Predicting Genetic Mutation from Whole Slide Images via Biomedical-Linguistic Knowledge Enhanced Multi-label Classification

Predicting genetic mutations from whole slide images is indispensable for cancer diagnosis. However, existing work training multiple binary classification models faces two challenges: (a) Training multiple binary classifiers is inefficient and would inevitably lead to a class imbalance problem. (b) The biological relationships among genes are overlooked, which limits the prediction performance. To tackle these challenges, we innovatively design a Biological-knowledge enhanced PathGenomic multi-label Transformer to improve genetic mutation prediction performances. BPGT first establishes a novel gene encoder that constructs gene priors by two carefully designed modules: (a) A gene graph whose node features are the genes' linguistic descriptions and the cancer phenotype, with edges modeled by genes' pathway associations and mutation consistencies. (b) A knowledge association module that fuses linguistic and biomedical knowledge into gene priors by transformer-based graph representation learning, capturing the intrinsic relationships between different genes' mutations. BPGT then designs a label decoder that finally performs genetic mutation prediction by two tailored modules: (a) A modality fusion module that firstly fuses the gene priors with critical regions in WSIs and obtains gene-wise mutation logits. (b) A comparative multi-label loss that emphasizes the inherent comparisons among mutation status to enhance the discrimination capabilities. Sufficient experiments on The Cancer Genome Atlas benchmark demonstrate that BPGT outperforms the state-of-the-art.