{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T03:14:07Z","timestamp":1791947647716,"version":"4.3.4"},"reference-count":110,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T00:00:00Z","timestamp":1659312000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,8,11]],"date-time":"2022-08-11T00:00:00Z","timestamp":1660176000000},"content-version":"vor","delay-in-days":10,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Med"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Richter transformation (RT) is a paradigmatic evolution of chronic lymphocytic leukemia (CLL) into a very aggressive large B cell lymphoma conferring a dismal prognosis. The mechanisms driving RT remain largely unknown. We characterized the whole genome, epigenome and transcriptome, combined with single-cell DNA\/RNA-sequencing analyses and functional experiments, of 19 cases of CLL developing RT. Studying 54 longitudinal samples covering up to 19 years of disease course, we uncovered minute subclones carrying genomic, immunogenetic and transcriptomic features of RT cells already at CLL diagnosis, which were dormant for up to 19 years before transformation. We also identified new driver alterations, discovered a new mutational signature (SBS-RT), recognized an oxidative phosphorylation (OXPHOS)\n                    <jats:sup>high<\/jats:sup>\n                    \u2013B cell receptor (BCR)\n                    <jats:sup>low<\/jats:sup>\n                    -signaling transcriptional axis in RT and showed that OXPHOS inhibition reduces the proliferation of RT cells. These findings demonstrate the early seeding of subclones driving advanced stages of cancer evolution and uncover potential therapeutic targets for RT.\n                  <\/jats:p>","DOI":"10.1038\/s41591-022-01927-8","type":"journal-article","created":{"date-parts":[[2022,8,11]],"date-time":"2022-08-11T12:50:28Z","timestamp":1660222228000},"page":"1662-1671","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":140,"title":["Detection of early seeding of Richter transformation in chronic lymphocytic leukemia"],"prefix":"10.1038","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2910-9440","authenticated-orcid":false,"given":"Ferran","family":"Nadeu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3493-0874","authenticated-orcid":false,"given":"Romina","family":"Royo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramon","family":"Massoni-Badosa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3447-3848","authenticated-orcid":false,"given":"Heribert","family":"Playa-Albinyana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"Garcia-Torre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1666-5819","authenticated-orcid":false,"given":"Mart\u00ed","family":"Duran-Ferrer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin J.","family":"Dawson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Kulis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ander","family":"Diaz-Navarro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neus","family":"Villamor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1387-6231","authenticated-orcid":false,"given":"Juan L.","family":"Melero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4910-5394","authenticated-orcid":false,"given":"Vicente","family":"Chapaprieta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2000-9718","authenticated-orcid":false,"given":"Ana","family":"Dueso-Barroso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julio","family":"Delgado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7393-1138","authenticated-orcid":false,"given":"Riccardo","family":"Moia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Ruiz-Gil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenica","family":"Marchese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariadna","family":"Gir\u00f3","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N\u00faria","family":"Verdaguer-Dot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00f3nica","family":"Romo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2588-7413","authenticated-orcid":false,"given":"Guillem","family":"Clot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Rozman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6794-6456","authenticated-orcid":false,"given":"Gerard","family":"Frigola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0385-3415","authenticated-orcid":false,"given":"Alfredo","family":"Rivas-Delgado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