Prediction of Human Disease Genes by Human-Mouse Conserved Coexpression Analysis
Identifieur interne : 006982 ( Main/Exploration ); précédent : 006981; suivant : 006983Prediction of Human Disease Genes by Human-Mouse Conserved Coexpression Analysis
Auteurs : Ugo Ala [Italie] ; Rosario Michael Piro [Italie] ; Elena Grassi [Italie] ; Christian Damasco [Italie] ; Lorenzo Silengo [Italie] ; Martin Oti [Pays-Bas] ; Paolo Provero [Italie] ; Ferdinando Di Cunto [Italie]Source :
- PLoS Computational Biology [ 1553-734X ] ; 2008.
Abstract
Even in the post-genomic era, the identification of candidate genes within loci associated with human genetic diseases is a very demanding task, because the critical region may typically contain hundreds of positional candidates. Since genes implicated in similar phenotypes tend to share very similar expression profiles, high throughput gene expression data may represent a very important resource to identify the best candidates for sequencing. However, so far, gene coexpression has not been used very successfully to prioritize positional candidates.
We show that it is possible to reliably identify disease-relevant relationships among genes from massive microarray datasets by concentrating only on genes sharing similar expression profiles in both human and mouse. Moreover, we show systematically that the integration of human-mouse conserved coexpression with a phenotype similarity map allows the efficient identification of disease genes in large genomic regions. Finally, using this approach on 850 OMIM loci characterized by an unknown molecular basis, we propose high-probability candidates for 81 genetic diseases.
Our results demonstrate that conserved coexpression, even at the human-mouse phylogenetic distance, represents a very strong criterion to predict disease-relevant relationships among human genes.
Url:
DOI: 10.1371/journal.pcbi.1000043
PubMed: 18369433
PubMed Central: 2268251
Affiliations:
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nuts="2">Piémont</region></placeName></affiliation></author><author><name sortKey="Grassi, Elena" sort="Grassi, Elena" uniqKey="Grassi E" first="Elena" last="Grassi">Elena Grassi</name><affiliation wicri:level="3"><nlm:aff id="aff1"><addr-line>Molecular Biotechnology Center, Department of Genetics, Biology and Biochemistry, University of Turin, Turin, Italy</addr-line></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea>Molecular Biotechnology Center, Department of Genetics, Biology and Biochemistry, University of Turin, Turin</wicri:regionArea><placeName><settlement type="city">Turin</settlement><region type="région" nuts="2">Piémont</region></placeName></affiliation></author><author><name sortKey="Damasco, Christian" sort="Damasco, Christian" uniqKey="Damasco C" first="Christian" last="Damasco">Christian Damasco</name><affiliation wicri:level="3"><nlm:aff id="aff1"><addr-line>Molecular Biotechnology Center, Department of Genetics, Biology and Biochemistry, University of Turin, Turin, Italy</addr-line></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea>Molecular Biotechnology Center, Department of Genetics, Biology and Biochemistry, University of Turin, Turin</wicri:regionArea><placeName><settlement type="city">Turin</settlement><region type="région" nuts="2">Piémont</region></placeName></affiliation></author><author><name sortKey="Silengo, Lorenzo" sort="Silengo, Lorenzo" uniqKey="Silengo L" first="Lorenzo" last="Silengo">Lorenzo Silengo</name><affiliation wicri:level="3"><nlm:aff id="aff1"><addr-line>Molecular Biotechnology Center, Department of Genetics, Biology and Biochemistry, University of Turin, Turin, Italy</addr-line></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea>Molecular Biotechnology Center, Department of Genetics, Biology and Biochemistry, University of Turin, Turin</wicri:regionArea><placeName><settlement type="city">Turin</settlement><region type="région" nuts="2">Piémont</region></placeName></affiliation></author><author><name sortKey="Oti, Martin" sort="Oti, Martin" uniqKey="Oti M" first="Martin" last="Oti">Martin Oti</name><affiliation wicri:level="3"><nlm:aff id="aff2"><addr-line>Department of Human Genetics and Centre for Molecular and Biomolecular Informatics, University Medical Centre Nijmegen, Nijmegen, The Netherlands</addr-line></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Human Genetics and Centre for Molecular and Biomolecular Informatics, University Medical Centre Nijmegen, Nijmegen</wicri:regionArea><placeName><settlement type="city">Nimègue</settlement><region type="province" nuts="2">Gueldre</region></placeName></affiliation></author><author><name sortKey="Provero, Paolo" sort="Provero, Paolo" uniqKey="Provero P" first="Paolo" last="Provero">Paolo Provero</name><affiliation wicri:level="3"><nlm:aff id="aff1"><addr-line>Molecular Biotechnology Center, Department of Genetics, Biology and Biochemistry, University of Turin, Turin, Italy</addr-line></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea>Molecular