ReDisX: a Continuous Max Flow-based framework to redefine the diagnosis of diseases based on identified patterns of genomic signatures

Author:

Yip Hiu FungORCID,Chowdhury DebajyotiORCID,Wang Kexin,Liu Yujie,Gao Yao,Lan Liang,Zheng Chaochao,Guan Daogang,Lam Kei Fong,Zhu Hailong,Tai Xuecheng,Lu Aiping

Abstract

AbstractDiseases originate at the molecular-genetic layer, manifest through altered biochemical homeostasis, and develop symptoms later. Hence symptomatic diagnosis is inadequate to explain the underlying molecular-genetic abnormality and individual genomic disparities. The current trends include molecular-genetic information relying on algorithms to recognize the disease subtypes through gene expressions. Despite their disposition toward disease-specific heterogeneity and cross-disease homogeneity, a gap still exists to describe the extent of homogeneity within the heterogeneous subpopulation of different diseases. They are limited to obtaining the holistic sense of the whole genome-based diagnosis resulting in inaccurate diagnosis and subsequent management.To fill those gaps, we proposed ReDisX framework, a scalable machine learning algorithm that uniquely classifies patients based on their genomic signatures. It was deployed to re-categorizes the patients with rheumatoid arthritis and coronary artery disease. It reveals heterogeneous subpopulations within a disease and homogenous subpopulations across different diseases. Besides, it identifies GZMB as a subpopulation-differentiation marker that plausibly serves as a prominent indicator for GZMB-targeted drug repurposing.The ReDisX framework offers a novel strategy to redefine disease diagnosis through characterizing personalized genomic signatures. It may rejuvenate the landscape of precision and personalized diagnosis, and a clue to drug repurposing.

Publisher

Cold Spring Harbor Laboratory

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