{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T18:36:19Z","timestamp":1773340579864,"version":"3.50.1"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"Supplement_1","license":[{"start":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T00:00:00Z","timestamp":1688083200000},"content-version":"vor","delay-in-days":29,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Klaus Tschira Stiftung gGmbH","award":["00.013.2021"],"award-info":[{"award-number":["00.013.2021"]}]},{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Christoph Dieterich for the CRC\/SFB 1550"},{"name":"Informatics for Life consortium"},{"name":"Klaus Tschira Stiftung gGmbH"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,6,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>Alternative RNA splicing plays a crucial role in defining protein function. However, despite its relevance, there is a lack of tools that characterize effects of splicing on protein interaction networks in a mechanistic manner (i.e. presence or absence of protein\u2013protein interactions due to RNA splicing). To fill this gap, we present Linear Integer programming for Network reconstruction using transcriptomics and Differential splicing data Analysis (LINDA) as a method that integrates resources of protein\u2013protein and domain\u2013domain interactions, transcription factor targets, and differential splicing\/transcript analysis to infer splicing-dependent effects on cellular pathways and regulatory networks.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We have applied LINDA to a panel of 54 shRNA depletion experiments in HepG2 and K562 cells from the ENCORE initiative. Through computational benchmarking, we could show that the integration of splicing effects with LINDA can identify pathway mechanisms contributing to known bioprocesses better than other state of the art methods, which do not account for splicing. Additionally, we have experimentally validated some of the predicted splicing effects that the depletion of HNRNPK in K562 cells has on signalling.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btad224","type":"journal-article","created":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T08:17:59Z","timestamp":1688113079000},"page":"i458-i464","source":"Crossref","is-referenced-by-count":9,"title":["Characterizing alternative splicing effects on protein interaction networks with LINDA"],"prefix":"10.1093","volume":"39","author":[{"given":"Enio","family":"Gjerga","sequence":"first","affiliation":[{"name":"Section of Bioinformatics and Systems Cardiology, Klaus Tschira Institute for Integrative Computational Cardiology, University Hospital Heidelberg , Heidelberg 69120, Germany"},{"name":"Department of Internal Medicine III (Cardiology, Angiology, and Pneumology), University Hospital Heidelberg , Heidelberg 69120, Germany"},{"name":"German Centre for Cardiovascular Research (DZHK), Partner Site Heidelberg\/Mannheim , Heidelberg 69120, Germany"}]},{"given":"Isabel S","family":"Naarmann-de Vries","sequence":"additional","affiliation":[{"name":"Section of Bioinformatics and Systems Cardiology, Klaus Tschira Institute for Integrative Computational Cardiology, University Hospital Heidelberg , Heidelberg 69120, Germany"},{"name":"Department of Internal Medicine III (Cardiology, Angiology, and Pneumology), University Hospital Heidelberg , Heidelberg 69120, Germany"},{"name":"German Centre for Cardiovascular Research (DZHK), Partner Site Heidelberg\/Mannheim , Heidelberg 69120, Germany"}]},{"given":"Christoph","family":"Dieterich","sequence":"additional","affiliation":[{"name":"Section of Bioinformatics and Systems Cardiology, Klaus Tschira Institute for Integrative Computational Cardiology, University Hospital Heidelberg , Heidelberg 69120, Germany"},{"name":"Department of Internal Medicine III (Cardiology, Angiology, and Pneumology), University Hospital Heidelberg , Heidelberg 69120, Germany"},{"name":"German Centre for Cardiovascular Research (DZHK), Partner Site Heidelberg\/Mannheim , Heidelberg 69120, Germany"}]}],"member":"286","published-online":{"date-parts":[[2023,6,30]]},"reference":[{"key":"2023063008154951800_btad224-B1","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1038\/ng.3593","article-title":"Functional characterization of somatic mutations in cancer using network-based inference of protein activity","volume":"48","author":"Alvarez","year":"2016","journal-title":"Nat Genet"},{"key":"2023063008154951800_btad224-B2","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/75556","article-title":"Gene ontology: tool for the unification of biology. 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