{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T13:31:29Z","timestamp":1777901489713,"version":"3.51.4"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T00:00:00Z","timestamp":1748304000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Kentucky Pediatric Cancer Research Trust Fund"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>While DNA methylation signatures are distinct across nervous system neoplasms, it has not been comprehensively demonstrated whether transcriptomic signatures exhibit similar uniqueness. Additionally, no large-scale dataset for comparative gene expression analyses exists. This study addresses these knowledge and resource gaps.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We compiled and harmonized raw transcriptomic and clinical data for neoplastic (n\u2005=\u20055,402) and nonneoplastic (n\u2005=\u20051,973) nervous system samples from publicly available sources, all profiled on the same microarray platform. After adjusting for surrogate variable effects (\u201cbatch effects\u201d), machine learning methods were used to visualize, cluster, and reclassify samples with uncertain diagnoses (n\u2005=\u20052,225).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We generated the largest clinically annotated transcriptomic atlas of nervous system tumors to date. Sample clustering was primarily driven by diagnosis. We show the utility of the atlas by refining the transcriptional subtypes of pheochromocytoma and paraganglioma (PH\/PG), revealing 6 robust subtypes (Neuronal, Vascular, Metabolic, Steroidal, Developmental, Indeterminate), which were independently validated using TCGA RNA-seq data and that correlated with specific mutational signatures and clinical behaviors of these tumors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Like bulk DNA methylation, we demonstrate that bulk transcriptomic signatures are distinct across the diagnostic spectrum of nervous system neoplasms. Our atlas\u2019 broad coverage of diagnoses, including rarely studied entities, spans all ages and includes individuals from diverse geographical regions, enhancing its utility for comprehensive and robust comparative gene expression analyses, as exemplified by our PH\/PG analyses. For access, visit http:\/\/kdph.shinyapps.io\/atlas\/ or https:\/\/github.com\/axitamm\/BrainTumorAtlas.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/neuonc\/noaf130","type":"journal-article","created":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T08:53:22Z","timestamp":1747817602000},"page":"2605-2616","source":"Crossref","is-referenced-by-count":2,"title":["A clinically annotated transcriptomic atlas of nervous system tumors"],"prefix":"10.1093","volume":"27","author":[{"given":"Chi H","family":"Le","sequence":"first","affiliation":[{"name":"School of Medicine, Vanderbilt University , Nashville, Tennessee"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ajai K","family":"Nelson","sequence":"additional","affiliation":[{"name":"Oberlin College , Oberlin, Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam J","family":"Berrones","sequence":"additional","affiliation":[{"name":"Division of Prevention and Quality Improvement, Kentucky Department for Public Health , Frankfort, Kentucky"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janki R","family":"Naidugari","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Louisville , Louisville, Kentucky"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert P","family":"Naftel","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Vanderbilt University Medical Center , Nashville, Tennessee"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eyas M","family":"Hattab","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Louisville , Louisville, Kentucky"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian J","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, University of Louisville , Louisville, 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