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Bioinformatics Advance Access published online on September 30, 2004
Bioinformatics, doi:10.1093/bioinformatics/bti045
Bioinformatics © Oxford University Press 2004; all rights reserved
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Received May 27, 2004
Revised September 20, 2004
Accepted September 21, 2004

Article

Using shared genomic synteny and shared protein functions to enhance the identification of orthologous gene pairs

Xiangqun H. Zheng 1, Fu Lu 1, Zhen-Yuan Wang 1, Fei Zhong 1, Jeffrey Hoover 1, and Richard Mural 1*

1 Assays and Bioinformatics, Celera Genomics, 45 West Gude Drive, Rockville, Maryland 20850, USA

* To whom correspondence should be addressed. E-mail: richard.mural{at}celera.com.


  Abstract

Motivation: The identification of orthologous gene pairs is generally based on sequence similarity. Gene pairs that are mutually "best hits" between the genomes being compared are asserted to be orthologs. While this method identifies most orthologous gene pairs with high confidence, it will miss a fraction of ortholog pairs, especially genes in duplicated gene families. In addition, the approach depends heavily on the completeness and the quality of gene annotation. When the gene sequences are not correctly represented the approach is unlikely to find the correct ortholog. To overcome these limitations, we have developed an approach to identify orthologous gene pairs using shared chromosomal synteny and the annotation of protein function.

Results: Assembled mouse and human genomes (Mural et al., 2002; Venter et al., 2001) were used to identify the regions of conserved synteny between these genomes. "Syntenic anchors" are conserved non-repetitive locations between mouse and human genomes. Using these anchors, we identified blocks of sequences that contain consistently ordered anchors between the two genomes (syntenic blocks). The synteny information has been used to help us identify orthologous gene pairs between mouse and human. The approach combines selecting mutually best tBlastX hits among human and mouse transcripts, and inferring gene orthologous relationships based on sharing syntenic anchors, co-locating in the same syntenic blocks, and sharing the same annotated protein function. Using this approach, we are able to find 19357 orthologous gene pairs between human and mouse, a 20% increase over the number of orthologs identified by conventional approaches.

Supplementary information: A table containing human mouse orthologs on mouse chromosome 16 can be found in THIS URL (editor, please provide a URL).


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