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These new PPIs provide a more complete view of disease mechanisms but precise understanding of how PPIs affect phenotype remains a challenge. It requires knowledge of PPI context (e.g.\u00a0tissues, subcellular localizations), and functional roles, especially within pathways and protein complexes. The previous IID release focused on PPI context, providing networks with comprehensive tissue, disease, cellular localization, and druggability annotations. The current update adds developmental stages to the available contexts, and provides a way of assigning context to PPIs that could not be previously annotated due to insufficient data or incompatibility with available context categories (e.g.\u00a0interactions between membrane and cytoplasmic proteins). This update also annotates PPIs with conservation across species, directionality in pathways, membership in large complexes, interaction stability (i.e.\u00a0stable or transient), and mutation effects. Enrichment analysis is now available for all annotations, and includes multiple options; for example, context annotations can be analyzed with respect to PPIs or network proteins. In addition to tabular view or download, IID provides online network visualization. This update is available at http:\/\/ophid.utoronto.ca\/iid.<\/jats:p>","DOI":"10.1093\/nar\/gkab1034","type":"journal-article","created":{"date-parts":[[2021,11,5]],"date-time":"2021-11-05T12:23:26Z","timestamp":1636115006000},"page":"D640-D647","source":"Crossref","is-referenced-by-count":74,"title":["IID 2021: towards context-specific protein interaction analyses by increased coverage, enhanced annotation and enrichment analysis"],"prefix":"10.1093","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1111-8667","authenticated-orcid":false,"given":"Max","family":"Kotlyar","sequence":"first","affiliation":[{"name":"Osteoarthritis Research Program, Division of Orthopedic Surgery, Schroeder Arthritis Institute and Data Science Discovery Centre for Chronic Diseases, Krembil Research Institute, University Health Network, Toronto, ON\u00a0M5T 0S8, Canada"}]},{"given":"Chiara","family":"Pastrello","sequence":"additional","affiliation":[{"name":"Osteoarthritis Research Program, Division of Orthopedic Surgery, Schroeder Arthritis Institute and Data Science Discovery Centre for Chronic Diseases, Krembil Research Institute, University Health Network, Toronto, ON\u00a0M5T 0S8, Canada"}]},{"given":"Zuhaib","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Osteoarthritis Research Program, Division of Orthopedic Surgery, Schroeder Arthritis Institute and Data Science Discovery Centre for Chronic Diseases, Krembil Research Institute, University Health Network, Toronto, ON\u00a0M5T 0S8, Canada"}]},{"given":"Justin","family":"Chee","sequence":"additional","affiliation":[{"name":"Osteoarthritis Research Program, Division of Orthopedic Surgery, Schroeder Arthritis Institute and Data Science Discovery Centre for Chronic Diseases, Krembil Research Institute, University Health Network, Toronto, ON\u00a0M5T 0S8, Canada"}]},{"given":"Zofia","family":"Varyova","sequence":"additional","affiliation":[{"name":"Osteoarthritis Research Program, Division of Orthopedic Surgery, Schroeder Arthritis Institute and Data Science Discovery Centre for Chronic Diseases, Krembil Research Institute, University Health Network, Toronto, ON\u00a0M5T 0S8, Canada"}]},{"given":"Igor","family":"Jurisica","sequence":"additional","affiliation":[{"name":"Osteoarthritis Research Program, Division of Orthopedic Surgery, Schroeder Arthritis Institute and Data Science Discovery Centre for Chronic Diseases, Krembil Research Institute, University Health Network, Toronto, ON\u00a0M5T 0S8, Canada"},{"name":"Departments of Medical Biophysics and Computer Science, University of Toronto, Toronto, ON\u00a0M5S 1A4, Canada"},{"name":"Institute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, Slovakia"}]}],"member":"286","published-online":{"date-parts":[[2021,11,10]]},"reference":[{"key":"2022010507393318100_B1","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1093\/bioinformatics\/btq076","article-title":"The power of protein interaction networks for associating genes with diseases","volume":"26","author":"Navlakha","year":"2010","journal-title":"Bioinformatics"},{"key":"2022010507393318100_B2","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1101\/gr.118992.110","article-title":"Prioritizing candidate disease genes by network-based boosting of genome-wide association data","volume":"21","author":"Lee","year":"2011","journal-title":"Genome Res."},{"issue":"Suppl. 1","key":"2022010507393318100_B3","doi-asserted-by":"crossref","first-page":"S7","DOI":"10.1186\/gb-2008-9-s1-s7","article-title":"Combining guilt-by-association and guilt-by-profiling to predict Saccharomyces cerevisiae gene function","volume":"9","author":"Tian","year":"2008","journal-title":"Genome Biol."},{"key":"2022010507393318100_B4","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.1002\/pmic.201100607","article-title":"Combining many interaction networks to predict gene function and analyze gene lists","volume":"12","author":"Mostafavi","year":"2012","journal-title":"Proteomics"},{"key":"2022010507393318100_B5","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.ymeth.2018.06.002","article-title":"Leveraging multiple gene networks to prioritize GWAS candidate genes via network representation learning","volume":"145","author":"Wu","year":"2018","journal-title":"Methods"},{"key":"2022010507393318100_B6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/2043-9113-2-1","article-title":"A network flow approach to predict drug targets from microarray data, disease genes and interactome network - case study on prostate cancer","volume":"2","author":"Yeh","year":"2012","journal-title":"J. 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