bear little resemblance to experimentally characterized proteins, limiting both our understanding of biology and our ability to harness functional potential for the bioeconomy. Predicting enzyme function from sequence remains a central challenge in computational biology, complicated by low sequence diversity and imbalanced label support in publicly available datasets. Models trained on these data can overestimate performance and fail to generalize. To address this, we introduce GRIMM (Genetic stRatification for Inference in Molecular Modeling), a benchmark for enzyme function prediction that employs genetic stratification: sequences are clustered by similarity and clusters are assigned exclusively to training, validation, or test sets. This ensures that sequences from the same cluster do not appear in multiple partitions. GRIMM produces multiple test sets: a closed-set test with the same label distribution as training (Test-1) and an open-set test containing novel labels (Test-2), serving as a realistic out-of-distribution proxy for discovering novel enzyme functions. While demonstrated on enzymes, this approach is generalizable to any sequence-based classification task where inputs can be clustered by similarity. By formalizing a splitting strategy often used implicitly, GRIMM provides a unified and reproducible framework for closed- and open-set evaluation. The method is lightweight, requiring only sequence clustering and label annotations, and can be adapted to different similarity thresholds, data scales, and biological tasks. GRIMM enables more realistic evaluation of functional prediction models on both familiar and unseen classes and establishes a benchmark that more faithfully assesses model performance and generalizability.

  • 2 authors
·
Feb 17

Towards Distribution-Agnostic Generalized Category Discovery

Data imbalance and open-ended distribution are two intrinsic characteristics of the real visual world. Though encouraging progress has been made in tackling each challenge separately, few works dedicated to combining them towards real-world scenarios. While several previous works have focused on classifying close-set samples and detecting open-set samples during testing, it's still essential to be able to classify unknown subjects as human beings. In this paper, we formally define a more realistic task as distribution-agnostic generalized category discovery (DA-GCD): generating fine-grained predictions for both close- and open-set classes in a long-tailed open-world setting. To tackle the challenging problem, we propose a Self-Balanced Co-Advice contrastive framework (BaCon), which consists of a contrastive-learning branch and a pseudo-labeling branch, working collaboratively to provide interactive supervision to resolve the DA-GCD task. In particular, the contrastive-learning branch provides reliable distribution estimation to regularize the predictions of the pseudo-labeling branch, which in turn guides contrastive learning through self-balanced knowledge transfer and a proposed novel contrastive loss. We compare BaCon with state-of-the-art methods from two closely related fields: imbalanced semi-supervised learning and generalized category discovery. The effectiveness of BaCon is demonstrated with superior performance over all baselines and comprehensive analysis across various datasets. Our code is publicly available.

  • 10 authors
·
Oct 2, 2023

IOMatch: Simplifying Open-Set Semi-Supervised Learning with Joint Inliers and Outliers Utilization

Semi-supervised learning (SSL) aims to leverage massive unlabeled data when labels are expensive to obtain. Unfortunately, in many real-world applications, the collected unlabeled data will inevitably contain unseen-class outliers not belonging to any of the labeled classes. To deal with the challenging open-set SSL task, the mainstream methods tend to first detect outliers and then filter them out. However, we observe a surprising fact that such approach could result in more severe performance degradation when labels are extremely scarce, as the unreliable outlier detector may wrongly exclude a considerable portion of valuable inliers. To tackle with this issue, we introduce a novel open-set SSL framework, IOMatch, which can jointly utilize inliers and outliers, even when it is difficult to distinguish exactly between them. Specifically, we propose to employ a multi-binary classifier in combination with the standard closed-set classifier for producing unified open-set classification targets, which regard all outliers as a single new class. By adopting these targets as open-set pseudo-labels, we optimize an open-set classifier with all unlabeled samples including both inliers and outliers. Extensive experiments have shown that IOMatch significantly outperforms the baseline methods across different benchmark datasets and different settings despite its remarkable simplicity. Our code and models are available at https://github.com/nukezil/IOMatch.

  • 4 authors
·
Aug 25, 2023

Fully Open Meditron: An Auditable Pipeline for Clinical LLMs

Clinical decision support systems (CDSS) require scrutable, auditable pipelines that enable rigorous, reproducible validation. Yet current LLM-based CDSS remain largely opaque. Most "open" models are open-weight only, releasing parameters while withholding the data provenance, curation procedures, and generation pipelines that determine model behavior. Fully Open (FO) models, which expose the complete training stack end-to-end, do not currently exist in medicine. We introduce Fully Open Meditron, the first fully open pipeline for building LLM-CDSS, comprising a clinician-audited training corpus, a reproducible data construction and training framework, and a use-aligned evaluation protocol. The corpus unifies eight public medical QA datasets into a normalized conversational format and expands coverage with three clinician-vetted synthetic extensions: exam-style QA, guideline-grounded QA derived from 46,469 clinical practice guidelines, and clinical vignettes. The pipeline enforces system-wide decontamination, gold-label resampling of teacher generations, and end-to-end validation by a four-physician panel. We evaluate using an LLM-as-a-judge protocol over expert-written clinical vignettes, calibrated against 204 human raters. We apply the recipe to five FO base models (Apertus-70B/8B-Instruct, OLMo-2-32B-SFT, EuroLLM-22B/9B-Instruct). All MeditronFO variants are preferred over their bases. Apertus-70B-MeditronFO improves +6.6 points over its base (47.2% to 53.8%) on aggregate medical benchmarks, establishing a new FO SoTA. Gemma-3-27B-MeditronFO is preferred over MedGemma in 58.6% of LLM-as-a-judge comparisons and outperforms it on HealthBench (58% vs 55.9%). These results show that fully open pipelines can achieve state-of-the-art domain-specific performance without sacrificing auditability or reproducibility.

  • 8 authors
·
May 14

daVinci-LLM:Towards the Science of Pretraining

The foundational pretraining phase determines a model's capability ceiling, as post-training struggles to overcome capability foundations established during pretraining, yet it remains critically under-explored. This stems from a structural paradox: organizations with computational resources operate under commercial pressures that inhibit transparent disclosure, while academic institutions possess research freedom but lack pretraining-scale computational resources. daVinci-LLM occupies this unexplored intersection, combining industrial-scale resources with full research freedom to advance the science of pretraining. We adopt a fully-open paradigm that treats openness as scientific methodology, releasing complete data processing pipelines, full training processes, and systematic exploration results. Recognizing that the field lacks systematic methodology for data processing, we employ the Data Darwinism framework, a principled L0-L9 taxonomy from filtering to synthesis. We train a 3B-parameter model from random initialization across 8T tokens using a two-stage adaptive curriculum that progressively shifts from foundational capabilities to reasoning-intensive enhancement. Through 200+ controlled ablations, we establish that: processing depth systematically enhances capabilities, establishing it as a critical dimension alongside volume scaling; different domains exhibit distinct saturation dynamics, necessitating adaptive strategies from proportion adjustments to format shifts; compositional balance enables targeted intensification while preventing performance collapse; how evaluation protocol choices shape our understanding of pretraining progress. By releasing the complete exploration process, we enable the community to build upon our findings and systematic methodologies to form accumulative scientific knowledge in pretraining.

SII-GAIR-NLP SII-GAIR
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Mar 28 2