Nhan L. Tran

Lingchao Mao, Hairong Wang, Leland S. Hu et al.

Cancer remains one of the most challenging diseases to treat in the medical field. Machine learning has enabled in-depth analysis of rich multi-omics profiles and medical imaging for cancer diagnosis and prognosis. Despite these advancements, machine learning models face challenges stemming from limited labeled sample sizes, the intricate interplay of high-dimensionality data types, the inherent heterogeneity observed among patients and within tumors, and concerns about interpretability and consistency with existing biomedical knowledge. One approach to surmount these challenges is to integrate biomedical knowledge into data-driven models, which has proven potential to improve the accuracy, robustness, and interpretability of model results. Here, we review the state-of-the-art machine learning studies that adopted the fusion of biomedical knowledge and data, termed knowledge-informed machine learning, for cancer diagnosis and prognosis. Emphasizing the properties inherent in four primary data types including clinical, imaging, molecular, and treatment data, we highlight modeling considerations relevant to these contexts. We provide an overview of diverse forms of knowledge representation and current strategies of knowledge integration into machine learning pipelines with concrete examples. We conclude the review article by discussing future directions to advance cancer research through knowledge-informed machine learning.

Lujia Wang, Hairong Wang, Fulvio D'Angelo et al.

Glioblastoma (GBM) is one of the most aggressive and lethal human cancers. Intra-tumoral genetic heterogeneity poses a significant challenge for treatment. Biopsy is invasive, which motivates the development of non-invasive, MRI-based machine learning (ML) models to quantify intra-tumoral genetic heterogeneity for each patient. This capability holds great promise for enabling better therapeutic selection to improve patient outcomes. We proposed a novel Weakly Supervised Ordinal Support Vector Machine (WSO-SVM) to predict regional genetic alteration status within each GBM tumor using MRI. WSO-SVM was applied to a unique dataset of 318 image-localized biopsies with spatially matched multiparametric MRI from 74 GBM patients. The model was trained to predict the regional genetic alteration of three GBM driver genes (EGFR, PDGFRA, and PTEN) based on features extracted from the corresponding region of five MRI contrast images. For comparison, a variety of existing ML algorithms were also applied. The classification accuracy of each gene was compared between the different algorithms. The SHapley Additive exPlanations (SHAP) method was further applied to compute contribution scores of different contrast images. Finally, the trained WSO-SVM was used to generate prediction maps within the tumoral area of each patient to help visualize the intra-tumoral genetic heterogeneity. This study demonstrated the feasibility of using MRI and WSO-SVM to enable non-invasive prediction of intra-tumoral regional genetic alteration for each GBM patient, which can inform future adaptive therapies for individualized oncology.