{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T22:59:27Z","timestamp":1790290767677,"version":"4.1.0"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Osteosarcopenia reflects the co-occurrence of osteoporosis and sarcopenia, but the molecular processes shared between impaired bone and muscle homeostasis remain incompletely characterized. This study applied a transparent, hypothesis-generating annotation-based framework to prioritize candidate genes at the osteoporosis\u2013sarcopenia interface.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      GOReverseLookup was applied to manually curated Gene Ontology term sets representing biological mechanisms relevant to osteoporosis and sarcopenia. A curated set of 367 GO terms representing key disease mechanisms served as input. Using Fisher\u2019s exact testing with Benjamini\u2013Hochberg correction and predefined ortholog-propagation settings incorporating\n                      <jats:italic>H. sapiens<\/jats:italic>\n                      ,\n                      <jats:italic>M. musculus<\/jats:italic>\n                      ,\n                      <jats:italic>R. norvegicus<\/jats:italic>\n                      ,\n                      <jats:italic>D. rerio<\/jats:italic>\n                      , and\n                      <jats:italic>X. tropicalis<\/jats:italic>\n                      annotations, the pipeline prioritized genes meeting the significance criterion for both curated states of interest. Prioritized candidates were subsequently contextualized using targeted literature assessment, DisGeNET disease-association scores, Expression Atlas tissue-expression data and KEGG pathway analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The primary analysis identified 37 candidate genes meeting the predefined significance criterion for both osteoporosis- and sarcopenia-related states of interest. The analysis highlighted a subset of less-characterized candidates, including\n                      <jats:italic>RBCK1<\/jats:italic>\n                      ,\n                      <jats:italic>LGALS9<\/jats:italic>\n                      ,\n                      <jats:italic>ZBTB7A<\/jats:italic>\n                      and\n                      <jats:italic>RPS3<\/jats:italic>\n                      , with detectable expression in the selected bone- and muscle-related tissue datasets. Recovery of previously described mediators of bone and muscle biology, including\n                      <jats:italic>TNFSF11<\/jats:italic>\n                      and\n                      <jats:italic>STAT3<\/jats:italic>\n                      , supported the biological plausibility of the prioritization framework. Pathway characterization predominantly indicated inflammatory and innate immune signalling, regulated cell death and osteoclast-related processes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>GOReverseLookup generated a transparent, annotation-based candidate list for investigating shared osteoporosis- and sarcopenia-related mechanisms. These findings should be interpreted as hypothesis-generating prioritization results requiring independent experimental and clinical validation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fgene.2026.1760184","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T22:10:13Z","timestamp":1790287813000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Bridging bone and muscle: ontology-driven prioritization of candidate genes at the osteoporosis\u2013sarcopenia interface by gene ontology reverse lookup"],"prefix":"10.3389","volume":"17","author":[{"given":"Simon","family":"\u017detko","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Vukoli\u0107","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aljo\u0161a","family":"\u0160korjanc","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir","family":"Smrkolj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nejc","family":"Umek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"i901","DOI":"10.1093\/bioinformatics\/bty559","article-title":"Semantic disease gene embeddings (SmuDGE): phenotype-based disease gene prioritization without phenotypes","volume":"34","author":"Alshahrani","year":"2018","journal-title":"Bioinformatics"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1171850","DOI":"10.3389\/fragi.2023.1171850","article-title":"Does the blunted stimulation of skeletal muscle protein synthesis by aging in response to mechanical load result from impaired ribosome biogenesis?","volume":"4","author":"Chaillou","year":"2023","journal-title":"Front. 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