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          Institute: MPI für molekulare Genetik     Collection: Department of Vertebrate Genomics     Display Documents



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ID: 411302.0, MPI für molekulare Genetik / Department of Vertebrate Genomics
Meta-analysis approach identifies candidate genes and associated molecular networks for Type-2 Diabetes Mellitus
Authors:Rasche, Axel; Al-Hasani, Hadi; Herwig, Ralf
Language:English
Date of Publication (YYYY-MM-DD):2008-06-30
Title of Journal:BMC Genomics
Volume:9
Start Page:9:310
End Page:9:310
Copyright:© 2008 Rasche et al; licensee BioMed Central Ltd
Review Status:not specified
Audience:Experts Only
Abstract / Description:Background

Multiple functional genomics data for complex human diseases have been published and made available by researchers worldwide. The main goal of these studies is the detailed analysis of a particular aspect of the disease. Complementary, meta-analysis approaches try to extract supersets of disease genes and interaction networks by integrating and combining these individual studies using statistical approaches.

Results

Here we report on a meta-analysis approach that integrates data of heterogeneous origin in the domain of type-2 diabetes mellitus (T2DM). Different data sources such as DNA microarrays and, complementing, qualitative data covering several human and mouse tissues are integrated and analyzed with a Bootstrap scoring approach in order to extract disease relevance of the genes. The purpose of the meta-analysis is two-fold: on the one hand it identifies a group of genes with overall disease relevance indicating common, tissue-independent processes related to the disease; on the other hand it identifies genes showing specific alterations with respect to a single study. Using a random sampling approach we computed a core set of 213 T2DM genes across multiple tissues in human and mouse, including well-known genes such as Pdk4, Adipoq, Scd, Pik3r1, Socs2 that monitor important hallmarks of T2DM, for example the strong relationship between obesity and insulin resistance, as well as a large fraction (128) of yet barely characterized novel candidate genes. Furthermore, we explored functional information and identified cellular networks associated with this core set of genes such as pathway information, protein-protein interactions and gene regulatory networks. Additionally, we set up a web interface in order to allow users to screen T2DM relevance for any – yet non-associated – gene.

Conclusion

In our paper we have identified a core set of 213 T2DM candidate genes by a meta-analysis of existing data sources. We have explored the relation of these genes to disease relevant information and – using enrichment analysis – we have identified biological networks on different layers of cellular information such as signaling and metabolic pathways, gene regulatory networks and protein-protein interactions. The web interface is accessible via http://t2dm-geneminer.molgen.mpg.de webcite.
External Publication Status:published
Document Type:Article
Communicated by:Hans Lehrach
Affiliations:MPI für molekulare Genetik
External Affiliations:German Institute for Human Nutrition, Potsdam-Rehbrücke, Arthur-Scheunert-Allee 114-116, D-14558 Nuthetal, Germany
Identifiers:ISSN:1471-2164
DOI:10.1186/1471-2164-9-310
URL:http://www.biomedcentral.com/content/pdf/1471-2164...
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