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Using Human Differentially Expressed Gene Lists to Perform Downstream Pathway Enrichment Analysis and Target Prioritization

Using Human Differentially Expressed Gene Lists to Perform Downstream Pathway Enrichment Analysis and Target Prioritization

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Integrating human omics data to prioritize candidate genes.

Yong Chen, Xuebing Wu, Rui Jiang¹

¹Department of Automation, MOE Key Laboratory of Bioinformatics; Bioinformatics Division and Center for Synthetic & Systems Biology, TNLIST, Tsinghua University, Beijing 100084, China. ruijiang@tsinghua.edu.cn.

BMC Medical Genomics

|December 19, 2013

Summary

This summary is machine-generated.

We developed BRIDGE, a novel computational method that integrates multiple omics data to identify candidate disease genes. This approach significantly improves the accuracy of gene prioritization for complex human diseases.

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Area of Science:

Computational Systems Biology
Genomics
Bioinformatics

Background:

Identifying genes for complex human diseases is a significant challenge.
Existing methods often overlook valuable omics data, focusing primarily on protein-protein interactions and phenotypic similarities.

Purpose of the Study:

To propose BRIDGE, a method for prioritizing candidate genes by integrating diverse omics data.
To identify genes associated with diseases, even when their genetic basis is unknown.

Main Methods:

BRIDGE integrates disease phenotypic similarities with multiple omics data: protein-protein interactions, gene sequence similarities, gene expression, gene ontology, and pathway memberships.
A multiple regression model with lasso penalty is used to automatically weight different data sources.

Main Results:

Large-scale cross-validation showed BRIDGE ranks over 60% of known disease genes as top candidates.
Case studies on obesity and type II diabetes successfully predicted novel genes and transcriptional networks.

Conclusions:

BRIDGE offers an effective and scalable approach for integrating multi-omics data to infer disease genes.
Future applications of BRIDGE can uncover novel disease genes and elucidate underlying disease mechanisms.