tycho","family":"Baumann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3819-4846","authenticated-orcid":false,"given":"Miguel","family":"Alcoceba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcos","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fina","family":"Climent","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pau","family":"Abrisqueta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5745-9996","authenticated-orcid":false,"given":"Josep","family":"Castellv\u00ed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesc","family":"Bosch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Aymerich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Enjuanes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00edlvia","family":"Ruiz-Gasp\u00e0","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armando","family":"L\u00f3pez-Guillermo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"Jares","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7192-2385","authenticated-orcid":false,"given":"S\u00edlvia","family":"Be\u00e0","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0309-604X","authenticated-orcid":false,"given":"Salvador","family":"Capella-Gutierrez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josep Ll.","family":"Gelp\u00ed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4925-8988","authenticated-orcid":false,"given":"N\u00faria","family":"L\u00f3pez-Bigas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Torrents","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3921-0510","authenticated-orcid":false,"given":"Peter J.","family":"Campbell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7219-632X","authenticated-orcid":false,"given":"Ivo","family":"Gut","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Rossi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4681-0151","authenticated-orcid":false,"given":"Gianluca","family":"Gaidano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9525-1483","authenticated-orcid":false,"given":"Xose S.","family":"Puente","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8371-2067","authenticated-orcid":false,"given":"Pablo M.","family":"Garcia-Roves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7486-8484","authenticated-orcid":false,"given":"Dolors","family":"Colomer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3276-1889","authenticated-orcid":false,"given":"Holger","family":"Heyn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5017-1620","authenticated-orcid":false,"given":"Francesco","family":"Maura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8809-5195","authenticated-orcid":false,"given":"Jos\u00e9 I.","family":"Mart\u00edn-Subero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9850-9793","authenticated-orcid":false,"given":"El\u00edas","family":"Campo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,8,11]]},"reference":[{"key":"1927_CR1","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1038\/255197a0","volume":"255","author":"J Cairns","year":"1975","unstructured":"Cairns, J. Mutation selection and the natural history of cancer. Nature 255, 197\u2013200 (1975).","journal-title":"Nature"},{"key":"1927_CR2","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1126\/science.959840","volume":"194","author":"PC Nowell","year":"1976","unstructured":"Nowell, P. C. The clonal evolution of tumor cell populations. Science 194, 23\u201328 (1976).","journal-title":"Science"},{"key":"1927_CR3","doi-asserted-by":"publisher","first-page":"2239","DOI":"10.1016\/j.cell.2021.03.009","volume":"184","author":"SC Dentro","year":"2021","unstructured":"Dentro, S. C. et al. Characterizing genetic intra-tumor heterogeneity across 2,658 human cancer genomes. Cell 184, 2239\u20132254 (2021).","journal-title":"Cell"},{"key":"1927_CR4","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1038\/s41586-019-1907-7","volume":"578","author":"M Gerstung","year":"2020","unstructured":"Gerstung, M. et al. The evolutionary history of 2,658 cancers. Nature 578, 122\u2013128 (2020).","journal-title":"Nature"},{"key":"1927_CR5","doi-asserted-by":"publisher","first-page":"1135","DOI":"10.1038\/nm.4410","volume":"23","author":"AA Ferrando","year":"2017","unstructured":"Ferrando, A. A. & L\u00f3pez-Ot\u00edn, C. Clonal evolution in leukemia. Nat. Med. 23, 1135\u20131145 (2017).","journal-title":"Nat. Med."