Functional annotation of hierarchical modularity.

In biological networks of molecular interactions in a cell, network motifs that are biologically relevant are also functionally coherent, or form functional modules. These functionally coherent modules combine in a hierarchical manner into larger, less cohesive subsystems, thus revealing one of the...

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Autores principales:	Kanchana Padmanabhan, Kuangyu Wang, Nagiza F Samatova
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/42880e5982fb4999aea5d0246f9d2cb6
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spelling	oai:doaj.org-article:42880e5982fb4999aea5d0246f9d2cb62021-11-18T07:23:17ZFunctional annotation of hierarchical modularity.1932-620310.1371/journal.pone.0033744https://doaj.org/article/42880e5982fb4999aea5d0246f9d2cb62012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22496762/?tool=EBIhttps://doaj.org/toc/1932-6203In biological networks of molecular interactions in a cell, network motifs that are biologically relevant are also functionally coherent, or form functional modules. These functionally coherent modules combine in a hierarchical manner into larger, less cohesive subsystems, thus revealing one of the essential design principles of system-level cellular organization and function-hierarchical modularity. Arguably, hierarchical modularity has not been explicitly taken into consideration by most, if not all, functional annotation systems. As a result, the existing methods would often fail to assign a statistically significant functional coherence score to biologically relevant molecular machines. We developed a methodology for hierarchical functional annotation. Given the hierarchical taxonomy of functional concepts (e.g., Gene Ontology) and the association of individual genes or proteins with these concepts (e.g., GO terms), our method will assign a Hierarchical Modularity Score (HMS) to each node in the hierarchy of functional modules; the HMS score and its p-value measure functional coherence of each module in the hierarchy. While existing methods annotate each module with a set of "enriched" functional terms in a bag of genes, our complementary method provides the hierarchical functional annotation of the modules and their hierarchically organized components. A hierarchical organization of functional modules often comes as a bi-product of cluster analysis of gene expression data or protein interaction data. Otherwise, our method will automatically build such a hierarchy by directly incorporating the functional taxonomy information into the hierarchy search process and by allowing multi-functional genes to be part of more than one component in the hierarchy. In addition, its underlying HMS scoring metric ensures that functional specificity of the terms across different levels of the hierarchical taxonomy is properly treated. We have evaluated our method using Saccharomyces cerevisiae data from KEGG and MIPS databases and several other computationally derived and curated datasets. The code and additional supplemental files can be obtained from http://code.google.com/p/functional-annotation-of-hierarchical-modularity/ (Accessed 2012 March 13).Kanchana PadmanabhanKuangyu WangNagiza F SamatovaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 4, p e33744 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kanchana Padmanabhan Kuangyu Wang Nagiza F Samatova Functional annotation of hierarchical modularity.
description	In biological networks of molecular interactions in a cell, network motifs that are biologically relevant are also functionally coherent, or form functional modules. These functionally coherent modules combine in a hierarchical manner into larger, less cohesive subsystems, thus revealing one of the essential design principles of system-level cellular organization and function-hierarchical modularity. Arguably, hierarchical modularity has not been explicitly taken into consideration by most, if not all, functional annotation systems. As a result, the existing methods would often fail to assign a statistically significant functional coherence score to biologically relevant molecular machines. We developed a methodology for hierarchical functional annotation. Given the hierarchical taxonomy of functional concepts (e.g., Gene Ontology) and the association of individual genes or proteins with these concepts (e.g., GO terms), our method will assign a Hierarchical Modularity Score (HMS) to each node in the hierarchy of functional modules; the HMS score and its p-value measure functional coherence of each module in the hierarchy. While existing methods annotate each module with a set of "enriched" functional terms in a bag of genes, our complementary method provides the hierarchical functional annotation of the modules and their hierarchically organized components. A hierarchical organization of functional modules often comes as a bi-product of cluster analysis of gene expression data or protein interaction data. Otherwise, our method will automatically build such a hierarchy by directly incorporating the functional taxonomy information into the hierarchy search process and by allowing multi-functional genes to be part of more than one component in the hierarchy. In addition, its underlying HMS scoring metric ensures that functional specificity of the terms across different levels of the hierarchical taxonomy is properly treated. We have evaluated our method using Saccharomyces cerevisiae data from KEGG and MIPS databases and several other computationally derived and curated datasets. The code and additional supplemental files can be obtained from http://code.google.com/p/functional-annotation-of-hierarchical-modularity/ (Accessed 2012 March 13).
format	article
author	Kanchana Padmanabhan Kuangyu Wang Nagiza F Samatova
author_facet	Kanchana Padmanabhan Kuangyu Wang Nagiza F Samatova
author_sort	Kanchana Padmanabhan
title	Functional annotation of hierarchical modularity.
title_short	Functional annotation of hierarchical modularity.
title_full	Functional annotation of hierarchical modularity.
title_fullStr	Functional annotation of hierarchical modularity.
title_full_unstemmed	Functional annotation of hierarchical modularity.
title_sort	functional annotation of hierarchical modularity.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/42880e5982fb4999aea5d0246f9d2cb6
work_keys_str_mv	AT kanchanapadmanabhan functionalannotationofhierarchicalmodularity AT kuangyuwang functionalannotationofhierarchicalmodularity AT nagizafsamatova functionalannotationofhierarchicalmodularity
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Functional annotation of hierarchical modularity.

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