Extramurally Speaking Nanotechnology and Nanoengineering

Background: Function prediction by transfer of annotation from the top database hit in a homology search has been shown to be prone to systematic error. Phylogenomic analysis reduces these errors by inferring protein function within the evolutionary context of the entire family. However, accuracy of function prediction for multi-domain proteins depends on all members having the same overall domain structure. By contrast, most common homolog detection methods are optimized for retrieving local homologs, and do not address this requirement. Results: We present FlowerPower, a novel clustering algorithm designed for the identification of global homologs as a precursor to structural phylogenomic analysis. Similar to methods such as PSIBLAST, FlowerPower employs an iterative approach to clustering sequences. However, rather than using a single HMM or profile to expand the cluster, FlowerPower identifies subfamilies using the SCI-PHY algorithm and then selects and aligns new homologs using subfamily hidden Markov models. FlowerPower is shown to outperform BLAST, PSI-BLAST and the UCSC SAM-Target 2K methods at discrimination between proteins in the same domain architecture class and those having different overall domain structures. Conclusion: Structural phylogenomic analysis enables biologists to avoid the systematic errors associated with annotation transfer; clustering sequences based on sharing the same domain architecture is a critical first step in this process. FlowerPower is shown to consistently identify homologous sequences having the same domain architecture as the query. Availability: FlowerPower is available as a webserver at http://phylogenomics.berkeley.edu/ flowerpower/. Introduction Biological processes such as speciation, gene duplication, and domain shuffling produce families of related genes whose gene products can have vastly different molecular functions. Inference of protein function in these cases has been shown to be prone to systematic error [1-3]. Phylogenomic analysis – inferring the function of a protein in the larger context of a protein family based on evolutionary from First International Conference on Phylogenomics Sainte-Adèle, Québec, Canada. 15–19 March, 2006 Published: 8 February 2007 BMC Evolutionary Biology 2007, 7(Suppl 1):S12 doi:10.1186/1471-2148-7-S1-S12 First International Conference on Phylogenomics Hervé Philippe, Mathieu Blanchette Proceedings © 2007 Krishnamurthy et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.