},{"key":"1927_CR6","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1182\/asheducation-2018.1.256","volume":"2018","author":"W Ding","year":"2018","unstructured":"Ding, W. Richter transformation in the era of novel agents. Hematology 2018, 256\u2013263 (2018).","journal-title":"Hematology"},{"key":"1927_CR7","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1001\/jamaoncol.2014.218","volume":"1","author":"KJ Maddocks","year":"2015","unstructured":"Maddocks, K. J. et al. Etiology of ibrutinib therapy discontinuation and outcomes in patients with chronic lymphocytic leukemia. JAMA Oncol. 1, 80 (2015).","journal-title":"JAMA Oncol."},{"key":"1927_CR8","doi-asserted-by":"publisher","first-page":"1469","DOI":"10.1182\/blood-2016-06-719294","volume":"129","author":"IE Ahn","year":"2017","unstructured":"Ahn, I. E. et al. Clonal evolution leading to ibrutinib resistance in chronic lymphocytic leukemia. Blood 129, 1469\u20131479 (2017).","journal-title":"Blood"},{"key":"1927_CR9","doi-asserted-by":"publisher","first-page":"2062","DOI":"10.1182\/blood-2014-09-603670","volume":"125","author":"P Jain","year":"2015","unstructured":"Jain, P. et al. Outcomes of patients with chronic lymphocytic leukemia after discontinuing ibrutinib. Blood 125, 2062\u20132067 (2015).","journal-title":"Blood"},{"key":"1927_CR10","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-02329-y","volume":"8","author":"DA Landau","year":"2017","unstructured":"Landau, D. A. et al. The evolutionary landscape of chronic lymphocytic leukemia treated with ibrutinib targeted therapy. Nat. Commun. 8, 2185 (2017).","journal-title":"Nat. Commun."},{"key":"1927_CR11","doi-asserted-by":"publisher","first-page":"957","DOI":"10.1016\/S0002-9440(10)64256-3","volume":"161","author":"S Be\u00e0","year":"2002","unstructured":"Be\u00e0, S. et al. Genetic imbalances in progressed B-cell chronic lymphocytic leukemia and transformed large-cell lymphoma (Richter\u2019s syndrome). Am. J. Pathol. 161, 957\u2013968 (2002).","journal-title":"Am. J. Pathol."},{"key":"1927_CR12","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1002\/hon.932","volume":"28","author":"M Scandurra","year":"2010","unstructured":"Scandurra, M. et al. Genomic profiling of Richter\u2019s syndrome: recurrent lesions and differences with de novo diffuse large B-cell lymphomas. Hematol. Oncol. 28, 62\u201367 (2010).","journal-title":"Hematol. Oncol."},{"key":"1927_CR13","doi-asserted-by":"publisher","first-page":"3391","DOI":"10.1182\/blood-2010-09-302174","volume":"117","author":"D Rossi","year":"2011","unstructured":"Rossi, D. et al. The genetics of Richter syndrome reveals disease heterogeneity and predicts survival after transformation. Blood 117, 3391\u20133401 (2011).","journal-title":"Blood"},{"key":"1927_CR14","doi-asserted-by":"publisher","first-page":"2273","DOI":"10.1084\/jem.20131448","volume":"210","author":"G Fabbri","year":"2013","unstructured":"Fabbri, G. et al. Genetic lesions associated with chronic lymphocytic leukemia transformation to Richter syndrome. J. Exp. Med. 210, 2273\u20132288 (2013).","journal-title":"J. Exp. Med."},{"key":"1927_CR15","doi-asserted-by":"publisher","first-page":"2673","DOI":"10.1182\/blood-2013-03-489518","volume":"122","author":"E Chigrinova","year":"2013","unstructured":"Chigrinova, E. et al. Two main genetic pathways lead to the transformation of chronic lymphocytic leukemia to Richter syndrome. Blood 122, 2673\u20132682 (2013).","journal-title":"Blood"},{"key":"1927_CR16","doi-asserted-by":"publisher","first-page":"2800","DOI":"10.1182\/blood.2020005650","volume":"137","author":"J Klintman","year":"2021","unstructured":"Klintman, J. et al. Genomic and transcriptomic correlates of Richter transformation in chronic lymphocytic leukemia. Blood 137, 2800\u20132816 (2021).","journal-title":"Blood"},{"key":"1927_CR17","doi-asserted-by":"publisher","first-page":"1053","DOI":"10.1182\/blood.2020008276","volume":"138","author":"S Chakraborty","year":"2021","unstructured":"Chakraborty, S. et al. B-cell receptor signaling and genetic lesions in TP53 and CDKN2A\/CDKN2B cooperate in Richter transformation. Blood 138, 1053\u20131066 (2021).","journal-title":"Blood"},{"key":"1927_CR18","doi-asserted-by":"publisher","first-page":"3362","DOI":"10.1182\/blood-2017-01-763003","volume":"129","author":"MA Anderson","year":"2017","unstructured":"Anderson, M. A. et al. Clinicopathological features and outcomes of progression of CLL on the BCL2 inhibitor venetoclax. Blood 129, 3362\u20133370 (2017).","journal-title":"Blood"},{"key":"1927_CR19","doi-asserted-by":"publisher","first-page":"1584","DOI":"10.1182\/bloodadvances.2017007302","volume":"1","author":"CR Miller","year":"2017","unstructured":"Miller, C. R. et al. Near-tetraploidy is associated with Richter transformation in chronic lymphocytic leukemia patients receiving ibrutinib. Blood Adv. 1, 1584\u20131588 (2017).","journal-title":"Blood Adv."