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ABSTRACT: Motivation
Human diseases are characterized by multiple features such as their pathophysiological, molecular and genetic changes. The rapid expansion of such multi-modal disease-omics space provides an opportunity to re-classify diverse human diseases and to uncover their latent molecular similarities, which could be exploited to repurpose a therapeutic-target for one disease to another. Results
Herein, we probe this underexplored space by soft-clustering 6955 human diseases by multi-modal generative topic modeling. Focusing on chronic kidney disease and myocardial infarction, two most life-threatening diseases, unveiled are their previously underrecognized molecular similarities to neoplasia and mental/neurological-disorders, and 69 repurposable therapeutic-targets for these diseases. Using an edit-distance-based pathway-classifier, we also find molecular pathways by which these targets could elicit their clinical effects. Importantly, for the 17 targets, the evidence for their therapeutic usefulness is retrospectively found in the pre-clinical and clinical space, illustrating the effectiveness of the method, and suggesting its broader applications across diverse human diseases. Availability and implementation
The code reported in this article is available at: https://github.com/skozawa170301ktx/MultiModalDiseaseModeling Supplementary information
Supplementary data are available at Bioinformatics Advances online.
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PROVIDER: S-EPMC10133403 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature