Functional knowledge transfer for high-accuracy prediction of under-studied biological processes.

A key challenge in genetics is identifying the functional roles of genes in pathways. Numerous functional genomics techniques (e.g. machine learning) that predict protein function have been developed to address this question. These methods generally build from existing annotations of genes to pathwa...

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Autores principales:	Christopher Y Park, Aaron K Wong, Casey S Greene, Jessica Rowland, Yuanfang Guan, Lars A Bongo, Rebecca D Burdine, Olga G Troyanskaya
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/4b1046dff387432187875d3b5d68dd39
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spelling	oai:doaj.org-article:4b1046dff387432187875d3b5d68dd392021-11-18T05:52:21ZFunctional knowledge transfer for high-accuracy prediction of under-studied biological processes.1553-734X1553-735810.1371/journal.pcbi.1002957https://doaj.org/article/4b1046dff387432187875d3b5d68dd392013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23516347/pdf/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358A key challenge in genetics is identifying the functional roles of genes in pathways. Numerous functional genomics techniques (e.g. machine learning) that predict protein function have been developed to address this question. These methods generally build from existing annotations of genes to pathways and thus are often unable to identify additional genes participating in processes that are not already well studied. Many of these processes are well studied in some organism, but not necessarily in an investigator's organism of interest. Sequence-based search methods (e.g. BLAST) have been used to transfer such annotation information between organisms. We demonstrate that functional genomics can complement traditional sequence similarity to improve the transfer of gene annotations between organisms. Our method transfers annotations only when functionally appropriate as determined by genomic data and can be used with any prediction algorithm to combine transferred gene function knowledge with organism-specific high-throughput data to enable accurate function prediction. We show that diverse state-of-art machine learning algorithms leveraging functional knowledge transfer (FKT) dramatically improve their accuracy in predicting gene-pathway membership, particularly for processes with little experimental knowledge in an organism. We also show that our method compares favorably to annotation transfer by sequence similarity. Next, we deploy FKT with state-of-the-art SVM classifier to predict novel genes to 11,000 biological processes across six diverse organisms and expand the coverage of accurate function predictions to processes that are often ignored because of a dearth of annotated genes in an organism. Finally, we perform in vivo experimental investigation in Danio rerio and confirm the regulatory role of our top predicted novel gene, wnt5b, in leftward cell migration during heart development. FKT is immediately applicable to many bioinformatics techniques and will help biologists systematically integrate prior knowledge from diverse systems to direct targeted experiments in their organism of study.Christopher Y ParkAaron K WongCasey S GreeneJessica RowlandYuanfang GuanLars A BongoRebecca D BurdineOlga G TroyanskayaPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 9, Iss 3, p e1002957 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Christopher Y Park Aaron K Wong Casey S Greene Jessica Rowland Yuanfang Guan Lars A Bongo Rebecca D Burdine Olga G Troyanskaya Functional knowledge transfer for high-accuracy prediction of under-studied biological processes.
description	A key challenge in genetics is identifying the functional roles of genes in pathways. Numerous functional genomics techniques (e.g. machine learning) that predict protein function have been developed to address this question. These methods generally build from existing annotations of genes to pathways and thus are often unable to identify additional genes participating in processes that are not already well studied. Many of these processes are well studied in some organism, but not necessarily in an investigator's organism of interest. Sequence-based search methods (e.g. BLAST) have been used to transfer such annotation information between organisms. We demonstrate that functional genomics can complement traditional sequence similarity to improve the transfer of gene annotations between organisms. Our method transfers annotations only when functionally appropriate as determined by genomic data and can be used with any prediction algorithm to combine transferred gene function knowledge with organism-specific high-throughput data to enable accurate function prediction. We show that diverse state-of-art machine learning algorithms leveraging functional knowledge transfer (FKT) dramatically improve their accuracy in predicting gene-pathway membership, particularly for processes with little experimental knowledge in an organism. We also show that our method compares favorably to annotation transfer by sequence similarity. Next, we deploy FKT with state-of-the-art SVM classifier to predict novel genes to 11,000 biological processes across six diverse organisms and expand the coverage of accurate function predictions to processes that are often ignored because of a dearth of annotated genes in an organism. Finally, we perform in vivo experimental investigation in Danio rerio and confirm the regulatory role of our top predicted novel gene, wnt5b, in leftward cell migration during heart development. FKT is immediately applicable to many bioinformatics techniques and will help biologists systematically integrate prior knowledge from diverse systems to direct targeted experiments in their organism of study.
format	article
author	Christopher Y Park Aaron K Wong Casey S Greene Jessica Rowland Yuanfang Guan Lars A Bongo Rebecca D Burdine Olga G Troyanskaya
author_facet	Christopher Y Park Aaron K Wong Casey S Greene Jessica Rowland Yuanfang Guan Lars A Bongo Rebecca D Burdine Olga G Troyanskaya
author_sort	Christopher Y Park
title	Functional knowledge transfer for high-accuracy prediction of under-studied biological processes.
title_short	Functional knowledge transfer for high-accuracy prediction of under-studied biological processes.
title_full	Functional knowledge transfer for high-accuracy prediction of under-studied biological processes.
title_fullStr	Functional knowledge transfer for high-accuracy prediction of under-studied biological processes.
title_full_unstemmed	Functional knowledge transfer for high-accuracy prediction of under-studied biological processes.
title_sort	functional knowledge transfer for high-accuracy prediction of under-studied biological processes.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/4b1046dff387432187875d3b5d68dd39
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Functional knowledge transfer for high-accuracy prediction of under-studied biological processes.

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