},{"key":"1927_CR20","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1182\/bloodadvances.2016003632","volume":"1","author":"S Kadri","year":"2017","unstructured":"Kadri, S. et al. Clonal evolution underlying leukemia progression and Richter transformation in patients with ibrutinib-relapsed CLL. Blood Adv. 1, 715\u2013727 (2017).","journal-title":"Blood Adv."},{"key":"1927_CR21","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-03170-7","volume":"9","author":"CD Herling","year":"2018","unstructured":"Herling, C. D. et al. Clonal dynamics towards the development of venetoclax resistance in chronic lymphocytic leukemia. Nat. Commun. 9, 727 (2018).","journal-title":"Nat. Commun."},{"key":"1927_CR22","doi-asserted-by":"publisher","first-page":"1100","DOI":"10.1038\/leu.2012.357","volume":"27","author":"N Villamor","year":"2013","unstructured":"Villamor, N. et al. NOTCH1 mutations identify a genetic subgroup of chronic lymphocytic leukemia patients with high risk of transformation and poor outcome. Leukemia 27, 1100\u20131106 (2013).","journal-title":"Leukemia"},{"key":"1927_CR23","doi-asserted-by":"publisher","first-page":"1087","DOI":"10.3109\/10428194.2012.723706","volume":"54","author":"L De Paoli","year":"2013","unstructured":"De Paoli, L. et al. MGA, a suppressor of MYC, is recurrently inactivated in high risk chronic lymphocytic leukemia. Leuk. Lymphoma 54, 1087\u20131090 (2013).","journal-title":"Leuk. Lymphoma"},{"key":"1927_CR24","doi-asserted-by":"publisher","first-page":"426","DOI":"10.1111\/j.1365-2141.2012.09155.x","volume":"158","author":"D Rossi","year":"2012","unstructured":"Rossi, D. et al. Different impact of NOTCH1 and SF3B1 mutations on the risk of chronic lymphocytic leukemia transformation to Richter syndrome. Br. J. Haematol. 158, 426\u2013429 (2012).","journal-title":"Br. J. Haematol."},{"key":"1927_CR25","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1080\/10428194.2018.1516878","volume":"60","author":"A Chitalia","year":"2019","unstructured":"Chitalia, A. et al. Descriptive analysis of genetic aberrations and cell of origin in Richter transformation. Leuk. Lymphoma 60, 971\u2013979 (2019).","journal-title":"Leuk. Lymphoma"},{"key":"1927_CR26","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1002\/hon.2915","volume":"39","author":"S Benatti","year":"2021","unstructured":"Benatti, S. et al. IRF4 L116R mutation promotes proliferation of chronic lymphocytic leukemia B cells inducing MYC. Hematol. Oncol. 39, 707\u2013711 (2021).","journal-title":"Hematol. Oncol."},{"key":"1927_CR27","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms15746","volume":"8","author":"C Minici","year":"2017","unstructured":"Minici, C. et al. Distinct homotypic B-cell receptor interactions shape the outcome of chronic lymphocytic leukaemia. Nat. Commun. 8, 15746 (2017).","journal-title":"Nat. Commun."},{"key":"1927_CR28","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1038\/nature14666","volume":"526","author":"XS Puente","year":"2015","unstructured":"Puente, X. S. et al. Non-coding recurrent mutations in chronic lymphocytic leukaemia. Nature 526, 519\u2013524 (2015).","journal-title":"Nature"},{"key":"1927_CR29","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms9866","volume":"6","author":"S Kasar","year":"2015","unstructured":"Kasar, S. et al. Whole-genome sequencing reveals activation-induced cytidine deaminase signatures during indolent chronic lymphocytic leukaemia evolution. Nat. Commun. 6, 8866 (2015).","journal-title":"Nat. Commun."},{"key":"1927_CR30","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11037-8","volume":"10","author":"F Maura","year":"2019","unstructured":"Maura, F. et al. A practical guide for mutational signature analysis in hematological malignancies. Nat. Commun. 10, 2969 (2019).","journal-title":"Nat. Commun."},{"key":"1927_CR31","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06354-3","volume":"9","author":"SE Arthur","year":"2018","unstructured":"Arthur, S. E. et al. Genome-wide discovery of somatic regulatory variants in diffuse large B-cell lymphoma. Nat. Commun. 9, 4001 (2018).","journal-title":"Nat. Commun."