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Identification of candidate disease genes by integrating Gene Ontologies and protein-interaction networks: case study of primary immunodeficiencies.

Ortutay, Csaba and Vihinen, Mauno LU (2009) In Nucleic Acids Research 37(2). p.622-628
Abstract
Disease gene identification is still a challenge despite modern high-throughput methods. Many diseases are very rare or lethal and thus cannot be investigated with traditional methods. Several in silico methods have been developed but they have some limitations. We introduce a new method that combines information about protein-interaction network properties and Gene Ontology terms. Genes with high-calculated network scores and statistically significant gene ontology terms based on known diseases are prioritized as candidate genes. The method was applied to identify novel primary immunodeficiency-related genes, 26 of which were found. The investigation uses the protein-interaction network for all essential immunome human genes available in... (More)
Disease gene identification is still a challenge despite modern high-throughput methods. Many diseases are very rare or lethal and thus cannot be investigated with traditional methods. Several in silico methods have been developed but they have some limitations. We introduce a new method that combines information about protein-interaction network properties and Gene Ontology terms. Genes with high-calculated network scores and statistically significant gene ontology terms based on known diseases are prioritized as candidate genes. The method was applied to identify novel primary immunodeficiency-related genes, 26 of which were found. The investigation uses the protein-interaction network for all essential immunome human genes available in the Immunome Knowledge Base and an analysis of their enriched gene ontology annotations. The identified disease gene candidates are mainly involved in cellular signaling including receptors, protein kinases and adaptor and binding proteins as well as enzymes. The method can be generalized for any disease group with sufficient information. (Less)
Please use this url to cite or link to this publication:
author
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Computational Biology: methods, Immunologic Deficiency Syndromes: genetics, Proteins: genetics
in
Nucleic Acids Research
volume
37
issue
2
pages
622 - 628
publisher
Oxford University Press
external identifiers
  • pmid:19073697
  • scopus:59649111554
ISSN
1362-4962
DOI
10.1093/nar/gkn982
language
English
LU publication?
no
id
2b703ed7-a954-432e-b229-ebbfad1c9c07 (old id 3634998)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19073697?dopt=Abstract
date added to LUP
2013-06-12 16:32:06
date last changed
2017-12-10 04:40:59
@article{2b703ed7-a954-432e-b229-ebbfad1c9c07,
  abstract     = {Disease gene identification is still a challenge despite modern high-throughput methods. Many diseases are very rare or lethal and thus cannot be investigated with traditional methods. Several in silico methods have been developed but they have some limitations. We introduce a new method that combines information about protein-interaction network properties and Gene Ontology terms. Genes with high-calculated network scores and statistically significant gene ontology terms based on known diseases are prioritized as candidate genes. The method was applied to identify novel primary immunodeficiency-related genes, 26 of which were found. The investigation uses the protein-interaction network for all essential immunome human genes available in the Immunome Knowledge Base and an analysis of their enriched gene ontology annotations. The identified disease gene candidates are mainly involved in cellular signaling including receptors, protein kinases and adaptor and binding proteins as well as enzymes. The method can be generalized for any disease group with sufficient information.},
  author       = {Ortutay, Csaba and Vihinen, Mauno},
  issn         = {1362-4962},
  keyword      = {Computational Biology: methods,Immunologic Deficiency Syndromes: genetics,Proteins: genetics},
  language     = {eng},
  number       = {2},
  pages        = {622--628},
  publisher    = {Oxford University Press},
  series       = {Nucleic Acids Research},
  title        = {Identification of candidate disease genes by integrating Gene Ontologies and protein-interaction networks: case study of primary immunodeficiencies.},
  url          = {http://dx.doi.org/10.1093/nar/gkn982},
  volume       = {37},
  year         = {2009},
}