{"entity": "researcher", "timestamp": "2026-08-20T20:37:00.667Z", "family": "Krali", "given": "Olga", "initials": "O", "orcid": "0000-0002-6436-9531", "affiliations": ["Department of Medical Sciences, Molecular Precision Medicine, Uppsala University, Uppsala, Sweden.", "Science for Life Laboratory, Uppsala University, Uppsala, Sweden."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/fb87d31e473040cbbea724418969cae1.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/fb87d31e473040cbbea724418969cae1"}}, "publications": [{"entity": "publication", "iuid": "700c9c9b77f947918df55a48e36934ae", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/700c9c9b77f947918df55a48e36934ae.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/700c9c9b77f947918df55a48e36934ae"}}, "title": "Fluctuating DNA methylation tracks cancer evolution at clinical scale.", "authors": [{"family": "Gabbutt", "given": "Calum", "initials": "C", "orcid": "0000-0003-1946-4780", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/48f547a4c7484325a311da6e553a0247.json"}}, {"family": "Duran-Ferrer", "given": "Mart\u00ed", "initials": "M", "orcid": "0000-0003-1666-5819", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/bf156c05415b4ca68ef16154910405e8.json"}}, {"family": "Grant", "given": "Heather E", "initials": "HE", "orcid": "0000-0001-9500-1644", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/06744ddc44d748f1894b065419de8ad0.json"}}, {"family": "Mallo", "given": "Diego", "initials": "D", "orcid": "0000-0002-9046-8859", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5d97634551f74da2b29a56142551a8c2.json"}}, {"family": "Nadeu", "given": "Ferran", "initials": "F", "orcid": "0000-0003-2910-9440", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/50c437deb106439282f36834216b320a.json"}}, {"family": "Househam", "given": "Jacob", "initials": "J", "orcid": "0000-0003-3199-336X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/21e8fbb71de94c00862397e105da9408.json"}}, {"family": "Villamor", "given": "Neus", "initials": "N", "orcid": "0000-0001-6538-4111", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8fd7ec1d572b4b7b9998008a868ed898.json"}}, {"family": "M\u00fcller", "given": "Madlen", "initials": "M", "orcid": "0000-0002-1381-7517", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d8b297dc31b34418acf97fd4daec1fb3.json"}}, {"family": "Heath", "given": "Simon", "initials": "S"}, {"family": "Raineri", "given": "Emanuele", "initials": "E"}, {"family": "Krali", "given": "Olga", "initials": "O", "orcid": "0000-0002-6436-9531", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fb87d31e473040cbbea724418969cae1.json"}}, {"family": "Nordlund", "given": "Jessica", "initials": "J", "orcid": "0000-0001-8699-9959", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/27ee07e408e24eefa23105dcc6aa252b.json"}}, {"family": "Zenz", "given": "Thorsten", "initials": "T", "orcid": "0000-0001-7890-9845", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/13160825496147c897b8d57be3a61caa.json"}}, {"family": "Gut", "given": "Ivo G", "initials": "IG", "orcid": "0000-0001-7219-632X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/30b9984db1b749e2967f28dc9b631c20.json"}}, {"family": "Campo", "given": "Elias", "initials": "E", "orcid": "0000-0001-9850-9793", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/027ab2ad72e7442da10e441a24100503.json"}}, {"family": "Lopez-Guillermo", "given": "Armando", "initials": "A"}, {"family": "Fitzgibbon", "given": "Jude", "initials": "J"}, {"family": "Barnes", "given": "Chris P", "initials": "CP", "orcid": "0000-0002-9459-1395", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e1368b46b87f4bf8a3aa1aceeb6be67c.json"}}, {"family": "Shibata", "given": "Darryl", "initials": "D", "orcid": "0000-0002-4567-1639", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/87bcf54a472b47c18161607a2e4acba1.json"}}, {"family": "Martin-Subero", "given": "Jos\u00e9 I", "initials": "JI", "orcid": "0000-0001-8809-5195", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d6b1944a98214848b864342473012567.json"}}, {"family": "Graham", "given": "Trevor A", "initials": "TA", "orcid": "0000-0001-9582-1597", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/01095c73ab804c6b8a3d777973a84e86.json"}}], "type": "journal article", "published": "2025-09-00", "journal": {"title": "Nature", "issn": "1476-4687", "volume": "645", "issue": "8081", "pages": "764-773", "issn-l": "0028-0836"}, "abstract": "Cancer development and response to treatment are evolutionary processes1,2, but characterizing evolutionary