},{"key":"1927_CR32","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1038\/s41586-020-1943-3","volume":"578","author":"LB Alexandrov","year":"2020","unstructured":"Alexandrov, L. B. et al. The repertoire of mutational signatures in human cancer. Nature 578, 94\u2013101 (2020).","journal-title":"Nature"},{"key":"1927_CR33","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1016\/j.cell.2019.03.001","volume":"177","author":"JE Kucab","year":"2019","unstructured":"Kucab, J. E. et al. A compendium of mutational signatures of environmental agents. Cell 177, 821\u2013836 (2019).","journal-title":"Cell"},{"key":"1927_CR34","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-15740-9","volume":"11","author":"EH Rustad","year":"2020","unstructured":"Rustad, E. H. et al. Timing the initiation of multiple myeloma. Nat. Commun. 11, 1917 (2020).","journal-title":"Nat. Commun."},{"key":"1927_CR35","doi-asserted-by":"publisher","first-page":"1726","DOI":"10.1016\/j.stem.2021.07.012","volume":"28","author":"JK de Kanter","year":"2021","unstructured":"de Kanter, J. K. et al. Antiviral treatment causes a unique mutational signature in cancers of transplantation recipients. Cell Stem Cell 28, 1726\u20131739 (2021).","journal-title":"Cell Stem Cell"},{"key":"1927_CR36","doi-asserted-by":"publisher","first-page":"1732","DOI":"10.1038\/s41588-019-0525-5","volume":"51","author":"O Pich","year":"2019","unstructured":"Pich, O. et al. The mutational footprints of cancer therapies. Nat. Genet. 51, 1732\u20131740 (2019).","journal-title":"Nat. Genet."},{"key":"1927_CR37","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1038\/s41586-019-1198-z","volume":"569","author":"F Gaiti","year":"2019","unstructured":"Gaiti, F. et al. Epigenetic evolution and lineage histories of chronic lymphocytic leukaemia. Nature 569, 576\u2013580 (2019).","journal-title":"Nature"},{"key":"1927_CR38","doi-asserted-by":"publisher","first-page":"1895","DOI":"10.1182\/blood.2020005216","volume":"137","author":"K Gemenetzi","year":"2021","unstructured":"Gemenetzi, K. et al. Higher-order immunoglobulin repertoire restrictions in CLL: the illustrative case of stereotyped subsets 2 and 169. Blood 137, 1895\u20131904 (2021).","journal-title":"Blood"},{"key":"1927_CR39","doi-asserted-by":"publisher","first-page":"1769","DOI":"10.3389\/fonc.2021.640731","volume":"11","author":"D Bagnara","year":"2021","unstructured":"Bagnara, D. et al. Post-transformation IGHV-IGHD-IGHJ mutations in chronic lymphocytic leukemia B cells: implications for mutational mechanisms and impact on clinical course. Front. Oncol. 11, 1769 (2021).","journal-title":"Front. Oncol."},{"key":"1927_CR40","doi-asserted-by":"publisher","first-page":"4832","DOI":"10.1182\/blood-2009-05-219634","volume":"114","author":"C Calissano","year":"2009","unstructured":"Calissano, C. et al. In vivo intraclonal and interclonal kinetic heterogeneity in B-cell chronic lymphocytic leukemia. Blood 114, 4832\u20134842 (2009).","journal-title":"Blood"},{"key":"1927_CR41","doi-asserted-by":"publisher","first-page":"1374","DOI":"10.2119\/molmed.2011.00360","volume":"17","author":"C Calissano","year":"2011","unstructured":"Calissano, C. et al. Intraclonal complexity in chronic lymphocytic leukemia: fractions enriched in recently born\/divided and older\/quiescent cells. Mol. Med. 17, 1374\u20131382 (2011).","journal-title":"Mol. Med."},{"key":"1927_CR42","doi-asserted-by":"publisher","first-page":"546","DOI":"10.1182\/blood-2014-03-559690","volume":"124","author":"B Cui","year":"2014","unstructured":"Cui, B. et al. MicroRNA-155 influences B-cell receptor signaling and associates with aggressive disease in chronic lymphocytic leukemia. Blood 124, 546\u2013554 (2014).","journal-title":"Blood"},{"key":"1927_CR43","doi-asserted-by":"publisher","first-page":"3048","DOI":"10.1158\/2159-8290.CD-21-0276","volume":"11","author":"L Penter","year":"2021","unstructured":"Penter, L. et al. Longitudinal single-cell dynamics of chromatin accessibility and mitochondrial mutations in chronic lymphocytic leukemia mirror disease history. Cancer Discov. 11, 3048\u20133063 (2021).","journal-title":"Cancer Discov."},{"key":"1927_CR44","doi-asserted-by":"publisher","first-page":"868","DOI":"10.1038\/s41591-018-0028-4","volume":"24","author":"R Beekman","year":"2018","unstructured":"Beekman, R. et al. The reference epigenome and regulatory chromatin landscape of chronic lymphocytic leukemia. Nat. Med. 24, 868\u2013880 (2018).","journal-title":"Nat. Med."},{"key":"1927_CR45","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-22652-9","volume":"12","author":"C-L Chen","year":"2021","unstructured":"Chen, C.