title: A protein domain co-occurrence network approach for predicting protein function and inferring species phylogeny.
abstract: Protein Domain Co-occurrence Network (DCN) is a biological network that has not been fully-studied. We analyzed the properties of the DCNs of H. sapiens, S. cerevisiae, C. elegans, D. melanogaster, and 15 plant genomes. These DCNs have the hallmark features of scale-free networks. We investigated the possibility of using DCNs to predict protein and domain functions. Based on our experiment conducted on 66 randomly selected proteins, the best of top 3 predictions made by our DCN-based aggregated neighbor-counting method achieved a semantic similarity score of 0.81 to the actual Gene Ontology terms of the proteins. Moreover, the top 3 predictions using neighbor-counting, χ(2), and a SVM-based method achieved an accuracy of 66%, 59%, and 61%, respectively, when used to predict specific Gene Ontology terms of human target domains. These predictions on average had a semantic similarity score of 0.82, 0.80, and 0.79 to the actual Gene Ontology terms, respectively. We also used DCNs to predict whether a domain is an enzyme domain, and our SVM-based and neighbor-inference method correctly classified 79% and 77% of the target domains, respectively. When using DCNs to classify a target domain into one of the six enzyme classes, we found that, as long as there is one EC number available in the neighboring domains, our SVM-based and neighboring-counting method correctly classified 92.4% and 91.9% of the target domains, respectively. Furthermore, we benchmarked the performance of using DCNs to infer species phylogenies on six different combinations of 398 single-chromosome prokaryotic genomes. The phylogenetic tree of 54 prokaryotic taxa generated by our DCNs-alignment-based method achieved a 93.45% similarity score compared to the Bergey's taxonomy. In summary, our studies show that genome-wide DCNs contain rich information that can be effectively used to decipher protein function and reveal the evolutionary relationship among species.
authors: Department of Computer Science, University of Missouri, Columbia, Missouri, United States of America.
authors: Zheng
authors: Z
authors: Wang
authors: Xue-Cheng
authors: XC
authors: Zhang
authors: Mi Ha
authors: MH
authors: Le
authors: Dong
authors: D
authors: Xu
authors: Gary
authors: G
authors: Stacey
authors: Jianlin
authors: J
authors: Cheng
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics; D019295:Computational Biology; D004331:Drosophila melanogaster / Q000235:genetics; D006801:Humans; D010802:Phylogeny; D010944:Plants / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D011506:Proteins / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000235:genetics
chemical_list: D011506:Proteins