arXiv Machine Learning

Do Perturbation Predictors Learn Gene Interactions? Diagnosing Extrapolation in Agentic Screening

arXiv Machine Learning
Sep 24

Discover, Falsify, Revise: Auditing Input-Use Claims from Source Code to Predictive Contribution in Agent-Discovered Cell Models

The paper introduces CELLAUDIT, a method for auditing whether inputs claimed to influence predictive models actually do so. By testing if an input can enter the computation, whether predictions depend on it, and if that dependence improves observed responses, the authors evaluate agent-generated predictors on a morphology‑transcriptomics benchmark (BBBC047). Their findings show that many models claim compound contributions that are not supported by the data, and that falsification‑guided revisions can recover genuine input effects while improving performance.

By Mengran Li, Bo Li, Chengyang Zhang, Yang Yan, Jinfeng Xu, Zhenchao Tang
arXiv Machine Learning
Sep 22

Tool-Augmented On-Policy Distillation for LLM Domain Adaptation in Sequence-Based Omics Tasks

The paper introduces OmicsBench, a new reasoning benchmark for multi‑omics sequences that includes 1,160 expert‑validated questions across DNA regulation, RNA processing, and protein function tasks, requiring traceable evidence chains. Evaluation of 17 large language models shows that scientific LLMs, while more accurate in classification, often lack valid evidence, suggesting shortcut learning. To address this, the authors propose tool‑augmented on‑policy distillation (TA‑OPD), a post‑training method that improves both evidence grounding and predictive performance across five Qwen3.5 models of varying sizes.

By Jie Ying, Zhefan Wang, Zihong Chen, Zhengqing Li, Jinzhe Li, Gang Li, Jian Liu, Fang Hu, Tao Luo, Zhonghang Yuan, Wanli Ouyang, Stan Z. Li, Fan Yang, Nanqing Dong
arXiv Statistics ML
Oct 12

Robust Machine Learning for Regulatory Sequence Modeling under Biological and Technical Distribution Shifts

The study evaluates the robustness of deep learning models for DNA regulatory sequence prediction under biologically and technically induced distribution shifts. Using a mechanistic simulation benchmark and a massively parallel reporter assay dataset, the authors show that while models perform well under mild GC content changes, they exhibit higher error, miscalibration, and coverage collapse when faced with motif rewiring, noise, and batch effects. Incorporating biological priors and uncertainty-aware selective prediction improves robustness, though protection against strong assay noise remains limited.

By Yiyao Yang