Title
Cross-species queries of large gene expression databases.
Abstract
Expression databases, including the Gene Expression Omnibus and ArrayExpress, have experienced significant growth over the past decade and now hold hundreds of thousands of arrays from multiple species. Since most drugs are initially tested on model organisms, the ability to compare expression experiments across species may help identify pathways that are activated in a similar way in humans and other organisms. However, while several methods exist for finding co-expressed genes in the same species as a query gene, looking at co-expression of homologs or arbitrary genes in other species is challenging. Unlike sequence, which is static, expression is dynamic and changes between tissues, conditions and time. Thus, to carry out cross-species analysis using these databases, we need methods that can match experiments in one species with experiments in another species.To facilitate queries in large databases, we developed a new method for comparing expression experiments from different species. We define a distance metric between the ranking of orthologous genes in the two species. We show how to solve an optimization problem for learning the parameters of this function using a training dataset of known similar expression experiments pairs. The function we learn outperforms previous methods and simpler rank comparison methods that have been used in the past for single species analysis. We used our method to compare millions of array pairs from mouse and human expression experiments. The resulting matches can be used to find functionally related genes, to hypothesize about biological response mechanisms and to highlight conditions and diseases that are activating similar pathways in both species.Supporting methods, results and a Matlab implementation are available from http://sb.cs.cmu.edu/ExpQ/.
Year
DOI
Venue
2010
10.1093/bioinformatics/btq451
Bioinformatics
Keywords
Field
DocType
expression experiment,human expression experiment,similar pathway,cross-species query,large gene expression databases,similar expression experiments pair,multiple species,expression databases,cross-species analysis,single species analysis,large databases,different species,gene expression profiling,gene expression,genomics
Gene,Ranking,Computer science,Gene expression,Metric (mathematics),Genomics,Bioinformatics,Model organism,Optimization problem,Database,Gene expression profiling
Journal
Volume
Issue
ISSN
26
19
1367-4811
Citations 
PageRank 
References 
7
0.52
8
Authors
3
Name
Order
Citations
PageRank
Hai-Son Le1664.59
Zoltán N. Oltvai212110.87
Ziv Bar-Joseph31207112.00