Understanding Breast Cancer Survival: Using Causality and Language Models on Multi-omics Data

TL;DR

This paper explores the use of causal discovery algorithms combined with large language models to identify and validate factors affecting breast cancer survival from multi-omics data, aiming for more explainable clinical insights.

Contribution

It introduces a novel approach integrating causal discovery methods with language models to evaluate causal relations in breast cancer prognosis from genomic data.

Findings

Identified key causal factors related to patient survival.

Validated causal findings using biomedical language models.

Highlighted the potential and challenges of causal discovery in healthcare.

Abstract

The need for more usable and explainable machine learning models in healthcare increases the importance of developing and utilizing causal discovery algorithms, which aim to discover causal relations by analyzing observational data. Explainable approaches aid clinicians and biologists in predicting the prognosis of diseases and suggesting proper treatments. However, very little research has been conducted at the crossroads between causal discovery, genomics, and breast cancer, and we aim to bridge this gap. Moreover, evaluation of causal discovery methods on real data is in general notoriously difficult because ground-truth causal relations are usually unknown, and accordingly, in this paper, we also propose to address the evaluation problem with large language models. In particular, we exploit suitable causal discovery algorithms to investigate how various perturbations in the genome can affect the survival of patients diagnosed with breast cancer. We used three main causal discovery algorithms: PC, Greedy Equivalence Search (GES), and a Generalized Precision Matrix-based one. We experiment with a subset of The Cancer Genome Atlas, which contains information about mutations, copy number variations, protein levels, and gene expressions for 705 breast cancer patients. Our findings reveal important factors related to the vital status of patients using causal discovery algorithms. However, the reliability of these results remains a concern in the medical domain. Accordingly, as another contribution of the work, the results are validated through language models trained on biomedical literature, such as BlueBERT and other large language models trained on medical corpora. Our results profess proper utilization of causal discovery algorithms and language models for revealing reliable causal relations for clinical applications.