-L. et al. Arginine is an epigenetic regulator targeting TEAD4 to modulate OXPHOS in prostate cancer cells. Nat. Commun. 12, 2398 (2021).","journal-title":"Nat. Commun."},{"key":"1927_CR46","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1158\/2159-8290.CD-16-0861","volume":"8","author":"P Rajbhandari","year":"2018","unstructured":"Rajbhandari, P. et al. Cross-cohort analysis identifies a TEAD4\u2013MYCN positive feedback loop as the core regulatory element of high-risk neuroblastoma. Cancer Discov. 8, 582\u2013599 (2018).","journal-title":"Cancer Discov."},{"key":"1927_CR47","doi-asserted-by":"publisher","first-page":"1330","DOI":"10.1038\/s41375-021-01178-5","volume":"35","author":"R Maffei","year":"2021","unstructured":"Maffei, R. et al. IRF4 modulates the response to BCR activation in chronic lymphocytic leukemia regulating IKAROS and SYK. Leukemia 35, 1330\u20131343 (2021).","journal-title":"Leukemia"},{"key":"1927_CR48","doi-asserted-by":"publisher","first-page":"1798","DOI":"10.4049\/jimmunol.2100440","volume":"207","author":"DG Patterson","year":"2021","unstructured":"Patterson, D. G. et al. An IRF4\u2013MYC\u2013mTORC1 integrated pathway controls cell growth and the proliferative capacity of activated B cells during B cell differentiation in vivo. J. Immunol. 207, 1798\u20131811 (2021).","journal-title":"J. Immunol."},{"key":"1927_CR49","doi-asserted-by":"publisher","first-page":"1066","DOI":"10.1038\/s43018-020-00131-2","volume":"1","author":"M Duran-Ferrer","year":"2020","unstructured":"Duran-Ferrer, M. et al. The proliferative history shapes the DNA methylome of B-cell tumors and predicts clinical outcome. Nat. Cancer 1, 1066\u20131081 (2020).","journal-title":"Nat. Cancer"},{"key":"1927_CR50","doi-asserted-by":"publisher","first-page":"1621","DOI":"10.1038\/s41375-020-01055-7","volume":"35","author":"MK Hasan","year":"2021","unstructured":"Hasan, M. K., Ghia, E. M., Rassenti, L. Z., Widhopf, G. F. & Kipps, T. J. Wnt5a enhances proliferation of chronic lymphocytic leukemia and ERK1\/2 phosphorylation via a ROR1\/DOCK2-dependent mechanism. Leukemia 35, 1621\u20131630 (2021).","journal-title":"Leukemia"},{"key":"1927_CR51","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.semcancer.2016.07.001","volume":"39","author":"S Ntoufa","year":"2016","unstructured":"Ntoufa, S., Vilia, M. G., Stamatopoulos, K., Ghia, P. & Muzio, M. Toll-like receptors signaling: a complex network for NF-\u03baB activation in B-cell lymphoid malignancies. Semin. Cancer Biol. 39, 15\u201325 (2016).","journal-title":"Semin. Cancer Biol."},{"key":"1927_CR52","doi-asserted-by":"publisher","first-page":"1851","DOI":"10.1182\/blood-2004-07-2947","volume":"105","author":"S Monti","year":"2005","unstructured":"Monti, S. Molecular profiling of diffuse large B-cell lymphoma identifies robust subtypes including one characterized by host inflammatory response. Blood 105, 1851\u20131861 (2005).","journal-title":"Blood"},{"key":"1927_CR53","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1016\/j.ccr.2012.08.014","volume":"22","author":"P Caro","year":"2012","unstructured":"Caro, P. et al. Metabolic signatures uncover distinct targets in molecular subsets of diffuse large B cell lymphoma. Cancer Cell 22, 547\u2013560 (2012).","journal-title":"Cancer Cell"},{"key":"1927_CR54","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1038\/cdd.2016.116","volume":"24","author":"E Norberg","year":"2017","unstructured":"Norberg, E. et al. Differential contribution of the mitochondrial translation pathway to the survival of diffuse large B-cell lymphoma subsets. Cell Death Differ. 24, 251\u2013262 (2017).","journal-title":"Cell Death Differ."},{"key":"1927_CR55","doi-asserted-by":"publisher","first-page":"1036","DOI":"10.1038\/s41591-018-0052-4","volume":"24","author":"JR Molina","year":"2018","unstructured":"Molina, J. R. et al. An inhibitor of oxidative phosphorylation exploits cancer vulnerability. Nat. Med. 24, 1036\u20131046 (2018).","journal-title":"Nat. Med."},{"key":"1927_CR56","doi-asserted-by":"publisher","first-page":"24980","DOI":"10.18632\/oncotarget.25166","volume":"9","author":"HV Vangapandu","year":"2018","unstructured":"Vangapandu, H. V. et al. Biological and metabolic effects of IACS-010759, an OxPhos inhibitor, on chronic lymphocytic leukemia cells. Oncotarget 9, 24980\u201324991 (2018).","journal-title":"Oncotarget"},{"key":"1927_CR57","doi-asserted-by":"publisher","first-page":"eaau1167","DOI":"10.1126\/scitranslmed.aau1167","volume":"11","author":"L Zhang","year":"2019","unstructured":"Zhang, L. et al. Metabolic reprogramming toward oxidative phosphorylation identifies a therapeutic target for mantle cell lymphoma. Sci. Transl. Med. 11, eaau1167 (2019).","journal-title":"Sci. Transl. Med."