A protein domain Co-occurrence network approach for predicting protein function and inferring species phylogeny

Zheng Wang, Xue Cheng Zhang, Mi Ha Le, Dong Xu, Gary Stacey, Jianlin Cheng

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


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, χ2, 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.

Original languageEnglish (US)
Article numbere17906
JournalPloS one
Issue number3
StatePublished - 2011
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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