{"doi":"10.1371/journal.pcbi.1005717","title":"Domain-based prediction of the human isoform interactome provides insights into the functional impact of alternative splicing","abstract":null,"journal":"PLOS Computational Biology","year":2017,"id":636854,"datarank":0.5606504427425053,"base_score":3.7376696182833684,"endowment":3.7376696182833684,"self_citation_contribution":0.5606504427425053,"citation_network_contribution":0.0,"self_endowment_contribution":0.5606504427425053,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":41,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1653283,"name":"Luke Lambourne","orcid":null,"position":1,"is_corresponding":false},{"id":56381,"name":"Marc Vidal","orcid":"0000-0003-3391-5410","position":2,"is_corresponding":false},{"id":106268,"name":"Yu Xia","orcid":"0000-0002-5596-5518","position":3,"is_corresponding":false},{"id":1653282,"name":"Mohamed Ali Ghadie","orcid":"0000-0001-8300-7360","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Domain-based prediction of the human isoform interactome provides insights into the functional impact of alternative splicing","abstract":"Alternative splicing is known to remodel protein-protein interaction networks (\"interactomes\"), yet large-scale determination of isoform-specific interactions remains challenging. We present a domain-based method to predict the isoform interactome from the reference interactome. First, we construct the domain-resolved reference interactome by mapping known domain-domain interactions onto experimentally-determined interactions between reference proteins. Then, we construct the isoform interactome by predicting that an isoform loses an interaction if it loses the domain mediating the interaction. Our prediction framework is of high-quality when assessed by experimental data. The predicted human isoform interactome reveals extensive network remodeling by alternative splicing. Protein pairs interacting with different isoforms of the same gene tend to be more divergent in biological function, tissue expression, and disease phenotype than protein pairs interacting with the same isoforms. Our prediction method complements experimental efforts, and demonstrates that integrating structural domain information with interactomes provides insights into the functional impact of alternative splicing.","is_dataset_classified":null,"base_score":3.7376696182833684,"endowment":3.7376696182833684,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"28846689","pmcid":"PMC5591010","openalex_id":"https://openalex.org/W2749136581","authors":[],"funders":[{"funder_name":"Natural Sciences and Engineering Research Council of Canada (CA)","grant_id":"RGPIN-2014-03892","title":null},{"funder_name":"Canada Foundation for Innovation (CA)","grant_id":"JELF-33732","title":null},{"funder_name":"National Human Genome Research Institute (US)","grant_id":"P50HG004233","title":null},{"funder_name":"National Human Genome Research Institute (US)","grant_id":"U01HG001715","title":null},{"funder_name":"National Cancer Institute","grant_id":"R33CA132073","title":null},{"funder_name":"National Institutes of Health","grant_id":"5R33CA132073-02","title":"Application of Technologies for Interactome Network Analyses of Cancer Mutations"},{"funder_name":"Natural Sciences and Engineering Research Council of Canada","grant_id":"unidentified","title":"unidentified"},{"funder_name":"National Institutes of Health","grant_id":"5U01HG001715-16","title":"Mapping the first half of the REFERENCE human binary protein interactome"},{"funder_name":"National Institutes of Health","grant_id":"5P50HG004233-08","title":"Genomic Analysis of Network Perturbations in Human Disease"},{"funder_name":"The Ellison Foundation","grant_id":"","title":null},{"funder_name":"Canada Research Chairs (CA)","grant_id":"","title":null}],"total_grants":11,"fwci":1.4196,"citation_percentile":0.81416834,"influential_citations":0,"citation_trend":[{"year":2018,"count":1},{"year":2019,"count":5},{"year":2020,"count":8},{"year":2021,"count":5},{"year":2022,"count":6},{"year":2023,"count":4},{"year":2024,"count":6},{"year":2025,"count":3},{"year":2026,"count":3}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1005717&type=printable","host_type":"journal"},{"url":"https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1005717&type=printable","host_type":"publisher"},{"url":"http://dx.plos.org/10.1371/journal.pcbi.1005717","host_type":"publisher"},{"url":"https://doi.org/10.1371/journal.pcbi.1005717","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/28846689","host_type":"repository"},{"url":"http://nrs.harvard.edu/urn-3:HUL.InstRepos:34492024","host_type":"repository"},{"url":"https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1005717","host_type":"repository"},{"url":"http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=147850","host_type":"repository"},{"url":"https://doaj.org/article/28fc2a3fb6e84d468938b4192309de5a","host_type":"repository"},{"url":"https://escholarship.mcgill.ca/concern/articles/kd17cz09n","host_type":"repository"},{"url":"https://figshare.com/articles/dataset/Domain-based_prediction_of_the_human_isoform_interactome_provides_insights_into_the_functional_impact_of_alternative_splicing/5352592","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/5591010","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC5591010","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC5591010?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.1371/journal.pcbi.1005717","host_type":""},{"url":"https://dx.doi.org/10.1371/journal.pcbi.1005717","host_type":""},{"url":"https://doi.org/https://doi.org/10.1371/journal.pcbi.1005717","host_type":""}],"fields_of_study":["RNA Research and Splicing","Bioinformatics and Genomic Networks","RNA and protein synthesis mechanisms","0301 basic medicine","03 medical and health sciences","0303 health sciences","Alternative Splicing","Computational Biology","Humans","Models, Statistical","Neoplasms","Protein Interaction Mapping","Protein Interaction Maps","Protein Isoforms"],"mesh_terms":["Humans","Neoplasms","Models, Statistical","Alternative Splicing","Computational Biology","Protein Isoforms","Protein Interaction Mapping","Protein Interaction Maps"],"keywords":["Interactome","Alternative splicing","Gene isoform","Computational biology","Protein–protein interaction","RNA splicing","Biology","Protein domain","Domain (mathematical analysis)","Bioinformatics","Genetics","Gene","Proteomics","570","Computer and Information Sciences","QH301-705.5","610","Apoptosis","Biochemistry","Mathematical and Statistical Techniques","Protein Domains","Neoplasms","Protein Interaction Mapping","Humans","Protein Isoforms","Protein Interaction Maps","Statistical Methods","Biology (General)","Protein Interactions","Models, Statistical","Biology and life sciences","Cell Death","Gene Ontologies","Proteins","Genomics","Cell Biology","Genome Analysis","Nucleic acids","RNA processing","Protein-Protein Interactions","Cell Processes","Physical Sciences","RNA","Protein Interaction Networks","Gene expression","Network Analysis","Mathematics","Statistics (Mathematics)","Forecasting","Research Article"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"uniprot"},{"name":"pdb"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T17:50:54.756203Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}