Deep Learning-Based, Multiclass Approach to Cancer Classification on Liquid Biopsy Data
Maksym A. Jopek, Krzysztof Pastuszak, Sebastian Cygert, Myron G. Best, Thomas Würdinger, Jacek Jassem, Anna J. Żaczek, Anna Supernat
Abstract
<italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Objective</i> : The field of cancer diagnostics has been revolutionized by liquid biopsies, which offer a bridge between laboratory research and clinical settings. These tests are less invasive than traditional biopsies and more convenient than routine imaging methods. Liquid biopsies allow studying of tumor-derived markers in bodily fluids, enabling the development of more precise cancer diagnostic tests for screening, disease monitoring, and therapy personalization. This study presents a multiclass approach based on deep learning to analyze and classify diseases based on blood platelet RNA. Its primary objective is to enhance cancer-type diagnosis in clinical settings by leveraging the power of deep learning combined with high-throughput sequencing of liquid biopsy. Ultimately, the study demonstrates the potential of this approach to accurately identify the patient’s type of cancer. <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Methods</i> : The developed method classifies patients using heatmap images, generated based on gene expression arranged according to the Kyoto Encyclopedia of Genes and Genomes pathways. The images represent samples of patients with ovarian cancer, endometrial cancer, glioblastoma, non-small cell lung cancer, and sarcoma, as well as cancer patients with brain metastasis. <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Results</i> : Our deep learning-based models reached 66.51% balanced accuracy when distinguishing between those 6 sites of cancer origin and 90.5% balanced accuracy on a location-specific dataset where cancer types from close locations were grouped. The developed models were further investigated with an explainable artificial intelligence-based approach (XAI) -SHAP. They returned a set of 60 genes with the highest impact on the models’ decision-making process. <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Conclusions</i> : Our results show that deep-learning methods are a promising opportunity for cancer detection and could support clinicians’ decision-making process in finding the solution for the black-box problem.