Predicting protein function with hierarchical phylogenetic profiles: the Gene3D Phylo-Tuner method applied to eukaryotic genomes.

"Phylogenetic profiling" is based on the hypothesis that during evolution functionally or physically interacting genes are likely to be inherited or eliminated in a codependent manner. Creating presence-absence profiles of orthologous genes is now a common and powerful way of identifying f...

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Autores principales:	Juan A G Ranea, Corin Yeats, Alastair Grant, Christine A Orengo
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2007
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/5fe635ad0744482caa21b2317c2b80ef
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spelling	oai:doaj.org-article:5fe635ad0744482caa21b2317c2b80ef2021-11-25T05:41:30ZPredicting protein function with hierarchical phylogenetic profiles: the Gene3D Phylo-Tuner method applied to eukaryotic genomes.1553-734X1553-735810.1371/journal.pcbi.0030237https://doaj.org/article/5fe635ad0744482caa21b2317c2b80ef2007-11-01T00:00:00Zhttps://doi.org/10.1371/journal.pcbi.0030237https://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358"Phylogenetic profiling" is based on the hypothesis that during evolution functionally or physically interacting genes are likely to be inherited or eliminated in a codependent manner. Creating presence-absence profiles of orthologous genes is now a common and powerful way of identifying functionally associated genes. In this approach, correctly determining orthology, as a means of identifying functional equivalence between two genes, is a critical and nontrivial step and largely explains why previous work in this area has mainly focused on using presence-absence profiles in prokaryotic species. Here, we demonstrate that eukaryotic genomes have a high proportion of multigene families whose phylogenetic profile distributions are poor in presence-absence information content. This feature makes them prone to orthology mis-assignment and unsuited to standard profile-based prediction methods. Using CATH structural domain assignments from the Gene3D database for 13 complete eukaryotic genomes, we have developed a novel modification of the phylogenetic profiling method that uses genome copy number of each domain superfamily to predict functional relationships. In our approach, superfamilies are subclustered at ten levels of sequence identity-from 30% to 100%-and phylogenetic profiles built at each level. All the profiles are compared using normalised Euclidean distances to identify those with correlated changes in their domain copy number. We demonstrate that two protein families will "auto-tune" with strong co-evolutionary signals when their profiles are compared at the similarity levels that capture their functional relationship. Our method finds functional relationships that are not detectable by the conventional presence-absence profile comparisons, and it does not require a priori any fixed criteria to define orthologous genes.Juan A G RaneaCorin YeatsAlastair GrantChristine A OrengoPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 3, Iss 11, p e237 (2007)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Juan A G Ranea Corin Yeats Alastair Grant Christine A Orengo Predicting protein function with hierarchical phylogenetic profiles: the Gene3D Phylo-Tuner method applied to eukaryotic genomes.
description	"Phylogenetic profiling" is based on the hypothesis that during evolution functionally or physically interacting genes are likely to be inherited or eliminated in a codependent manner. Creating presence-absence profiles of orthologous genes is now a common and powerful way of identifying functionally associated genes. In this approach, correctly determining orthology, as a means of identifying functional equivalence between two genes, is a critical and nontrivial step and largely explains why previous work in this area has mainly focused on using presence-absence profiles in prokaryotic species. Here, we demonstrate that eukaryotic genomes have a high proportion of multigene families whose phylogenetic profile distributions are poor in presence-absence information content. This feature makes them prone to orthology mis-assignment and unsuited to standard profile-based prediction methods. Using CATH structural domain assignments from the Gene3D database for 13 complete eukaryotic genomes, we have developed a novel modification of the phylogenetic profiling method that uses genome copy number of each domain superfamily to predict functional relationships. In our approach, superfamilies are subclustered at ten levels of sequence identity-from 30% to 100%-and phylogenetic profiles built at each level. All the profiles are compared using normalised Euclidean distances to identify those with correlated changes in their domain copy number. We demonstrate that two protein families will "auto-tune" with strong co-evolutionary signals when their profiles are compared at the similarity levels that capture their functional relationship. Our method finds functional relationships that are not detectable by the conventional presence-absence profile comparisons, and it does not require a priori any fixed criteria to define orthologous genes.
format	article
author	Juan A G Ranea Corin Yeats Alastair Grant Christine A Orengo
author_facet	Juan A G Ranea Corin Yeats Alastair Grant Christine A Orengo
author_sort	Juan A G Ranea
title	Predicting protein function with hierarchical phylogenetic profiles: the Gene3D Phylo-Tuner method applied to eukaryotic genomes.
title_short	Predicting protein function with hierarchical phylogenetic profiles: the Gene3D Phylo-Tuner method applied to eukaryotic genomes.
title_full	Predicting protein function with hierarchical phylogenetic profiles: the Gene3D Phylo-Tuner method applied to eukaryotic genomes.
title_fullStr	Predicting protein function with hierarchical phylogenetic profiles: the Gene3D Phylo-Tuner method applied to eukaryotic genomes.
title_full_unstemmed	Predicting protein function with hierarchical phylogenetic profiles: the Gene3D Phylo-Tuner method applied to eukaryotic genomes.
title_sort	predicting protein function with hierarchical phylogenetic profiles: the gene3d phylo-tuner method applied to eukaryotic genomes.
publisher	Public Library of Science (PLoS)
publishDate	2007
url	https://doaj.org/article/5fe635ad0744482caa21b2317c2b80ef
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Predicting protein function with hierarchical phylogenetic profiles: the Gene3D Phylo-Tuner method applied to eukaryotic genomes.

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