title: IIIDB: a database for isoform-isoform interactions and isoform network modules.
abstract: BACKGROUND
  Protein-protein interactions (PPIs) are key to understanding diverse cellular processes and disease mechanisms. However, current PPI databases only provide low-resolution knowledge of PPIs, in the sense that "proteins" of currently known PPIs generally refer to "genes." It is known that alternative splicing often impacts PPI by either directly affecting protein interacting domains, or by indirectly impacting other domains, which, in turn, impacts the PPI binding. Thus, proteins translated from different isoforms of the same gene can have different interaction partners.
  
  
  RESULTS
  Due to the limitations of current experimental capacities, little data is available for PPIs at the resolution of isoforms, although such high-resolution data is crucial to map pathways and to understand protein functions. In fact, alternative splicing can often change the internal structure of a pathway by rearranging specific PPIs. To fill the gap, we systematically predicted genome-wide isoform-isoform interactions (IIIs) using RNA-seq datasets, domain-domain interaction and PPIs. Furthermore, we constructed an III database (IIIDB) that is a resource for studying PPIs at isoform resolution. To discover functional modules in the III network, we performed III network clustering, and then obtained 1025 isoform modules. To evaluate the module functionality, we performed the GO/pathway enrichment analysis for each isoform module.
  
  
  CONCLUSIONS
  The IIIDB provides predictions of human protein-protein interactions at the high resolution of transcript isoforms that can facilitate detailed understanding of protein functions and biological pathways. The web interface allows users to search for IIIs or III network modules. The IIIDB is freely available at http://syslab.nchu.edu.tw/IIIDB.
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Tseng
authors.forename: Wenyuan
authors.initials: W
authors.lastname: Li
authors.forename: Ching-Hsien
authors.initials: CH
authors.lastname: Chen
authors.forename: Shihua
authors.initials: S
authors.lastname: Zhang
authors.forename: Jeremy J W
authors.initials: JJ
authors.lastname: Chen
authors.forename: Xianghong
authors.initials: X
authors.lastname: Zhou
authors.forename: Chun-Chi
authors.initials: CC
authors.lastname: Liu
mesh_terms: D000465:Algorithms; D017398:Alternative Splicing; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods*; D030562:Databases, Protein; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D020407:Internet; D025941:Protein Interaction Mapping / Q000379:methods*; D060066:Protein Interaction Maps; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D015203:Reproducibility of Results; D012984:Software
chemical_list: D020033:Protein Isoforms; D011506:Proteins