dynamics at a clinically meaningful scale has remained challenging3. Here we develop a new methodology called EVOFLUx, based on natural DNA methylation barcodes fluctuating over time4, that quantitatively infers evolutionary dynamics using only a bulk tumour methylation profile as input. We apply EVOFLUx to 1,976 well-characterized lymphoid cancer samples spanning a broad spectrum of diseases and show that initial tumour growth rate, malignancy age and epimutation rates vary by orders of magnitude across disease types. We measure that subclonal selection occurs only infrequently within bulk samples and detect occasional examples of multiple independent primary tumours. Clinically, we observe faster initial tumour growth in more aggressive disease subtypes, and that evolutionary histories are strong independent prognostic factors in two series of chronic lymphocytic leukaemia. Using EVOFLUx for phylogenetic analyses of aggressive Richter-transformed chronic lymphocytic leukaemia samples detected that the seed of the transformed clone existed decades before presentation. Orthogonal verification of EVOFLUx inferences is provided using additional genetic data, including long-read nanopore sequencing, and clinical variables. Collectively, we show how widely available, low-cost bulk DNA methylation data precisely measure cancer evolutionary dynamics, and provides new insights into cancer biology and clinical behaviour.", "doi": "10.1038/s41586-025-09374-4", "pmid": "40931062", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC12443617"}, {"db": "pii", "key": "10.1038/s41586-025-09374-4"}], "notes": [], "created": "2026-08-20T08:59:16.174Z", "modified": "2026-08-20T08:59:16.679Z"}, {"entity": "publication", "iuid": "705ba9154f1a4680bbcd7210952800be", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/705ba9154f1a4680bbcd7210952800be.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/705ba9154f1a4680bbcd7210952800be"}}, "title": "Epigenomic diagnosis and prognosis of Acute Myeloid Leukemia.", "authors": [{"family": "Marchi", "given": "Francisco", "initials": "F", "orcid": "0000-0002-7318-9137", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/482d04b37fa3430fa20cc5c0606f8d5e.json"}}, {"family": "Shastri", "given": "Vivek M", "initials": "VM", "orcid": "0009-0003-1105-1575", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/967fb74480f247f182355737dbd09c46.json"}}, {"family": "Marrero", "given": "Richard J", "initials": "RJ", "orcid": "0000-0002-0789-1075", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ec63a51ed368403c945eba4e574f4019.json"}}, {"family": "Nguyen", "given": "Nam H K", "initials": "NHK", "orcid": "0000-0003-3036-4748", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/532f263d6a4f4d0592cb11b9b7d3ef8f.json"}}, {"family": "\u00d6ttl", "given": "Antonella", "initials": "A"}, {"family": "Schade", "given": "Ann-Kathrin", "initials": "AK"}, {"family": "Landwehr", "given": "Marieke", "initials": "M"}, {"family": "Krali", "given": "Olga", "initials": "O", "orcid": "0000-0002-6436-9531", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fb87d31e473040cbbea724418969cae1.json"}}, {"family": "Nordlund", "given": "Jessica", "initials": "J", "orcid": "0000-0001-8699-9959", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/27ee07e408e24eefa23105dcc6aa252b.json"}}, {"family": "Ghavami", "given": "Matin", "initials": "M"}, {"family": "Sckaff", "given": "Fernando", "initials": "F"}, {"family": "Mansinghka", "given": "Vikash K", "initials": "VK"}, {"family": "Cao", "given": "Xueyuan", "initials": "X", "orcid": "0000-0002-4396-7460", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/63ee0d1fe7554292931c57c05b2ba7a7.json"}}, {"family": "Slayton", "given": "William", "initials": "W"}, {"family": "Starostik", "given": "Petr", "initials": "P"}, {"family": "Cogle", "given": "Christopher R", "initials": "CR"}, {"family": "Ribeiro", "given": "Raul C", "initials": "RC", "orcid": "0000-0002-9956-5647", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/39feddd58f1c48e2a2edb0fef9de0857.json"}}, {"family": "Rubnitz", "given": "Jeffrey E", "initials": "JE"}, {"family": "Klco", "given": "Jeffery", "initials": "J", "orcid": "0000-0003-2961-6960", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1080ea91ed954ef6b675a8454acaacba.json"}}, {"family": "Elsayed", "given": "Abdelrahman", "initials": "A"}, {"family": "Gamis", "given": "Alan S", "initials": "AS"}, {"family": "Triche", "given": "Timothy