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An integrative network-based approach to identify novel disease genes and pathways: a case study in the context of inflammatory bowel disease

BACKGROUND: There are different and complicated associations between genes and diseases. Finding the causal associations between genes and specific diseases is still challenging. In this work we present a method to predict novel associations of genes and pathways with inflammatory bowel disease (IBD...

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Autores principales: Eguchi, Ryohei, Karim, Mohammand Bozlul, Hu, Pingzhao, Sato, Tetsuo, Ono, Naoaki, Kanaya, Shigehiko, Altaf-Ul-Amin, Md.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6043997/
https://www.ncbi.nlm.nih.gov/pubmed/30005591
http://dx.doi.org/10.1186/s12859-018-2251-x
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author Eguchi, Ryohei
Karim, Mohammand Bozlul
Hu, Pingzhao
Sato, Tetsuo
Ono, Naoaki
Kanaya, Shigehiko
Altaf-Ul-Amin, Md.
author_facet Eguchi, Ryohei
Karim, Mohammand Bozlul
Hu, Pingzhao
Sato, Tetsuo
Ono, Naoaki
Kanaya, Shigehiko
Altaf-Ul-Amin, Md.
author_sort Eguchi, Ryohei
collection PubMed
description BACKGROUND: There are different and complicated associations between genes and diseases. Finding the causal associations between genes and specific diseases is still challenging. In this work we present a method to predict novel associations of genes and pathways with inflammatory bowel disease (IBD) by integrating information of differential gene expression, protein-protein interaction and known disease genes related to IBD. RESULTS: We downloaded IBD gene expression data from NCBI’s Gene Expression Omnibus, performed statistical analysis to determine differentially expressed genes, collected known IBD genes from DisGeNet database, which were used to construct a IBD related PPI network with HIPPIE database. We adapted our graph-based clustering algorithm DPClusO to cluster the disease PPI network. We evaluated the statistical significance of the identified clusters in the context of determining the richness of IBD genes using Fisher’s exact test and predicted novel genes related to IBD. We showed 93.8% of our predictions are correct in the context of other databases and published literatures related to IBD. CONCLUSIONS: Finding disease-causing genes is necessary for developing drugs with synergistic effect targeting many genes simultaneously. Here we present an approach to identify novel disease genes and pathways and discuss our approach in the context of IBD. The approach can be generalized to find disease-associated genes for other diseases. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12859-018-2251-x) contains supplementary material, which is available to authorized users.
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spelling pubmed-60439972018-07-13 An integrative network-based approach to identify novel disease genes and pathways: a case study in the context of inflammatory bowel disease Eguchi, Ryohei Karim, Mohammand Bozlul Hu, Pingzhao Sato, Tetsuo Ono, Naoaki Kanaya, Shigehiko Altaf-Ul-Amin, Md. BMC Bioinformatics Research Article BACKGROUND: There are different and complicated associations between genes and diseases. Finding the causal associations between genes and specific diseases is still challenging. In this work we present a method to predict novel associations of genes and pathways with inflammatory bowel disease (IBD) by integrating information of differential gene expression, protein-protein interaction and known disease genes related to IBD. RESULTS: We downloaded IBD gene expression data from NCBI’s Gene Expression Omnibus, performed statistical analysis to determine differentially expressed genes, collected known IBD genes from DisGeNet database, which were used to construct a IBD related PPI network with HIPPIE database. We adapted our graph-based clustering algorithm DPClusO to cluster the disease PPI network. We evaluated the statistical significance of the identified clusters in the context of determining the richness of IBD genes using Fisher’s exact test and predicted novel genes related to IBD. We showed 93.8% of our predictions are correct in the context of other databases and published literatures related to IBD. CONCLUSIONS: Finding disease-causing genes is necessary for developing drugs with synergistic effect targeting many genes simultaneously. Here we present an approach to identify novel disease genes and pathways and discuss our approach in the context of IBD. The approach can be generalized to find disease-associated genes for other diseases. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12859-018-2251-x) contains supplementary material, which is available to authorized users. BioMed Central 2018-07-13 /pmc/articles/PMC6043997/ /pubmed/30005591 http://dx.doi.org/10.1186/s12859-018-2251-x Text en © The Author(s) 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License(http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Eguchi, Ryohei
Karim, Mohammand Bozlul
Hu, Pingzhao
Sato, Tetsuo
Ono, Naoaki
Kanaya, Shigehiko
Altaf-Ul-Amin, Md.
An integrative network-based approach to identify novel disease genes and pathways: a case study in the context of inflammatory bowel disease
title An integrative network-based approach to identify novel disease genes and pathways: a case study in the context of inflammatory bowel disease
title_full An integrative network-based approach to identify novel disease genes and pathways: a case study in the context of inflammatory bowel disease
title_fullStr An integrative network-based approach to identify novel disease genes and pathways: a case study in the context of inflammatory bowel disease
title_full_unstemmed An integrative network-based approach to identify novel disease genes and pathways: a case study in the context of inflammatory bowel disease
title_short An integrative network-based approach to identify novel disease genes and pathways: a case study in the context of inflammatory bowel disease
title_sort integrative network-based approach to identify novel disease genes and pathways: a case study in the context of inflammatory bowel disease
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6043997/
https://www.ncbi.nlm.nih.gov/pubmed/30005591
http://dx.doi.org/10.1186/s12859-018-2251-x
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