{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:53:47Z","timestamp":1792788827347,"version":"4.5.0"},"reference-count":61,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the National Research Foundation of Korea","award":["RS-2023-00220894"],"award-info":[{"award-number":["RS-2023-00220894"]}],"id":[{"id":"https:\/\/ror.org\/013aysd81","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Skeletal muscle atrophy is a critical physiological risk during long-duration spaceflight, yet candidate blood-accessible transcriptomic biomarkers for longitudinal monitoring remain unavailable. We developed an integrative multi-mission framework combining a primary discovery transcriptome from THP-1 monocytic cells exposed to International Space Station (ISS) microgravity (GEO: Sci. Adv. 2026 (\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/doi.org\/10.1126\/sciadv.adw7832\" xlink:type=\"simple\">https:\/\/doi.org\/10.1126\/sciadv.adw7832<\/jats:ext-link>\n                    , Data S1-S10); NASA OSDR: Al-Ahmadi et al. 2026; n\u2009=\u20098 spaceflight, 8 ground control) \u2014 yielding 4,522 spaceflight-differentially expressed genes (SDEGs) \u2014 with a PRISMA-compliant meta-analysis of 46 verified spaceflight studies, producing a 726-gene consensus set. Cross-referencing these datasets identified 103 intersection genes; application of our Integrated Concordance Score (ICS) nominated an 18-gene candidate biomarker panel nominated across six external missions. Orthogonal cross-tissue concordance analysis using six C2C12 myotube simulated-microgravity datasets demonstrated Pearson r\u2009=\u20090.79 (95% CI 0.52\u20130.92, p\u2009&lt;\u20090.001), with a conserved stress module achieving r\u2009=\u20090.88; complementary concordance in human primary skeletal myotubes confirmed tri-model directional concordance for 13 stress-module genes. Gold-tier biomarkers (TNNT3, TRIM63, ACTC1, IGF2; ICS\u2009\u2265\u20098.0) showed \u226583% multi-mission concordance. Temporal modelling informs a preliminary two-tier fortnightly\/monthly monitoring framework aligned with measured saturation kinetics, and the prioritised panel converges on coordinated ubiquitin-proteasome activation, AKT\u2013mTOR\u2013FOXO3a remodelling, E2F suppression, and sarcomeric reprogramming. Integrated drug\u2013gene analysis identified bimagrumab combined with leucine as the top predicted prioritised countermeasure pair (computational Bliss\u2009=\u20092.8). These findings establish a proposed candidate blood-accessible biomarker framework for periodic muscle health surveillance during long-duration human spaceflight, available prospective validation in astronaut blood samples. The unit of analysis was the analytical contrast (spaceflight vs. matched ground control), not the publication. Cross-platform harmonization was performed via gene-level mapping and rank-based normalization.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0358130","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T17:23:21Z","timestamp":1791393801000},"page":"e0358130","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrative transcriptomics identifies an 18-gene candidate blood-accessible biomarker panel for longitudinal monitoring of spaceflight-induced muscle atrophy"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9861-6521","authenticated-orcid":true,"given":"Jae Ho","family":"Shim","sequence":"first","affiliation":[{"name":"Korea University College of Medicine","place":["Seoul, Republic of Korea"],"department":["Department of Anatomy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Yeon","family":"Lee","sequence":"additional","affiliation":[{"name":"Korea University College of Medicine","place":["Seoul, Republic of Korea"],"department":["Department of Anatomy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihye","family":"Han","sequence":"additional","affiliation":[{"name":"Korea University College of Medicine","place":["Seoul, Republic of Korea"],"department":["Department of Anatomy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeon Soo","family":"Kim","sequence":"additional","affiliation":[{"name":"Korea University College of Medicine","place":["Seoul, Republic of Korea"],"department":["Department of Anatomy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,10,7]]},"reference":[{"key":"pone.0358130.ref001","doi-asserted-by":"crossref","first-page":"3201","DOI":"10.1242\/jeb.204.18.3201","article-title":"Functional and structural adaptations of skeletal muscle to microgravity","volume":"204","author":"RH Fitts","year":"2001","journal-title":"J Exp Biol"},{"issue":"4","key":"pone.0358130.ref002","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1152\/japplphysiol.91578.2008","article-title":"Exercise in space: human skeletal muscle after 6 months aboard the International Space Station","volume":"106","author":"S Trappe","year":"2009","journal-title":"J Appl Physiol (1985)"},{"key":"pone.0358130.ref003","doi-asserted-by":"crossref","first-page":"3567","DOI":"10.1113\/jphysiol.2010.188508","article-title":"Prolonged space flight-induced alterations in the structure and function of human skeletal muscle fibres","volume":"588","author":"RH Fitts","year":"2010","journal-title":"J Physiol"},{"issue":"3","key":"pone.0358130.ref004","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1152\/japplphysiol.90558.2008","article-title":"Skeletal muscle proteolysis in response to short-term unloading in humans","volume":"105","author":"PA Tesch","year":"2008","journal-title":"J Appl Physiol (1985)"},{"key":"pone.0358130.ref005","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1113\/jphysiol.2004.062166","article-title":"Human