Prioritizing and characterizing functionally relevant genes across human tissues.

Knowledge of genes that are critical to a tissue's function remains difficult to ascertain and presents a major bottleneck toward a mechanistic understanding of genotype-phenotype links. Here, we present the first machine learning model-FUGUE-combining transcriptional and network features, to p...

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Autores principales:	Gowthami Somepalli, Sarthak Sahoo, Arashdeep Singh, Sridhar Hannenhalli
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/ec34913d83af4be5b41ab61cfb9daf94
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spelling	oai:doaj.org-article:ec34913d83af4be5b41ab61cfb9daf942021-12-02T19:57:24ZPrioritizing and characterizing functionally relevant genes across human tissues.1553-734X1553-735810.1371/journal.pcbi.1009194https://doaj.org/article/ec34913d83af4be5b41ab61cfb9daf942021-07-01T00:00:00Zhttps://doi.org/10.1371/journal.pcbi.1009194https://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Knowledge of genes that are critical to a tissue's function remains difficult to ascertain and presents a major bottleneck toward a mechanistic understanding of genotype-phenotype links. Here, we present the first machine learning model-FUGUE-combining transcriptional and network features, to predict tissue-relevant genes across 30 human tissues. FUGUE achieves an average cross-validation auROC of 0.86 and auPRC of 0.50 (expected 0.09). In independent datasets, FUGUE accurately distinguishes tissue or cell type-specific genes, significantly outperforming the conventional metric based on tissue-specific expression alone. Comparison of tissue-relevant transcription factors across tissue recapitulate their developmental relationships. Interestingly, the tissue-relevant genes cluster on the genome within topologically associated domains and furthermore, are highly enriched for differentially expressed genes in the corresponding cancer type. We provide the prioritized gene lists in 30 human tissues and an open-source software to prioritize genes in a novel context given multi-sample transcriptomic data.Gowthami SomepalliSarthak SahooArashdeep SinghSridhar HannenhalliPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 17, Iss 7, p e1009194 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Gowthami Somepalli Sarthak Sahoo Arashdeep Singh Sridhar Hannenhalli Prioritizing and characterizing functionally relevant genes across human tissues.
description	Knowledge of genes that are critical to a tissue's function remains difficult to ascertain and presents a major bottleneck toward a mechanistic understanding of genotype-phenotype links. Here, we present the first machine learning model-FUGUE-combining transcriptional and network features, to predict tissue-relevant genes across 30 human tissues. FUGUE achieves an average cross-validation auROC of 0.86 and auPRC of 0.50 (expected 0.09). In independent datasets, FUGUE accurately distinguishes tissue or cell type-specific genes, significantly outperforming the conventional metric based on tissue-specific expression alone. Comparison of tissue-relevant transcription factors across tissue recapitulate their developmental relationships. Interestingly, the tissue-relevant genes cluster on the genome within topologically associated domains and furthermore, are highly enriched for differentially expressed genes in the corresponding cancer type. We provide the prioritized gene lists in 30 human tissues and an open-source software to prioritize genes in a novel context given multi-sample transcriptomic data.
format	article
author	Gowthami Somepalli Sarthak Sahoo Arashdeep Singh Sridhar Hannenhalli
author_facet	Gowthami Somepalli Sarthak Sahoo Arashdeep Singh Sridhar Hannenhalli
author_sort	Gowthami Somepalli
title	Prioritizing and characterizing functionally relevant genes across human tissues.
title_short	Prioritizing and characterizing functionally relevant genes across human tissues.
title_full	Prioritizing and characterizing functionally relevant genes across human tissues.
title_fullStr	Prioritizing and characterizing functionally relevant genes across human tissues.
title_full_unstemmed	Prioritizing and characterizing functionally relevant genes across human tissues.
title_sort	prioritizing and characterizing functionally relevant genes across human tissues.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/ec34913d83af4be5b41ab61cfb9daf94
work_keys_str_mv	AT gowthamisomepalli prioritizingandcharacterizingfunctionallyrelevantgenesacrosshumantissues AT sarthaksahoo prioritizingandcharacterizingfunctionallyrelevantgenesacrosshumantissues AT arashdeepsingh prioritizingandcharacterizingfunctionallyrelevantgenesacrosshumantissues AT sridharhannenhalli prioritizingandcharacterizingfunctionallyrelevantgenesacrosshumantissues
_version_	1718375876357259264

Prioritizing and characterizing functionally relevant genes across human tissues.

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