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Table 2_Bridging bone and muscle: ontology-driven prioritization of candidate genes at the osteoporosis–sarcopenia interface by gene ontology reverse lookup.docx Simon Žetko (25105867) Lan Vukolić (25105870) Aljoša Škorjanc (25105873) Vladimir Smrkolj (25105876) Nejc Umek (8796548) Genetics candidate gene prioritization cytosolic DNA-sensing GOReverseLookup muscle-bone crosstalk necroptosis NF-κB signaling osteosarcopenia Introduction<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–sarcopenia interface.</p>Methods<p>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’s exact testing with Benjamini–Hochberg correction and predefined ortholog-propagation settings incorporating H. sapiens, M. musculus, R. norvegicus, D. rerio, and X. tropicalis 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.</p>Results<p>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 RBCK1, LGALS9, ZBTB7A and RPS3, with detectable expression in the selected bone- and muscle-related tissue datasets. Recovery of previously described mediators of bone and muscle biology, including TNFSF11 and STAT3, supported the biological plausibility of the prioritization framework. Pathway characterization predominantly indicated inflammatory and innate immune signalling, regulated cell death and osteoclast-related processes.</p>Conclusion<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.</p> 2026-09-24T22:03:19Z Dataset Dataset 10.3389/fgene.2026.1760184.s003 https://figshare.com/articles/dataset/Table_2_Bridging_bone_and_muscle_ontology-driven_prioritization_of_candidate_genes_at_the_osteoporosis_sarcopenia_interface_by_gene_ontology_reverse_lookup_docx/33991024 CC BY 4.0