J", "initials": "TJ", "orcid": "0000-0001-5665-946X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f9aca9faeead4e7abd3ea862f144bd33.json"}}, {"family": "Ries", "given": "Rhonda", "initials": "R", "orcid": "0000-0002-3702-7923", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/533e8f7c60bb4306b700ce9a11b6a06b.json"}}, {"family": "Kolb", "given": "E Anders", "initials": "EA"}, {"family": "Aplenc", "given": "Richard", "initials": "R"}, {"family": "Alonzo", "given": "Todd", "initials": "T"}, {"family": "Pounds", "given": "Stanley", "initials": "S", "orcid": "0000-0002-9167-2114", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/dd8e91d501684f3aada6540f0f7d4ca1.json"}}, {"family": "Meshinchi", "given": "Soheil", "initials": "S", "orcid": "0000-0002-6276-4423", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/987f1fd56b1b45c4b261d13cb669367e.json"}}, {"family": "Lamba", "given": "Jatinder K", "initials": "JK", "orcid": "0000-0003-0411-0007", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e6337ec0a97643128c5a8cd992c5c42a.json"}}], "type": "journal article", "published": "2025-07-29", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "16", "issue": "1", "pages": "6961", "issn-l": "2041-1723"}, "abstract": "Despite the critical role of DNA methylation, clinical implementations harnessing its promise have not been described in acute myeloid leukemia. Utilizing DNA methylation from 3314 leukemia patient samples across 11 harmonized cohorts, we describe the Acute Leukemia Methylome Atlas, which includes robust models capable of accurately predicting AML subtypes. A genome-wide prognostic model as well as a targeted panel of 38 CpGs significantly predict five-year survival in our pediatric and adult test cohorts. To accelerate rapid clinical utility, we develop a specimen-to-result protocol that uses long-read nanopore sequencing and machine learning to characterize patients' whole genomes and epigenomes. Clinical validation on patient samples confirms high concordance between epigenomic signatures and genomic lesions, though uniquely rare karyotypes remained challenging due to limited available training data. These results unveil the potential for increased affordability, speed, and accuracy for patients in need of complex molecular diagnosis and prognosis.", "doi": "10.1038/s41467-025-62005-4", "pmid": "40730747", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC12307604"}, {"db": "pii", "key": "10.1038/s41467-025-62005-4"}], "notes": [], "created": "2026-08-20T08:54:01.462Z", "modified": "2026-08-20T08:54:02.075Z"}, {"entity": "publication", "iuid": "a3d9993d5cc440d181a889f1f798fea6", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/a3d9993d5cc440d181a889f1f798fea6.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/a3d9993d5cc440d181a889f1f798fea6"}}, "title": "Error Reduction in Leukemia Machine Learning Classification With Conformal Prediction.", "authors": [{"family": "Lysenkova Wiklander", "given": "Mariya", "initials": "M", "orcid": "0000-0002-0012-2310", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5453326e6e074eb29647c56af0068603.json"}}, {"family": "Zachariah", "given": "Dave", "initials": "D", "orcid": "0000-0002-6698-0166", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/76aa850a94d44237b89940bf4d007a6e.json"}}, {"family": "Krali", "given": "Olga", "initials": "O", "orcid": "0000-0002-6436-9531", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fb87d31e473040cbbea724418969cae1.json"}}, {"family": "Nordlund", "given": "Jessica", "initials": "J", "orcid": "0000-0001-8699-9959", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/27ee07e408e24eefa23105dcc6aa252b.json"}}], "type": "journal article", "published": "2025-05-00", "journal": {"title": "JCO Clin Cancer Inform", "issn": "2473-4276", "volume": "9", "pages": "e2400324", "issn-l": null}, "abstract": "Recent advances in machine learning have led to the development of classifiers that predict molecular subtypes of acute lymphoblastic leukemia (ALL) using RNA-sequencing (RNA-seq) data. Although these models have shown promising results, they often lack robust performance guarantees. The aim of this study was three-fold: to quantify the uncertainty of these classifiers, to provide prediction sets that control the false-negative rate (FNR), and to perform implicit error reduction by transforming incorrect predictions into uncertain predictions.