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Cho-Jui Hsieh

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Open access Jul 2026

Synthesizing Mechanistic Hypotheses from Single-Cell Omics via Discretized Feature Attribution and Empirical Language Model Grounding

Single-cell multimodal omics offer unprecedented resolution of cellular networks, yet translating continuous computational attributions into structured, testable biological mechanisms remains a persistent bottleneck. To address this limitation, we introduce an analytical pipeline employing decision trees to discretize continuous neural network attributions into explicit regulatory thresholds. These boundaries then structurally constrain large language models, enabling them to integrate established literature with empirical data to synthesize context-specific hypotheses. Applying this continuous-to-discrete framework across sparse datasets yielded novel biological mechanisms. Specifically, the framework articulated a cytoskeletal gating hierarchy governing EGF-stimulated pathways, identified transcriptomic drivers of input resistance in cortical interneurons, and delineated translational logic predicting Ki-67 abundance within spatial transcriptomics. Retrospective benchmarking validated the framework’s capacity to autonomously reconstruct published regulatory logic. Supported by a locally deployable open-weight language model and a code-free interface, this approach establishes an auditable methodology to extract robust experimental hypotheses from high-dimensional single-cell data.

J. Chen, Yunqi Hong, Alexandra Bermudez et al. · 0 citations
Jun 2026

Arena-T2I Hard: Benchmarking and Improving Faithfulness with Dependency-Aware Checklist

Faithfulness -- how precisely a generated image aligns with its prompt -- is increasingly central to the real-world utility of text-to-image (T2I) models. Existing faithfulness benchmarks, however, rely on simple atomic instructions, on which top-tier systems already achieve near-perfect scores. As T2I models enter creative workflows, users issue multi-faceted requests combining intricate spatial relationships, stylistic constraints, and complex text rendering. In this setting, a single binary VLM-judge score no longer captures which specific constraints the model fails to satisfy. We introduce Arena-T2I Hard, a 310-prompt stress benchmark drawn from real arena T2I logs, with approximately 30 decomposed yes/no constraints per prompt spanning six categories, including text rendering. The strongest closed-source system we evaluate reaches 0.855 with a 33~pp performance gap across 11 systems, demonstrating substantial discriminative power. Moreover, high public-arena rankings fail to predict faithfulness, confirming that holistic Bradley-Terry (BT) preference scores prioritize aesthetics over fine-grained prompt adherence. We propose a dependency-aware checklist reward that decomposes each prompt into a DAG of yes/no questions and zeroes descendants of failed parents, turning faithfulness into a per-constraint training signal. Combined with a BT aesthetic reward via group-decoupled normalization (GDPO), which standardizes each reward within its rollout group so neither collapses, the recipe attains a strictly better faithfulness-aesthetics trade-off on SD3.5-Medium and FLUX.1-dev under MMRB2 pairwise comparisons than every single-reward, naive weighted-sum, or 4-reward BT-ensemble baseline.

Yuanhao Ban, Tong Xie, Sohyun An et al. · 0 citations