{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T03:19:52Z","timestamp":1767928792191,"version":"3.49.0"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T00:00:00Z","timestamp":1766448000000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union\u2019s Horizon 2020","award":["859962"],"award-info":[{"award-number":["859962"]}]},{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","award":["2417\/20"],"award-info":[{"award-number":["2417\/20"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","award":["1692\/24"],"award-info":[{"award-number":["1692\/24"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Human Frontiers Science Project and the Minerva Science Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Motivation<\/jats:title>\n                    <jats:p>Protein\u2013protein interactions (PPIs) provide the skeleton for signaling pathways in the cell. Their experimental measurement, however, reveals only the existence of an interaction without any information on its functional roles. A key step in developing a working logical model of cell signaling is annotating activation\/repression (sign) of an interaction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Here, we develop SIGN Annotation aLgorithm (SIGNAL), a method for annotating PPI networks with signs based on cause-effect data. The approach is based on a multiplicative model in which the effect of a pathway is assumed to be the product of the signs along its edges. The algorithm uses network propagation techniques to quantify the influence of each edge on gene expression changes, and the resulting features are fed to a classifier for sign prediction. We validate our method using known annotations and demonstrate the utility of SIGNAL for predicting the effect of a knockout on gene expression and on telomere length.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>SIGNAL code is available at https:\/\/github.com\/L-F-S\/PPI_Network_Signer.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btaf674","type":"journal-article","created":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T02:19:43Z","timestamp":1766456383000},"source":"Crossref","is-referenced-by-count":0,"title":["Signing protein\u2013protein interaction networks"],"prefix":"10.1093","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9727-1987","authenticated-orcid":false,"given":"Lorenzo Federico","family":"Signorini","sequence":"first","affiliation":[{"name":"Blavatnik School of Computer Science and AI, Tel Aviv University , Tel Aviv 6997801,","place":["Israel"]},{"name":"Schmunis School of Biomedicine and Cancer Research, Tel Aviv University , Tel Aviv 6997801,","place":["Israel"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7934-3342","authenticated-orcid":false,"given":"Martin","family":"Kupiec","sequence":"additional","affiliation":[{"name":"Schmunis School of Biomedicine and Cancer Research, Tel Aviv University , Tel Aviv 6997801,","place":["Israel"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8363-4882","authenticated-orcid":false,"given":"Roded","family":"Sharan","sequence":"additional","affiliation":[{"name":"Blavatnik School of Computer Science and AI, Tel Aviv University , Tel Aviv 6997801,","place":["Israel"]}]}],"member":"286","published-online":{"date-parts":[[2025,12,22]]},"reference":[{"key":"2026010807465569700_btaf674-B1","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.ymeth.2012.12.001","article-title":"A comparison and optimization of yeast 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