{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T06:24:30Z","timestamp":1772173470537,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1012953","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T00:00:00Z","timestamp":1745884800000}}],"reference-count":58,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T00:00:00Z","timestamp":1744848000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["NSF FAIN-2133740"],"award-info":[{"award-number":["NSF FAIN-2133740"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000121","name":"Division of Mathematical Sciences","doi-asserted-by":"publisher","award":["CAREER DMS-2141865"],"award-info":[{"award-number":["CAREER DMS-2141865"]}],"id":[{"id":"10.13039\/100000121","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["NIH 1R01AI123659-01A1"],"award-info":[{"award-number":["NIH 1R01AI123659-01A1"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"name":"HHMI Early Career Scientist Funding"},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["NIH 1R35GM142891-01"],"award-info":[{"award-number":["NIH 1R35GM142891-01"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>\n                    Studying the mechanisms underlying the genotype-phenotype association is crucial in genetics. Gene expression studies have deepened our understanding of the genotype \u00a0\u2192\u00a0 expression \u00a0\u2192\u00a0 phenotype mechanisms. However, traditional expression quantitative trait loci (eQTL) methods often overlook the critical role of gene co-expression networks in translating genotype into phenotype. This gap highlights the need for more powerful statistical methods to analyze genotype \u00a0\u2192\u00a0 network \u00a0\u2192\u00a0 phenotype mechanism. Here, we develop a network-based method, called spectral network quantitative trait loci analysis (snQTL), to map quantitative trait loci affecting gene co-expression networks. Our approach tests the association between genotypes and joint differential networks of gene co-expression via a tensor-based spectral statistics, thereby overcoming the ubiquitous multiple testing challenges in existing methods. We demonstrate the effectiveness of snQTL in the analysis of three-spined stickleback (\n                    <jats:italic>Gasterosteus aculeatus<\/jats:italic>\n                    ) data. Compared to conventional methods, our method snQTL uncovers chromosomal regions affecting gene co-expression networks, including one strong candidate gene that would have been missed by traditional eQTL analyses. Our framework suggests the limitation of current approaches and offers a powerful network-based tool for functional loci discoveries.\n                  <\/jats:p>","DOI":"10.1371\/journal.pcbi.1012953","type":"journal-article","created":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T13:36:49Z","timestamp":1744897009000},"page":"e1012953","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["A spectral framework to map QTLs affecting joint differential networks of gene co-expression"],"prefix":"10.1371","volume":"21","author":[{"given":"Jiaxin","family":"Hu","sequence":"first","affiliation":[]},{"given":"Jesse N.","family":"Weber","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0197-7326","authenticated-orcid":true,"given":"Lauren E.","family":"Fuess","sequence":"additional","affiliation":[]},{"given":"Natalie 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