{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,22]],"date-time":"2025-02-22T00:38:28Z","timestamp":1740184708816,"version":"3.37.3"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"14","license":[{"start":{"date-parts":[[2019,7,8]],"date-time":"2019-07-08T00:00:00Z","timestamp":1562544000000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["CCF-1617678","DBI-1759858"],"award-info":[{"award-number":["CCF-1617678","DBI-1759858"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R01-GM095955"],"award-info":[{"award-number":["R01-GM095955"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>High-quality curation of the proteins and interactions in signaling pathways is slow and painstaking. As a result, many experimentally detected interactions are not annotated to any pathways. A natural question that arises is whether or not it is possible to automatically leverage existing pathway annotations to identify new interactions for inclusion in a given pathway.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We present RegLinker, an algorithm that achieves this purpose by computing multiple short paths from pathway receptors to transcription factors within a background interaction network. The key idea underlying RegLinker is the use of regular language constraints to control the number of non-pathway interactions that are present in the computed paths. We systematically evaluate RegLinker and five alternative approaches against a comprehensive set of 15 signaling pathways and demonstrate that RegLinker recovers withheld pathway proteins and interactions with the best precision and recall. We used RegLinker to propose new extensions to the pathways. We discuss the literature that supports the inclusion of these proteins in the pathways. These results show the broad potential of automated analysis to attenuate difficulties of traditional manual inquiry.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and implementation<\/jats:title>\n                  <jats:p>https:\/\/github.com\/Murali-group\/RegLinker.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Supplementary information<\/jats:title>\n                  <jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btz360","type":"journal-article","created":{"date-parts":[[2019,5,14]],"date-time":"2019-05-14T19:42:18Z","timestamp":1557862938000},"page":"i624-i633","source":"Crossref","is-referenced-by-count":6,"title":["Reconstructing signaling pathways using regular language constrained paths"],"prefix":"10.1093","volume":"35","author":[{"given":"Mitchell J","family":"Wagner","sequence":"first","affiliation":[{"name":"Department of Computer Science, Virginia Tech, Blacksburg, VA, USA"}]},{"given":"Aditya","family":"Pratapa","sequence":"additional","affiliation":[{"name":"Department of Computer Science, Virginia Tech, Blacksburg, VA, USA"}]},{"given":"T M","family":"Murali","sequence":"additional","affiliation":[{"name":"Department of Computer Science, Virginia Tech, Blacksburg, VA, USA"}]}],"member":"286","published-online":{"date-parts":[[2019,7,5]]},"reference":[{"key":"2023062712414473700_btz360-B1","doi-asserted-by":"crossref","first-page":"50.","DOI":"10.1186\/1741-7007-7-50","article-title":"Mapping the human membrane proteome: a majority of the human membrane proteins can be classified according to function and evolutionary origin","volume":"7","author":"Almen","year":"2009","journal-title":"BMC Biol"},{"key":"2023062712414473700_btz360-B2","doi-asserted-by":"crossref","first-page":"784","DOI":"10.2741\/3957","article-title":"The Wnt signaling pathways and cell adhesion","volume":"17","author":"Amin","year":"2012","journal-title":"Front. Biosci"},{"key":"2023062712414473700_btz360-B3","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1038\/nmeth.1637","article-title":"PSICQUIC and PSISCORE: accessing and scoring molecular interactions","volume":"8","author":"Aranda","year":"2011","journal-title":"Nat. Methods"},{"key":"2023062712414473700_btz360-B4","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1137\/S0097539798337716","article-title":"Formal-language-constrained path problems","volume":"30","author":"Barrett","year":"2000","journal-title":"SIAM J. Comput"},{"key":"2023062712414473700_btz360-B5","doi-asserted-by":"crossref","first-page":"545","DOI":"10.3390\/ijms18030545","article-title":"More insight into BDNF against neurodegeneration: