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Functional genome annotation through phylogenomic mapping

Nature Biotechnology volume 23, pages 691–698 (2005)Cite this article

Abstract

Accurate determination of functional interactions among proteins at the genome level remains a challenge for genomic research. Here we introduce a genome-scale approach to functional protein annotation—phylogenomic mapping—that requires only sequence data, can be applied equally well to both finished and unfinished genomes, and can be extended beyond single genomes to annotate multiple genomes simultaneously. We have developed and applied it to more than 200 sequenced bacterial genomes. Proteins with similar evolutionary histories were grouped together, placed on a three dimensional map and visualized as a topographical landscape. The resulting phylogenomic maps display thousands of proteins clustered in mountains on the basis of coinheritance, a strong indicator of shared function. In addition to systematic computational validation, we have experimentally confirmed the ability of phylogenomic maps to predict both mutant phenotype and gene function in the delta proteobacterium Myxococcus xanthus.

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Figure 1: Phylogenomic mapping.
Figure 2: The phylogenomic map of M. xanthus.
Figure 3: Experimental validation of phylogenomic map predictions in M. xanthus.

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Acknowledgements

We thank Harley McAdams, Lucy Shapiro, William Nierman and Dale Kaiser for helpful discussions. We thank the Monsanto Corporation and the Institute for Genomics Research for providing access to the genome sequence of M. xanthus DK1622. This work was supported in part by National Science Foundation (NSF) Grant MCB-0444154 to A.G.G. B.S.S. was supported by a Department of Defense National Defense Science and Engineering Graduate Fellowship through the Army Research Office. Sequencing of M. xanthus DK1622 was accomplished with support from the NSF.

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Authors and Affiliations

  1. Department of Developmental Biology, Stanford University School of Medicine, Stanford, California, USA

    Balaji S Srinivasan

  2. Department of Electrical Engineering, Stanford University, Stanford, California

    Balaji S Srinivasan

  3. Department of Biology, Syracuse University, 130 College Place, BRL Room 702A, Syracuse, 13244-1170, New York, USA

    Nora B Caberoy, Garret Suen, Rion G Taylor, Radhika Shah, Farah Tengra, Anthony G Garza & Roy D Welch

  4. Monsanto Corporation, St. Louis, Missouri, USA

    Barry S Goldman

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  1. Balaji S Srinivasan
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Correspondence to Roy D Welch.

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Supplementary information

Supplementary Table 1

Global computational validation of phylogenomic mapping (PDF 153 kb)

Supplementary Note 1

Similarity matrix generation (PDF 91 kb)

Supplementary Note 2

Motility assays and plasmid insertion (PDF 54 kb)

Supplementary Note 3

Gene ontology analysis (PDF 61 kb)

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Srinivasan, B., Caberoy, N., Suen, G. et al. Functional genome annotation through phylogenomic mapping. Nat Biotechnol 23, 691–698 (2005). https://doi.org/10.1038/nbt1098

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