},{"key":"1927_CR58","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1038\/nature22353","volume":"546","author":"G Varano","year":"2017","unstructured":"Varano, G. et al. The B-cell receptor controls fitness of MYC-driven lymphoma cells via GSK3\u03b2 inhibition. Nature 546, 302\u2013306 (2017).","journal-title":"Nature"},{"key":"1927_CR59","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1158\/0008-5472.CAN-18-0781","volume":"79","author":"EL Dadashian","year":"2019","unstructured":"Dadashian, E. L. et al. TLR signaling is activated in lymph node\u2013resident CLL cells and is only partially inhibited by ibrutinib. Cancer Res. 79, 360\u2013371 (2019).","journal-title":"Cancer Res."},{"key":"1927_CR60","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1111\/bjh.14062","volume":"177","author":"K-L Chan","year":"2017","unstructured":"Chan, K.-L. et al. Plasmablastic Richter transformation as a resistance mechanism for chronic lymphocytic leukaemia treated with BCR signalling inhibitors. Br. J. Haematol. 177, 324\u2013328 (2017).","journal-title":"Br. J. Haematol."},{"key":"1927_CR61","doi-asserted-by":"publisher","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","volume":"25","author":"H Li","year":"2009","unstructured":"Li, H. & Durbin, R. Fast and accurate short read alignment with Burrows\u2013Wheeler transform. Bioinformatics 25, 1754\u20131760 (2009).","journal-title":"Bioinformatics"},{"key":"1927_CR62","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17095-7","volume":"11","author":"F Nadeu","year":"2020","unstructured":"Nadeu, F. et al. IgCaller for reconstructing immunoglobulin gene rearrangements and oncogenic translocations from whole-genome sequencing in lymphoid neoplasms. Nat. Commun. 11, 3390 (2020).","journal-title":"Nat. Commun."},{"key":"1927_CR63","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1038\/nbt.1754","volume":"29","author":"JT Robinson","year":"2011","unstructured":"Robinson, J. T. et al. Integrative genomics viewer. Nat. Biotechnol. 29, 24\u201326 (2011).","journal-title":"Nat. Biotechnol."},{"key":"1927_CR64","doi-asserted-by":"publisher","first-page":"15.10.1","DOI":"10.1002\/cpbi.20","volume":"56","author":"D Jones","year":"2016","unstructured":"Jones, D. et al. cgpCaVEManWrapper: simple execution of CaVEMan in order to detect somatic single nucleotide variants in NGS data. Curr. Protoc. Bioinforma. 56, 15.10.1\u201315.10.18 (2016).","journal-title":"Curr. Protoc. Bioinforma."},{"key":"1927_CR65","doi-asserted-by":"publisher","first-page":"1297","DOI":"10.1101\/gr.107524.110","volume":"20","author":"A McKenna","year":"2010","unstructured":"McKenna, A. et al. The genome analysis toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 20, 1297\u20131303 (2010).","journal-title":"Genome Res."},{"key":"1927_CR66","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-016-1029-6","volume":"17","author":"Y Fan","year":"2016","unstructured":"Fan, Y. et al. MuSE: accounting for tumor heterogeneity using a sample-specific error model improves sensitivity and specificity in mutation calling from sequencing data. Genome Biol. 17, 178 (2016).","journal-title":"Genome Biol."},{"key":"1927_CR67","doi-asserted-by":"publisher","unstructured":"Danecek, P. et al. Twelve years of SAMtools and BCFtools. Gigascience https:\/\/doi.org\/10.1093\/gigascience\/giab008 (2021).","DOI":"10.1093\/gigascience\/giab008"},{"key":"1927_CR68","doi-asserted-by":"publisher","first-page":"1106","DOI":"10.1038\/nbt.3027","volume":"32","author":"V Moncunill","year":"2014","unstructured":"Moncunill, V. et al. Comprehensive characterization of complex structural variations in cancer by directly comparing genome sequence reads. Nat. Biotechnol. 32, 1106\u20131112 (2014).","journal-title":"Nat. Biotechnol."},{"key":"1927_CR69","doi-asserted-by":"publisher","first-page":"15.7.1","DOI":"10.1002\/0471250953.bi1507s52","volume":"52","author":"KM Raine","year":"2015","unstructured":"Raine, K. M. et al. cgpPindel: identifying somatically acquired insertion and deletion events from paired end sequencing. Curr. Protoc. Bioinforma. 52, 15.7.1\u201312 (2015).","journal-title":"Curr. Protoc. Bioinforma."