anti-apoptosis, anti-oxidation, and suppression of autophagy","volume":"18","author":"Chen","year":"2017","journal-title":"Int. J. Mol. Sci"},{"key":"2023062712414473700_btz360-B6","doi-asserted-by":"crossref","first-page":"D481","DOI":"10.1093\/nar\/gkv1351","article-title":"The Reactome pathway Knowledgebase","volume":"44","author":"Fabregat","year":"2016","journal-title":"Nucleic Acids Res"},{"key":"2023062712414473700_btz360-B7","doi-asserted-by":"crossref","first-page":"e22.","DOI":"10.1093\/nar\/gkq1207","article-title":"Discovering pathways by orienting edges in protein interaction networks","volume":"39","author":"Gitter","year":"2011","journal-title":"Nucleic Acids Res"},{"key":"2023062712414473700_btz360-B8","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.virusres.2018.05.022","article-title":"TNF-\u03b1 exerts potent anti-rotavirus effects via the activation of classical NF-\u03baB pathway","volume":"253","author":"Hakim","year":"2018","journal-title":"Virus Res"},{"key":"2023062712414473700_btz360-B9","doi-asserted-by":"crossref","first-page":"D261","DOI":"10.1093\/nar\/gkr1122","article-title":"PhosphoSitePlus: a comprehensive resource for investigating the structure and function of experimentally determined post-translational modifications in man and mouse","volume":"40","author":"Hornbeck","year":"2012","journal-title":"Nucleic Acids Res"},{"key":"2023062712414473700_btz360-B10","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1093\/bioinformatics\/btx029","article-title":"AptRank: an adaptive PageRank model for protein function prediction on bi-relational graphs","volume":"33","author":"Jiang","year":"2017","journal-title":"Bioinformatics"},{"key":"2023062712414473700_btz360-B11","doi-asserted-by":"crossref","first-page":"R3.","DOI":"10.1186\/gb-2010-11-1-r3","article-title":"NetPath: a public resource of curated signal transduction pathways","volume":"11","author":"Kandasamy","year":"2010","journal-title":"Genome Biol"},{"key":"2023062712414473700_btz360-B12","doi-asserted-by":"crossref","first-page":"D457","DOI":"10.1093\/nar\/gkv1070","article-title":"KEGG as a reference resource for gene and protein annotation","volume":"44","author":"Kanehisa","year":"2016","journal-title":"Nucleic Acids Res"},{"key":"2023062712414473700_btz360-B13","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.tcm.2007.03.002","article-title":"Brain-derived neurotrophic factor: a newly described mediator of angiogenesis","volume":"17","author":"Kermani","year":"2007","journal-title":"Trends Cardiovasc. Med"},{"key":"2023062712414473700_btz360-B15","doi-asserted-by":"crossref","first-page":"W90","DOI":"10.1093\/nar\/gkw377","article-title":"Enrichr: a comprehensive gene set enrichment analysis web server 2016 update","volume":"44","author":"Kuleshov","year":"2016","journal-title":"Nucleic Acids Res"},{"key":"2023062712414473700_btz360-B16","doi-asserted-by":"crossref","first-page":"84.","DOI":"10.1186\/1752-0509-7-84","article-title":"Inferring the effective TOR-dependent network: a computational study in yeast","volume":"7","author":"Mohammadi","year":"2013","journal-title":"BMC Syst. Biol"},{"key":"2023062712414473700_btz360-B17","doi-asserted-by":"crossref","first-page":"e1002640.","DOI":"10.1371\/journal.pcbi.1002640","article-title":"A network-based approach for predicting missing pathway interactions","volume":"8","author":"Navlakha","year":"2012","journal-title":"PLoS Comput. Biol"},{"key":"2023062712414473700_btz360-B18","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1023\/A:1020546615229","article-title":"TNF-induced signaling in apoptosis","volume":"19","author":"Rath","year":"1999","journal-title":"J. Clin. Immunol"},{"key":"2023062712414473700_btz360-B19","doi-asserted-by":"crossref","first-page":"16002","DOI":"10.1038\/npjsba.2016.2","article-title":"Pathways on demand: automated reconstruction of human signaling networks","volume":"2","author":"Ritz","year":"2016","journal-title":"NPJ Syst. Biol. Appl"},{"key":"2023062712414473700_btz360-B20","volume-title":"Algorithms in C, Part 5: Graph Algorithms","author":"Sedgewick","year":"2001","edition":"3"},{"key":"2023062712414473700_btz360-B21","first-page":"7388","article-title":"Tumor necrosis factor alpha exerts powerful anti-influenza virus effects in lung epithelial