ARGUS is an evidence‑constrained framework that separates deterministic biological computation from large‑language‑model reasoning to interpret single nucleotide variants in noncoding regulatory regions. It uses 458 DNABERT‑based transcription factor binding models within a hypothesis‑directed loop where a planner selects evidence sources, a verifier interprets observations, and the investigation path adapts to uncertainty. In a case study of variant rs6983267, ARGUS generated divergent investigative trajectories for four transcription factors, demonstrating how real experimental data from ADASTRA, JASPAR, and ENCODE cCRE guide conclusions and how the LLM planner can reduce unnecessary tool calls.
arXiv:2608. 05359v1 Announce Type: new Abstract: CASCADE is an agentic framework that predicts downstream transcriptional effects of gene perturbation from precomputed ARACNe regulatory networks, exposed via MCP.
The study evaluates whether biological reasoning models actually use their biological inputs by testing six models on DNA, protein, and single‑cell tasks. By perturbing one biological input while keeping others fixed, the authors find that many models (e.g., Evo2, ESM3, BioReason, BioReason‑Pro) rely primarily on textual information, with minimal impact from the biological representations. In contrast, models like ChatNT, Prot2Text‑V2, CellWhisperer, and Cell2Sentence‑Scale show greater dependence on their biological inputs, yet overall accuracy gains do not consistently reflect increased biological input contribution.
The paper introduces ClinGeX, a large‑language‑model agent that uses 105 curated executable skills to automate clinical genomic analysis. In benchmark tests, ClinGeX achieved 71.7% macro‑averaged task‑level concordance, outperforming the best comparator at 45.7%. Human‑AI collaboration studies showed ClinGeX significantly improved case‑level concordance across variant analysis, rare disease interpretation, and oncology decision‑making, while also reducing interpretation time.
arXiv:2606. 01042v1 Announce Type: cross Abstract: Perturbation experiments are central to understanding cellular mechanisms, but remain costly and sparse, motivating prediction of gene expression responses for unobserved conditions.
arXiv:2610.24806v1 Announce Type: cross Abstract: Despite breakthroughs in AI-driven molecular generation, existing discovery pipelines operate largely in silico, with wet-lab feedback reserved for v...
The paper introduces EDB-Bio, a benchmark of 96,000 episodes drawn from real biological studies—drug‑perturbation transcriptomics, CRISPR screens, and GWAS—to test whether language models can weigh empirical evidence and predict hypothesis truth. Initial results show that both open‑weight and frontier models are systematically underconfident, matching a trivial base‑rate forecaster in Brier score, but post‑training with proper scoring rules improves calibration and discrimination. In a downstream experiment‑selection task, a calibrated model (Ibis0) outperforms the best frontier model by 2.5×, and Bayes‑factor analysis reveals how models update beliefs, align with expert relevance judgments, and expose biases.
arXiv:2604. 11305v3 Announce Type: replace Abstract: Conformal selection (CS) uses calibration data to identify test inputs whose unobserved outcomes are likely to satisfy a pre-specified minimal quality requirement, while controlling the false discovery rate (FDR).
arXiv:2606. 07607v1 Announce Type: new Abstract: Advances in machine learning and computational power have unlocked the predictive potential of the human genome, yet biologists now demand that these models also elucidate the underlying biological mechanisms.
The study evaluates whether a portfolio of compact, semantically named descriptor blocks can match the performance of a 2048‑dimensional CheMeleon embedding in low‑data molecular assays. Using a fixed 11‑dimensional physicochemical base and greedily adding provenance‑screened blocks, the portfolio achieves a mean test AUC of 0.762 across nine ADME/Tox assays, comparable to CheMeleon’s 0.764 and better than Mordred’s 0.756. The results meet a predeclared pooled parity threshold but not all per‑assay thresholds, and further analysis confirms the competitiveness of the auditable representation while highlighting unresolved assay‑level differences.
arXiv:2609.21859v1 Announce Type: new Abstract: Nearly 90% of drugs entering clinical development ultimately fail, despite billions of dollars in investment. Pharmaceutical companies therefore rely o...
arXiv:2607. 19618v1 Announce Type: cross Abstract: Genomic language models achieve strong performance across regulatory-genomics tasks, yet what these models internally represent remains opaque, and the field lacks a principled procedure for verifying that an apparent ``concept'' inside a model is real rather than an artifact of sequence composition.
arXiv:2511. 09026v2 Announce Type: replace-cross Abstract: Whole-genome sequencing (WGS) has revealed numerous non-coding short variants whose functional impacts remain poorly understood.