title: Dissecting the human protein-protein interaction network via phylogenetic decomposition.
abstract: The protein-protein interaction (PPI) network offers a conceptual framework for better understanding the functional organization of the proteome. However, the intricacy of network complexity complicates comprehensive analysis. Here, we adopted a phylogenic grouping method combined with force-directed graph simulation to decompose the human PPI network in a multi-dimensional manner. This network model enabled us to associate the network topological properties with evolutionary and biological implications. First, we found that ancient proteins occupy the core of the network, whereas young proteins tend to reside on the periphery. Second, the presence of age homophily suggests a possible selection pressure may have acted on the duplication and divergence process during the PPI network evolution. Lastly, functional analysis revealed that each age group possesses high specificity of enriched biological processes and pathway engagements, which could correspond to their evolutionary roles in eukaryotic cells. More interestingly, the network landscape closely coincides with the subcellular localization of proteins. Together, these findings suggest the potential of using conceptual frameworks to mimic the true functional organization in a living cell.
authors.affiliation: Genome and Systems Biology Degree Program, Department of Life Science, Institute of Molecular and Cellular Biology.
authors.forename: Cho-Yi
authors.initials: CY
authors.lastname: Chen
authors.affiliation: Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei 10617, Taiwan.
authors.forename: Andy
authors.initials: A
authors.lastname: Ho
authors.affiliation: Taipei Municipal Jianguo High School, Taipei 10066, Taiwan.
authors.forename: Hsin-Yuan
authors.initials: HY
authors.lastname: Huang
authors.affiliation: 1] Genome and Systems Biology Degree Program, Department of Life Science, Institute of Molecular and Cellular Biology [2] Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei 10617, Taiwan.
authors.forename: Hsueh-Fen
authors.initials: HF
authors.lastname: Juan
authors.affiliation: Institute of Biomedical Informatics, Center for Systems and Synthetic Biology, National Yang-Ming University, Taipei 11221, Taiwan.
authors.forename: Hsuan-Cheng
authors.initials: HC
authors.lastname: Huang
mesh_terms: D019143:Evolution, Molecular; D006801:Humans; D008958:Models, Molecular; D010802:Phylogeny; D060066:Protein Interaction Maps; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D020543:Proteome; D013997:Time Factors
chemical_list: D011506:Proteins; D020543:Proteome