cells","volume":"70","author":"Seo","year":"2002","journal-title":"J. Virol"},{"key":"2023062712414473700_btz360-B22","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1093\/bioinformatics\/btu043","article-title":"Network orientation via shortest paths","volume":"30","author":"Silverbush","year":"2014","journal-title":"Bioinformatics"},{"key":"2023062712414473700_btz360-B23","doi-asserted-by":"crossref","first-page":"34.","DOI":"10.1186\/1471-2105-3-34","article-title":"Automated modelling of signal transduction networks","volume":"3","author":"Steffen","year":"2002","journal-title":"BMC Bioinformatics"},{"key":"2023062712414473700_btz360-B24","doi-asserted-by":"crossref","first-page":"e21800.","DOI":"10.1371\/journal.pone.0021800","article-title":"REVIGO summarizes and visualizes long lists of gene ontology terms","volume":"6","author":"Supek","year":"2011","journal-title":"PLoS One"},{"key":"2023062712414473700_btz360-B25","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1186\/1752-0509-3-67","article-title":"BowTieBuilder: modeling signal transduction pathways","volume":"3","author":"Supper","year":"2009","journal-title":"BMC Syst. Biol"},{"key":"2023062712414473700_btz360-B26","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1016\/j.cell.2010.01.044","article-title":"An atlas of combinatorial transcriptional regulation in mouse and man","volume":"140","author":"Ravasi","year":"2010","journal-title":"Cell"},{"key":"2023062712414473700_btz360-B27","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1089\/cmb.2012.0092","article-title":"Simultaneous reconstruction of multiple signaling pathways via the prize-collecting Steiner forest problem","volume":"20","author":"Tuncbag","year":"2013","journal-title":"J. Comput. Biol"},{"key":"2023062712414473700_btz360-B28","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1038\/nrg2538","article-title":"A census of human transcription factors: function, expression and evolution","volume":"10","author":"Vaquerizas","year":"2009","journal-title":"Nat. Rev. Genet"},{"key":"2023062712414473700_btz360-B29","doi-asserted-by":"crossref","first-page":"e12881.","DOI":"10.1111\/acel.12881","article-title":"The TrkB-T1 receptor mediates BDNF-induced migration of aged cardiac microvascular endothelial cells by recruiting Willin","volume":"18","author":"Wang","year":"2019","journal-title":"Aging Cell"},{"key":"2023062712414473700_btz360-B30","doi-asserted-by":"crossref","first-page":"793.","DOI":"10.1038\/s41419-018-0818-0","article-title":"Crosstalk between hepatic tumor cells and macrophages via Wnt\/\u03b2-catenin signaling promotes M2-like macrophage polarization and reinforces tumor malignant behaviors","volume":"9","author":"Yang","year":"2018","journal-title":"Cell Death Dis"},{"key":"2023062712414473700_btz360-B31","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1038\/ng.337","article-title":"Bridging high-throughput genetic and transcriptional data reveals cellular responses to alpha-synuclein toxicity","volume":"41","author":"Yeger-Lotem","year":"2009","journal-title":"Nat. Genet"},{"key":"2023062712414473700_btz360-B32","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1287\/mnsc.17.11.712","article-title":"Finding the k shortest loopless paths in a network","volume":"17","author":"Yen","year":"1971","journal-title":"Manage. Sci"},{"key":"2023062712414473700_btz360-B33","doi-asserted-by":"crossref","first-page":"pl1.","DOI":"10.1126\/scisignal.2001935","article-title":"ANAT: a tool for constructing and analyzing functional protein networks","volume":"4","author":"Yosef","year":"2011","journal-title":"Sci. Signal"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/35\/14\/i624\/50721540\/bioinformatics_35_14_i624.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/35\/14\/i624\/50721540\/bioinformatics_35_14_i624.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,27]],"date-time":"2023-06-27T12:42:50Z","timestamp":1687869770000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/35\/14\/i624\/5529247"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7]]},"references-count":32,"journal-issue":{"issue":"14","published-print":{"date-parts":[[2019,7,15]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btz360","relation":{},"ISSN":["1367-4803","1367-4811"],"issn-type":[{"type":"print","value":"1367-4803"},{"type":"electronic","value":"1367-4811"}],"subject":[],"published-other":{"date-parts":[[2019,7]]},"published":{"date-parts":[[2019,7]]}}}