Top-Down Clustering for Protein Subfamily Identification. (January 2013)

• Record Type: Journal Article
• Authors: Costa, Eduardo P.; Vens, Celine; Blockeel, Hendrik
• Is Part Of: Evolutionary bioinformatics online. Volume 9(2013)
• Publication Date: 2013-01
• Subjects: clustering trees -- top-down clustering -- decision trees -- protein subfamily identification -- phylogenomics; Bioinformatics -- Periodicals; Evolutionary computation -- Periodicals; Genetic programming (Computer science) -- Periodicals; Computational Biology; Evolution, Molecular; Bioinformatics; Electronic journals; Periodicals; Fulltext; Internet Resources; Periodicals; Periodicals; 576.8
• DOI: 10.4137/EBO.S11609
• Languages: English
• ISSNs: 1176-9343

Abstract

We propose a novel method for the task of protein subfamily identification; that is, finding subgroups of functionally closely related sequences within a protein family. In line with phylogenomic analysis, the method first builds a hierarchical tree using as input a multiple alignment of the protein sequences, then uses a post-pruning procedure to extract clusters from the tree. Differently from existing methods, it constructs the hierarchical tree top-down, rather than bottom-up and associates particular mutations with each division into subclusters. The motivating hypothesis for this method is that it may yield a better tree topology with more accurate subfamily identification as a result and additionally indicates functionally important sites and allows for easy classification of new proteins. A thorough experimental evaluation confirms the hypothesis. The novel method yields more accurate clusters and a better tree topology than the state-of-the-art method SCI-PHY, identifies known functional sites, and identifies mutations that alone allow for classifying new sequences with an accuracy approaching that of hidden Markov models.