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Title: Functional Annotation of Hierarchical Modularity

Abstract

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 asmore » 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).« less

Authors:
 [1];  [2];  [1]
  1. North Carolina State Univ., Raleigh, NC (United States). Dept. of Computer Science; Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
  2. North Carolina State Univ., Raleigh, NC (United States). Bioinformatics Research Center
Publication Date:
Research Org.:
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
OSTI Identifier:
1627506
Grant/Contract Number:  
AC05-00OR22725
Resource Type:
Accepted Manuscript
Journal Name:
PLoS ONE
Additional Journal Information:
Journal Volume: 7; Journal Issue: 4; Journal ID: ISSN 1932-6203
Publisher:
Public Library of Science
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; Science & Technology - Other Topics

Citation Formats

Padmanabhan, Kanchana, Wang, Kuangyu, and Samatova, Nagiza F. Functional Annotation of Hierarchical Modularity. United States: N. p., 2012. Web. https://doi.org/10.1371/journal.pone.0033744.
Padmanabhan, Kanchana, Wang, Kuangyu, & Samatova, Nagiza F. Functional Annotation of Hierarchical Modularity. United States. https://doi.org/10.1371/journal.pone.0033744
Padmanabhan, Kanchana, Wang, Kuangyu, and Samatova, Nagiza F. Wed . "Functional Annotation of Hierarchical Modularity". United States. https://doi.org/10.1371/journal.pone.0033744. https://www.osti.gov/servlets/purl/1627506.
@article{osti_1627506,
title = {Functional Annotation of Hierarchical Modularity},
author = {Padmanabhan, Kanchana and Wang, Kuangyu and Samatova, Nagiza F.},
abstractNote = {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).},
doi = {10.1371/journal.pone.0033744},
journal = {PLoS ONE},
number = 4,
volume = 7,
place = {United States},
year = {2012},
month = {4}
}

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