Woo Youn Kim

Yinhua Piao, Hyomin Kim, Seonghwan Kim et al.

Predicting high-dimensional transcriptional responses to genetic perturbations is challenging because signals are sparse and experimental noise is severe. Existing methods often suffer from mean collapse, achieving high correlation by predicting the global average expression rather than perturbation-specific responses, which yields false positives and poor interpretability. Methods that add biological knowledge graphs typically treat them as dense, static priors shared across perturbations, propagating noise. We propose AdaPert, which counters mean collapse by extracting a sparse, perturbation-specific subgraph via differentiable node selection, then suppressing spurious variation in non-responsive genes while emphasizing differentially expressed ones. Across multiple benchmarks, \textsc{AdaPert} outperforms existing baselines, with the largest gains on DEG-aware metrics.

Hyomin Kim, Sang-Yeon Hwang, Jaechang Lim et al.

Predicting gene regulation responses to biological perturbations requires reasoning about underlying biological causalities. While large language models (LLMs) show promise for such tasks, they are often overwhelmed by the entangled nature of high-dimensional perturbation results. Moreover, recent works have primarily focused on genetic perturbations in single-cell experiments, leaving bulk-cell chemical perturbations, which is central to drug discovery, largely unexplored. Motivated by this, we present LINCSQA, a novel benchmark for predicting target gene regulation under complex chemical perturbations in bulk-cell environments. We further propose PBio-Agent, a multi-agent framework that integrates difficulty-aware task sequencing with iterative knowledge refinement. Our key insight is that genes affected by the same perturbation share causal structure, allowing confidently predicted genes to contextualize more challenging cases. The framework employs specialized agents enriched with biological knowledge graphs, while a synthesis agent integrates outputs and specialized judges ensure logical coherence. PBio-Agent outperforms existing baselines on both LINCSQA and PerturbQA, enabling even smaller models to predict and explain complex biological processes without additional training.