Mamba-SSM with LLM Reasoning for Biomarker Discovery: Causal Feature Refinement via Chain-of-Thought Gene Evaluation

Gradient saliency from deep sequence models surfaces candidate biomarkers efficiently, but the resulting gene lists are contaminated by tissue-composition confounders that degrade downstream classifiers. We study whether LLM chain-of-thought (CoT) reasoning can faithfully filter these confounders, and whether reasoning quality drives downstream performance. We train a Mamba SSM on TCGA-BRCA RNA-seq and extract the top-50 genes by gradient saliency; DeepSeek-R1 evaluates every candidate with structured CoT to produce a final 17-gene set. The raw 50-gene saliency set (no LLM) performs worse than a 5,000-gene variance baseline (AUC 0.832 vs. 0.903), while the LLM-filtered set surpasses it (AUC 0.927), using 294x fewer features. A faithfulness audit (COSMIC CGC, OncoKB, PAM50) reveals only 6 of 17 selected genes (35.3%) are validated BRCA biomarkers, yet 10 of 16 known BRCA genes in the input were missed - including FOXA1. This gap between downstream performance and reasoning faithfulness suggests selective faithfulness: targeted confounder removal is sufficient for performance gains even without comprehensive recall.

Physical Consistency of Aurora's Encoder: A Quantitative Study

The high accuracy of large-scale weather forecasting models like Aurora is often accompanied by a lack of transparency, as their internal representations remain largely opaque. This "black box" nature hinders their adoption in high-stakes operational settings. In this work, we probe the physical consistency of Aurora's encoder by investigating whether its latent representations align with known physical and meteorological concepts. Using a large-scale dataset of embeddings, we train linear classifiers to identify three distinct concepts: the fundamental land-sea boundary, high-impact extreme temperature events, and atmospheric instability. Our findings provide quantitative evidence that Aurora learns physically consistent features, while also highlighting its limitations in capturing the rarest events. This work underscores the critical need for interpretability methods to validate and build trust in the next generation of Al-driven weather models.