<b>Zero-Leakage Parquet Datasets and In Silico CRISPR Results for Colorectal Cancer 5-FU Response</b>

Engineering notes

While deep learning achieves predictive accuracy, it frequently fails to provide the mechanistic clarity required for clinical adoption.

Chinese explanation / 中文解读

中文解读待补充：本站会优先为端到端自动驾驶、BEV感知、3D目标检测、轨迹预测、路径规划、LiDAR感知等高价值论文补充中文说明。

Original abstract

Precision oncology is currently limited by the small-N, large-P paradox, where high-dimensional genomic data is abundant but pharmacological response samples are sparse. While deep learning achieves predictive accuracy, it frequently fails to provide the mechanistic clarity required for clinical adoption. We present the Contextual Invertible World Model (CIWM), a Neuro-Symbolic Agentic Framework that bridges this gap by integrating a quantitative machine learning emulator with a Large Language Model reasoning layer. Utilising a stringently curated, high-fidelity data engineering pipeline on the Sanger GDSC dataset (N = 83), we isolate true biological signals from in vitro artifacts to establish a rigorous baseline predictive correlation for complex transcriptomics (r = 0.268). Through Inverse Reasoning, we perform in silico CRISPR perturbations across the colorectal landscape. The framework autonomously overturns classical mechanistic assumptions, identifying a hierarchical dominance of mutant KRAS over the APC/Wnt-axis in driving 5-fluorouracil resistance (Δ= -0.0469) via a "KRAS Shield" mapped to MAPK/PI3K networks.Furthermore, the agentic layer identified a "PIK3CA Paradox", revealing that repairing PIK3CA inadvertently increases chemoresistance (Δ = +0.0085) by triggering a compensatory feedback loop that hyperactivates the dominant MAPK survival pathway.

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