Variational and Explanatory Neural Networks for Encoding Cancer Profiles and Predicting Drug Responses

TL;DR

This paper introduces VETE, a neural network framework that improves cancer transcriptomics data encoding by reducing noise and providing biological interpretability, leading to better prediction of drug responses and understanding of underlying mechanisms.

Contribution

VETE combines a variational approach with traceable gene ontology integration, offering both accurate predictions and biological explanations in cancer research.

Findings

VETE achieves robust accuracy in cancer cell line classification.

It effectively predicts anti-cancer drug responses.

Provides biological insights into drug response mechanisms.

Abstract

Human cancers present a significant public health challenge and require the discovery of novel drugs through translational research. Transcriptomics profiling data that describes molecular activities in tumors and cancer cell lines are widely utilized for predicting anti-cancer drug responses. However, existing AI models face challenges due to noise in transcriptomics data and lack of biological interpretability. To overcome these limitations, we introduce VETE (Variational and Explanatory Transcriptomics Encoder), a novel neural network framework that incorporates a variational component to mitigate noise effects and integrates traceable gene ontology into the neural network architecture for encoding cancer transcriptomics data. Key innovations include a local interpretability-guided method for identifying ontology paths, a visualization tool to elucidate biological mechanisms of drug responses, and the application of centralized large scale hyperparameter optimization. VETE demonstrated robust accuracy in cancer cell line classification and drug response prediction. Additionally, it provided traceable biological explanations for both tasks and offers insights into the mechanisms underlying its predictions. VETE bridges the gap between AI-driven predictions and biologically meaningful insights in cancer research, which represents a promising advancement in the field.