PertReason: A Knowledge-Grounded Benchmark and Framework for Cell-State-Conditioned Mechanistic Reasoning of Perturbation Effects

TL;DR - PertReason is a benchmark and framework for evaluating whether models explain single-cell perturbation effects with mechanisms grounded in cell-specific states. It exposes failures that predictive accuracy alone misses, including correct answers derived from flawed or context-insensitive reasoning.

• PertReasonQA combines genetic and chemical perturbation data across cellular contexts with knowledge graphs.
• Dynamic pathway conditioning tests robustness to unseen perturbations, new cells, and differing basal states.
• Evaluated models sometimes ignore cellular context or produce directionally inconsistent mechanisms.
• PertReasonLM aligns outcome predictions with context-specific, pathway-grounded rationales as a reference approach.