{"doi":"10.1093/neuonc/noab227","title":"Impact of the methylation classifier and ancillary methods on CNS tumor diagnostics","abstract":"BACKGROUND: Accurate CNS tumor diagnosis can be challenging, and methylation profiling can serve as an adjunct to classify diagnostically difficult cases. METHODS: An integrated diagnostic approach was employed for a consecutive series of 1258 surgical neuropathology samples obtained primarily in a consultation practice over 2-year period. DNA methylation profiling and classification using the DKFZ/Heidelberg CNS tumor classifier was performed, as well as unsupervised analyses of methylation data. Ancillary testing, where relevant, was performed. RESULTS: Among the received cases in consultation, a high-confidence methylation classifier score (>0.84) was reached in 66.4% of cases. The classifier impacted the diagnosis in 46.7% of these high-confidence classifier score cases, including a substantially new diagnosis in 26.9% cases. Among the 289 cases received with only a descriptive diagnosis, methylation was able to resolve approximately half (144, 49.8%) with high-confidence scores. Additional methods were able to resolve diagnostic uncertainty in 41.6% of the low-score cases. Tumor purity was significantly associated with classifier score (P = 1.15e-11). Deconvolution demonstrated that suspected glioblastomas (GBMs) matching as control/inflammatory brain tissue could be resolved into GBM methylation profiles, which provided a proof-of-concept approach to resolve tumor classification in the setting of low tumor purity. CONCLUSIONS: This work assesses the impact of a methylation classifier and additional methods in a consultative practice by defining the proportions with concordant vs change in diagnosis in a set of diagnostically challenging CNS tumors. We address approaches to low-confidence scores and confounding issues of low tumor purity.","journal":"Neuro-Oncology","year":2021,"id":149422,"datarank":0.7037021823343717,"base_score":4.6913478822291435,"endowment":4.6913478822291435,"self_citation_contribution":0.7037021823343717,"citation_network_contribution":0.0,"self_endowment_contribution":0.7037021823343717,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":108,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8828,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":240507,"name":"Zied Abdullaev","orcid":"0000-0001-6345-2088","position":1,"is_corresponding":false},{"id":238039,"name":"Drew Pratt","orcid":"0000-0003-3583-8308","position":2,"is_corresponding":false},{"id":312947,"name":"Hye‐Jung Chung","orcid":null,"position":3,"is_corresponding":false},{"id":319232,"name":"Shannon Skarshaug","orcid":null,"position":4,"is_corresponding":false},{"id":635888,"name":"Valerie Zgonc","orcid":"0009-0000-6186-9998","position":5,"is_corresponding":false},{"id":239246,"name":"Candice Perry","orcid":null,"position":6,"is_corresponding":false},{"id":250439,"name":"Svetlana Pack","orcid":"0000-0003-3256-6626","position":7,"is_corresponding":false},{"id":637114,"name":"Lola Saidkhodjaeva","orcid":null,"position":8,"is_corresponding":false},{"id":292542,"name":"Sushma Nagaraj","orcid":"0000-0001-5166-1309","position":9,"is_corresponding":false},{"id":635889,"name":"Manoj Tyagi","orcid":"0009-0002-8087-0542","position":10,"is_corresponding":false},{"id":510888,"name":"Vineela Gangalapudi","orcid":null,"position":11,"is_corresponding":false},{"id":427980,"name":"Kristin Valdez","orcid":"0000-0002-1587-702X","position":12,"is_corresponding":false},{"id":637115,"name":"Rust Turakulov","orcid":null,"position":13,"is_corresponding":false},{"id":232024,"name":"Liqiang Xi","orcid":"0000-0001-5033-7072","position":14,"is_corresponding":false},{"id":232025,"name":"Mark Raffeld","orcid":"0000-0002-4039-6957","position":15,"is_corresponding":false},{"id":311195,"name":"Antonios Papanicolau‐Sengos","orcid":"0009-0008-9276-7052","position":16,"is_corresponding":false},{"id":637116,"name":"Kayla O’Donnell","orcid":null,"position":17,"is_corresponding":false},{"id":637117,"name":"Michael Newford","orcid":null,"position":18,"is_corresponding":false},{"id":109755,"name":"Mark R. 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