Biotechnology Center, Department of Genetics, Biology and Biochemistry, University of Turin, Turin</wicri:regionArea><placeName><settlement type="city">Turin</settlement><region type="région" nuts="2">Piémont</region></placeName></affiliation></author><author><name sortKey="Di Cunto, Ferdinando" sort="Di Cunto, Ferdinando" uniqKey="Di Cunto F" first="Ferdinando" last="Di Cunto">Ferdinando Di Cunto</name><affiliation wicri:level="3"><nlm:aff id="aff1"><addr-line>Molecular Biotechnology Center, Department of Genetics, Biology and Biochemistry, University of Turin, Turin, Italy</addr-line></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea>Molecular Biotechnology Center, Department of Genetics, Biology and Biochemistry, University of Turin, Turin</wicri:regionArea><placeName><settlement type="city">Turin</settlement><region type="région" nuts="2">Piémont</region></placeName></affiliation></author></analytic><series><title level="j">PLoS Computational Biology</title><idno type="ISSN">1553-734X</idno><idno type="eISSN">1553-7358</idno><imprint><date when="2008">2008</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>Even in the post-genomic era, the identification of candidate genes within loci associated with human genetic diseases is a very demanding task, because the critical region may typically contain hundreds of positional candidates. Since genes implicated in similar phenotypes tend to share very similar expression profiles, high throughput gene expression data may represent a very important resource to identify the best candidates for sequencing. However, so far, gene coexpression has not been used very successfully to prioritize positional candidates.</p></sec><sec><title>Methodology/Principal Findings</title><p>We show that it is possible to reliably identify disease-relevant relationships among genes from massive microarray datasets by concentrating only on genes sharing similar expression profiles in both human and mouse. Moreover, we show systematically that the integration of human-mouse conserved coexpression with a phenotype similarity map allows the efficient identification of disease genes in large genomic regions. Finally, using this approach on 850 OMIM loci characterized by an unknown molecular basis, we propose high-probability candidates for 81 genetic diseases.</p></sec><sec><title>Conclusion</title><p>Our results demonstrate that conserved coexpression, even at the human-mouse phylogenetic distance, represents a very strong criterion to predict disease-relevant relationships among human genes.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Van Driel, Ma" uniqKey="Van Driel M">MA van Driel</name></author><author><name sortKey="Brunner, Hg" uniqKey="Brunner H">HG Brunner</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lopez Bigas, N" uniqKey="Lopez Bigas N">N Lopez-Bigas</name></author><author><name sortKey="Ouzounis, Ca" uniqKey="Ouzounis C">CA Ouzounis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Barabasi, Al" uniqKey="Barabasi A">AL 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sortKey="Garcia Ortiz, Je" uniqKey="Garcia Ortiz J">JE Garcia-Ortiz</name></author><author><name sortKey="Banda Espinoza, F" uniqKey="Banda Espinoza F">F Banda-Espinoza</name></author><author><name sortKey="Zenteno, Jc" uniqKey="Zenteno J">JC Zenteno</name></author><author><name sortKey="Galvan Uriarte, Lm" uniqKey="Galvan Uriarte L">LM Galvan-Uriarte</name></author><author><name sortKey="Ruiz Flores, P" uniqKey="Ruiz Flores P">P Ruiz-Flores</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Italie</li><li>Pays-Bas</li></country><region><li>Gueldre</li><li>Piémont</li></region><settlement><li>Nimègue</li><li>Turin</li></settlement></list><tree><country name="Italie"><region name="Piémont"><name sortKey="Ala, Ugo" sort="Ala, Ugo" uniqKey="Ala U" first="Ugo" last="Ala">Ugo Ala</name></region><name sortKey="Damasco, Christian" sort="Damasco, Christian" uniqKey="Damasco C" first="Christian" last="Damasco">Christian Damasco</name><name sortKey="Di Cunto, Ferdinando" sort="Di Cunto, Ferdinando" uniqKey="Di Cunto F" first="Ferdinando" last="Di Cunto">Ferdinando Di Cunto</name><name sortKey="Grassi, Elena" sort="Grassi, Elena" uniqKey="Grassi E" first="Elena" last="Grassi">Elena Grassi</name><name sortKey="Piro, Rosario Michael" sort="Piro, Rosario Michael" uniqKey="Piro R" first="Rosario Michael" last="Piro">Rosario Michael Piro</name><name sortKey="Provero, Paolo" sort="Provero, Paolo" uniqKey="Provero P" first="Paolo" last="Provero">Paolo Provero</name><name sortKey="Silengo, Lorenzo" sort="Silengo, Lorenzo" uniqKey="Silengo L" first="Lorenzo" last="Silengo">Lorenzo Silengo</name></country><country name="Pays-Bas"><region name="Gueldre"><name sortKey="Oti, Martin" sort="Oti, Martin" uniqKey="Oti M" first="Martin" last="Oti">Martin Oti</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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