FusionNW, a potential clinical impact assessment of kinases in pan-cancer fusion gene network

Author:

Yang Chengyuan1,Kumar Himansu2ORCID,Kim Pora2ORCID

Affiliation:

1. School of Public Health, The University of Texas Health Science Center at Houston , Houston, TX 77030 , USA

2. McWilliams School of Biomedical Informatics, The University of Texas Health Science Center at Houston , Houston, TX 77030 , USA

Abstract

Abstract Kinase fusion genes are the most active fusion gene group in human cancer fusion genes. To help choose the clinically significant kinase so that the cancer patients that have fusion genes can be better diagnosed, we need a metric to infer the assessment of kinases in pan-cancer fusion genes rather than relying on the sample frequency expressed fusion genes. Most of all, multiple studies assessed human kinases as the drug targets using multiple types of genomic and clinical information, but none used the kinase fusion genes in their study. The assessment studies of kinase without kinase fusion gene events can miss the effect of one of the mechanisms that enhance the kinase function in cancer. To fill this gap, in this study, we suggest a novel way of assessing genes using a network propagation approach to infer how likely individual kinases influence the kinase fusion gene network composed of ~5K kinase fusion gene pairs. To select a better seed of propagation, we chose the top genes via dimensionality reduction like a principal component or latent layer information of six features of individual genes in pan-cancer fusion genes. Our approach may provide a novel way to assess of human kinases in cancer.

Funder

National Institutes of Health

University of Texas Health Science Center at Houston

Publisher

Oxford University Press (OUP)

Reference23 articles.

1. FusionGDB 2.0: fusion gene annotation updates aided by deep learning;Kim;Nucleic Acids Res,2022

2. Kinase impact assessment in the landscape of fusion genes that retain kinase domains: a pan-cancer study;Kim;Brief Bioinform,2018

3. Domain retention in transcription factor fusion genes and its biological and clinical implications: a pan-cancer study;Kim;Oncotarget,2017

4. Variant to function mapping at single-cell resolution through network propagation;Yu;Nat Biotechnol,2022

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