\n\nConformal prediction (CP) is a distribution-agnostic framework for generating statistically calibrated prediction sets whose size reflects model uncertainty. In this study, we applied an extension called conformal risk control to three RNA-seq ALL subtype classifiers. Leveraging RNA-seq data from 1,227 patient samples taken at diagnosis, we developed a multiclass conformal predictor ALLCoP, which generates statistically guaranteed FNR-controlled prediction sets.\n\nALLCoP was able to create prediction sets with specified FNR tolerances ranging from 7.5% to 30%. In a validation cohort, ALLCoP successfully reduced the FNR of the ALLIUM RNA-seq ALL subtype classifier from 8.95% to 3.5%. For patients whose subtype was not previously known, the use of ALLCoP was able to reduce the occurrence of empty predictions from 37% to 17%. Notably, up to 34% of the multiple-class prediction sets included the PAX5alt subtype, suggesting that increased prediction set size may reflect secondary aberrations and biological complexity, contributing to classifier uncertainty. Finally, ALLCoP was validated on two additional RNA-seq ALL subtype classifiers, ALLSorts and ALLCatchR.\n\nOur results highlight the potential of CP in enhancing the use of oncologic RNA-seq subtyping classifiers and also in uncovering additional molecular aberrations of potential clinical importance.", "doi": "10.1200/CCI-24-00324", "pmid": "40435436", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC12133051"}], "notes": [], "created": "2026-08-20T12:37:36.468Z", "modified": "2026-08-20T12:37:36.585Z"}, {"entity": "publication", "iuid": "c594aedb69964c36a8d5a49b11bb682c", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/c594aedb69964c36a8d5a49b11bb682c.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/c594aedb69964c36a8d5a49b11bb682c"}}, "title": "Ex Vivo Drug Responses and Molecular Profiles of 597 Pediatric Acute Lymphoblastic Leukemia Patients", "authors": [{"family": "Enblad", "given": "Anna Pia", "initials": "AP"}, {"family": "Krali", "given": "Olga", "initials": "O", "orcid": "0000-0002-6436-9531", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fb87d31e473040cbbea724418969cae1.json"}}, {"family": "Gezelius", "given": "Henrik", "initials": "H"}, {"family": "Lundmark", "given": "Anders", "initials": "A"}, {"family": "Blom", "given": "Kristin", "initials": "K"}, {"family": "Andersson", "given": "Claes", "initials": "C"}, {"family": "Palle", "given": "Josefine", "initials": "J"}, {"family": "Frost", "given": "Britt Marie", "initials": "BM"}, {"family": "Ryh\u00e4nen", "given": "Samppa", "initials": "S"}, {"family": "Fl\u00e6gstad", "given": "Trond", "initials": "T"}, {"family": "J\u00f3nsson", "given": "\u00d3lafur G", "initials": "\u00d3G"}, {"family": "Schmiegelow", "given": "Kjeld", "initials": "K"}, {"family": "Heyman", "given": "Mats", "initials": "M"}, {"family": "Harila", "given": "Arja", "initials": "A"}, {"family": "Nygren", "given": "Peter", "initials": "P"}, {"family": "Larsson", "given": "Rolf", "initials": "R"}, {"family": "L\u00f6nnerholm", "given": "Gudmar", "initials": "G"}, {"family": "Nordlund", "given": "Jessica", "initials": "J", "orcid": "0000-0001-8699-9959", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/27ee07e408e24eefa23105dcc6aa252b.json"}}], "type": "posted-content", "published": "2024-12-20", "journal": {"issn-l": null}, "abstract": null, "doi": "10.1101/2024.12.17.24319138", "pmid": null, "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T10:59:34.867Z", "modified": "2026-08-20T10:59:34.925Z"}, {"entity": "publication", "iuid": "146d1af65d564cb7b14832b3d89bf122", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/146d1af65d564cb7b14832b3d89bf122.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/146d1af65d564cb7b14832b3d89bf122"}}, "title": "Evolutionary dynamics of 1,976 lymphoid malignancies predict clinical outcome", "authors": [{"family": "Gabbutt", "given": "Calum", "initials": "C", "orcid": "0000-0003-1946-4780", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/48f547a4c7484325a311da6e553a0247.json"}}, {"family": "Duran-Ferrer", "given": "Mart\u00ed", "initials": "M", "orcid": "0000-0003-1666-5819", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/bf156c05415b4ca68ef16154910405e8.json"}}, {"family": "Grant", "given": "Heather", "initials": "H", "orcid": "0000-0001-9500-1644", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/06744ddc44d748f1894b065419de8ad0.json"}}, {"family": "Mallo", "given": "Diego", "initials": "D", "orcid": "0000-0002-9046-8859", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5d97634551f74da2b29a56142551a8c2.json"}}, {"family": "Nadeu", "given": "Ferran", "initials": "F", "orcid": 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