single muscle fibre function with 84 day bed-rest and resistance exercise","volume":"557","author":"S Trappe","year":"2004","journal-title":"J Physiol"},{"key":"pone.0358130.ref006","article-title":"Canonical fast-twitch MYH4 expression in microgravity","author":"EA Kharlamova","year":"2023","journal-title":"Sci Adv"},{"key":"pone.0358130.ref007","first-page":"1","article-title":"Relationship between force and myosin heavy chain isoform composition in single human skeletal muscle fibres","volume":"108","author":"LS Krivickas","year":"2010","journal-title":"J Appl Physiol"},{"issue":"1","key":"pone.0358130.ref008","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/s41526-023-00256-5","article-title":"Effects of exercise countermeasures on multisystem function in long duration spaceflight astronauts","volume":"9","author":"JM Scott","year":"2023","journal-title":"NPJ Microgravity"},{"key":"pone.0358130.ref009","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/s41526-020-00111-x","article-title":"High intensity training during spaceflight: results from the NASA Sprint Study","volume":"6","author":"KL English","year":"2020","journal-title":"NPJ Microgravity"},{"issue":"5","key":"pone.0358130.ref010","doi-asserted-by":"crossref","DOI":"10.1152\/ajpendo.00590.2009","article-title":"Insulin resistance induced by physical inactivity is associated with multiple transcriptional changes in skeletal muscle in young men","volume":"299","author":"AC Alibegovic","year":"2010","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"pone.0358130.ref011","article-title":"Spaceflight alters expression of microRNA in human peripheral blood mononuclear cells","volume":"15","author":"CE Metzger","year":"2020","journal-title":"PLoS 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USA"},{"issue":"244","key":"pone.0358130.ref042","doi-asserted-by":"crossref","DOI":"10.1126\/stke.2442004re11","article-title":"Molecular and cellular determinants of skeletal muscle atrophy and hypertrophy","volume":"2004","author":"V Sartorelli","year":"2004","journal-title":"Sci STKE"},{"issue":"6","key":"pone.0358130.ref043","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1002\/jcb.20671","article-title":"Mechanical stimuli and nutrients regulate rapamycin-sensitive signaling through distinct mechanisms in skeletal muscle","volume":"97","author":"TA Hornberger","year":"2006","journal-title":"J Cell Biochem"},{"issue":"5","key":"pone.0358130.ref044","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1113\/expphysiol.2006.036525","article-title":"Plasticity of human skeletal muscle: gene expression to in vivo function","volume":"92","author":"SDR Harridge","year":"2007","journal-title":"Exp Physiol"},{"key":"pone.0358130.ref045","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1152\/japplphysiol.00811.2004","article-title":"Diminished overload-induced hypertrophy in aged fast-twitch skeletal muscle","volume":"98","author":"DM Thomson","year":"2006","journal-title":"J Appl Physiol"},{"key":"pone.0358130.ref046","article-title":"The UPS in diabetes and obesity","author":"SS Wing","year":"2008","journal-title":"BMC Biochem"},{"key":"pone.0358130.ref047","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.bbrc.2015.05.032","article-title":"mTOR is necessary for proper satellite cell activity and skeletal muscle regeneration","volume":"463","author":"P Zhang","year":"2015","journal-title":"Biochem Biophys Res Commun"},{"key":"pone.0358130.ref048","first-page":"3787","article-title":"Molecular adaptation during voluntary exercise","volume":"590","author":"WE Teague","year":"2012","journal-title":"J Physiol"},{"issue":"4","key":"pone.0358130.ref049","doi-asserted-by":"crossref","DOI":"10.1152\/ajpcell.00009.2019","article-title":"Integrin signaling: linking mechanical stimulation to skeletal muscle hypertrophy","volume":"317","author":"MD Boppart","year":"2019","journal-title":"Am J Physiol Cell Physiol"},{"issue":"7","key":"pone.0358130.ref050","doi-asserted-by":"crossref","DOI":"10.1152\/ajpendo.00276.2014","article-title":"Metabolic and hormonal responses to isoenergetic high-intensity interval exercise and continuous moderate-intensity exercise","volume":"307","author":"JM Peake","year":"2014","journal-title":"Am J Physiol Endocrinol Metab"},{"issue":"1","key":"pone.0358130.ref051","first-page":"30","article-title":"Regulation of ribosome biogenesis in skeletal muscle hypertrophy","volume":"34","author":"VC Figueiredo","year":"2019","journal-title":"Physiology (Bethesda)"},{"key":"pone.0358130.ref052","first-page":"6033","article-title":"Understanding muscle atrophy: a matter of cell signalling","volume":"26","author":"D Coletti","year":"2016","journal-title":"Eur J Transl Myol"},{"issue":"4","key":"pone.0358130.ref053","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1083\/jcb.200105147","article-title":"Different modes of hypertrophy in skeletal muscle fibers","volume":"156","author":"AC Paul","year":"2002","journal-title":"J Cell Biol"},{"key":"pone.0358130.ref054","article-title":"Recovery from hindlimb suspension: adaptations in control and reloaded muscles","volume":"73","author":"JA Faulkner","year":"1992","journal-title":"J Appl Physiol"},{"issue":"3","key":"pone.0358130.ref055","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1152\/physrev.00033.2014","article-title":"Mechanisms regulating neuromuscular junction development and function and causes of muscle wasting","volume":"95","author":"LA Tintignac","year":"2015","journal-title":"Physiol Rev"},{"issue":"1","key":"pone.0358130.ref056","first-page":"26","article-title":"Starring or supporting role? 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