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Biol."],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>In network biology researchers generate biomolecular networks with candidate genes or proteins experimentally\u2010derived from high\u2010throughput data and known biomolecular associations. Current bioinformatics research focuses on characterizing candidate genes\/proteins, or nodes, with network characteristics, <jats:italic>e.g.<\/jats:italic>, betweenness centrality. However, there have been few research reports to characterize and prioritize biomolecular associations (\u201cedges\u201d), which can represent gene regulatory events essential to biological processes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>We developed Weighted In\u2010Path Edge Ranking (WIPER), a new computational algorithm which can help evaluate all biomolecular interactions\/associations (\u201cedges\u201d) in a network model and generate a rank order of every edge based on their in\u2010path traversal scores and statistical significance test result. To validate whether WIPER worked as we designed, we tested the algorithm on synthetic network models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our results showed WIPER can reliably discover both critical \u201cwell traversed in\u2010path edges\u201d, which are statistically more traversed than normal edges, and \u201cperipheral in\u2010path edges\u201d, which are less traversed than normal edges. Compared with other simple measures such as betweenness centrality, WIPER provides better biological interpretations. In the case study of analyzing postanal pig hearts gene expression, WIPER highlighted new signaling pathways suggestive of cardiomyocyte regeneration and proliferation. In the case study of Alzheimer\u2019s disease genetic disorder association, WIPER reports SRC:APP, AR:APP, APP:FYN, and APP:NES edges (gene\u2010gene associations) both statistically and biologically important from PubMed co\u2010citation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We believe that WIPER will become an essential software tool to help biologists discover and validate essential signaling\/regulatory events from high\u2010throughput biology data in the context of biological networks.<\/jats:p><\/jats:sec><jats:sec><jats:title>Availability<\/jats:title><jats:p>The free WIPER API is described at <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/discovery.informatics.uab.edu\/wiper\/\">discovery.informatics.uab.edu\/wiper\/<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1007\/s40484-019-0180-y","type":"journal-article","created":{"date-parts":[[2019,11,12]],"date-time":"2019-11-12T07:03:11Z","timestamp":1573542191000},"page":"313-326","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["WIPER: Weighted in\u2010Path Edge Ranking for biomolecular association networks"],"prefix":"10.1002","volume":"7","author":[{"given":"Zongliang","family":"Yue","sequence":"first","affiliation":[{"name":"<!--1--> Informatics Institute School of Medicine University of Alabama Birmingham AL 35233 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thanh","family":"Nguyen","sequence":"additional","affiliation":[{"name":"<!--1--> Informatics Institute School of Medicine University of Alabama Birmingham AL 35233 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"Zhang","sequence":"additional","affiliation":[{"name":"<!--2--> Department of Biomedical Engineering University of Alabama Birmingham AL 35233 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianyi","family":"Zhang","sequence":"additional","affiliation":[{"name":"<!--2--> Department of Biomedical Engineering University of Alabama Birmingham AL 35233 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jake Y.","family":"Chen","sequence":"additional","affiliation":[{"name":"<!--1--> Informatics Institute School of Medicine University of Alabama Birmingham AL 35233 USA"},{"name":"<!--2--> Department of Biomedical Engineering University of Alabama Birmingham AL 35233 USA"},{"name":"<!--3--> Department of Computer Science University of Alabama Birmingham AL 35233 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,12]]},"reference":[{"key":"e_1_2_8_2_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1000807"},{"key":"e_1_2_8_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep45380"},{"key":"e_1_2_8_4_2","doi-asserted-by":"publisher","DOI":"10.1684\/ecn.2013.0336"},{"key":"e_1_2_8_5_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059\u2010015\u20100808\u20109"},{"key":"e_1_2_8_6_2","doi-asserted-by":"publisher","DOI":"10.1186\/1752\u20100509\u20103\u201036"},{"key":"e_1_2_8_7_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12859\u2010016\u20101317\u2010x"},{"key":"e_1_2_8_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3244"},{"key":"e_1_2_8_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/bfgp\/els030"},{"key":"e_1_2_8_10_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471\u20102164\u201015\u2010S12\u2010S7"},{"key":"e_1_2_8_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/bies.20284"},{"key":"e_1_2_8_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2013.04.007"},{"key":"e_1_2_8_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2015.07.001"},{"key":"e_1_2_8_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1902"},{"key":"e_1_2_8_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.02.013"},{"key":"e_1_2_8_16_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13104\u2010017\u20102607\u20108"},{"key":"e_1_2_8_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep15141"},{"key":"e_1_2_8_18_2","first-page":"1070","article-title":"Identification of essential proteins based on edge clustering coefficient. 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