},{"key":"1927_CR70","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1101\/gr.221028.117","volume":"28","author":"JA Wala","year":"2018","unstructured":"Wala, J. A. et al. SvABA: genome-wide detection of structural variants and indels by local assembly. Genome Res. 28, 581\u2013591 (2018).","journal-title":"Genome Res."},{"key":"1927_CR71","doi-asserted-by":"publisher","first-page":"912","DOI":"10.1038\/ng.3036","volume":"46","author":"A Rimmer","year":"2014","unstructured":"Rimmer, A. et al. Integrating mapping-, assembly- and haplotype-based approaches for calling variants in clinical sequencing applications. Nat. Genet. 46, 912\u2013918 (2014).","journal-title":"Nat. Genet."},{"key":"1927_CR72","doi-asserted-by":"publisher","first-page":"80","DOI":"10.4161\/fly.19695","volume":"6","author":"P Cingolani","year":"2012","unstructured":"Cingolani, P. et al. A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff: SNPs in the genome of Drosophila melanogaster strain w1118; iso-2; iso-3. Fly. (Austin). 6, 80\u201392 (2012).","journal-title":"Fly. (Austin)."},{"key":"1927_CR73","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1038\/leu.2017.291","volume":"32","author":"F Nadeu","year":"2018","unstructured":"Nadeu, F. et al. Clinical impact of the subclonal architecture and mutational complexity in chronic lymphocytic leukemia. Leukemia 32, 645\u2013653 (2018).","journal-title":"Leukemia"},{"key":"1927_CR74","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1101\/gr.129684.111","volume":"22","author":"DC Koboldt","year":"2012","unstructured":"Koboldt, D. C. et al. VarScan 2: somatic mutation and copy number alteration discovery in cancer by exome sequencing. Genome Res. 22, 568\u2013576 (2012).","journal-title":"Genome Res."},{"key":"1927_CR75","doi-asserted-by":"publisher","first-page":"e108","DOI":"10.1093\/nar\/gkw227","volume":"44","author":"Z Lai","year":"2016","unstructured":"Lai, Z. et al. VarDict: a novel and versatile variant caller for next-generation sequencing in cancer research. Nucleic Acids Res. 44, e108 (2016).","journal-title":"Nucleic Acids Res."},{"key":"1927_CR76","doi-asserted-by":"publisher","first-page":"11189","DOI":"10.1093\/nar\/gks918","volume":"40","author":"A Wilm","year":"2012","unstructured":"Wilm, A. et al. LoFreq: a sequence-quality aware, ultra-sensitive variant caller for uncovering cell-population heterogeneity from high-throughput sequencing datasets. Nucleic Acids Res. 40, 11189\u201311201 (2012).","journal-title":"Nucleic Acids Res."},{"key":"1927_CR77","doi-asserted-by":"publisher","first-page":"79485","DOI":"10.18632\/oncotarget.13103","volume":"7","author":"E Muller","year":"2016","unstructured":"Muller, E. et al. OutLyzer: software for extracting low-allele-frequency tumor mutations from sequencing background noise in clinical practice. Oncotarget 7, 79485\u201379493 (2016).","journal-title":"Oncotarget"},{"key":"1927_CR78","doi-asserted-by":"publisher","first-page":"994","DOI":"10.1016\/j.cell.2012.04.023","volume":"149","author":"S Nik-Zainal","year":"2012","unstructured":"Nik-Zainal, S. et al. The life history of 21 breast cancers. Cell 149, 994\u20131007 (2012).","journal-title":"Cell"},{"key":"1927_CR79","doi-asserted-by":"publisher","first-page":"15.9.1","DOI":"10.1002\/cpbi.17","volume":"56","author":"KM Raine","year":"2016","unstructured":"Raine, K. M. et al. ascatNgs: identifying somatically acquired copy-number alterations from whole-genome sequencing data. Curr. Protoc. Bioinforma. 56, 15.9.1\u201315.9.17 (2016).","journal-title":"Curr. Protoc. Bioinforma."},{"key":"1927_CR80","doi-asserted-by":"publisher","first-page":"e1004873","DOI":"10.1371\/journal.pcbi.1004873","volume":"12","author":"E Talevich","year":"2016","unstructured":"Talevich, E., Shain, A. H., Botton, T. & Bastian, B. C. CNVkit: genome-wide copy number detection and visualization from targeted DNA sequencing. PLoS Comput. Biol. 12, e1004873 (2016).","journal-title":"PLoS Comput. Biol."},{"key":"1927_CR81","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1038\/nature17676","volume":"534","author":"S Nik-Zainal","year":"2016","unstructured":"Nik-Zainal, S. et al. Landscape of somatic mutations in 560 breast cancer whole-genome sequences. Nature 534, 47\u201354 (2016).","journal-title":"Nature"},{"key":"1927_CR82","doi-asserted-by":"publisher","first-page":"i333","DOI":"10.1093\/bioinformatics\/bts378","volume":"28","author":"T Rausch","year":"2012","unstructured":"Rausch, T. et al. DELLY: structural variant discovery by integrated paired-end and split-read analysis. Bioinformatics 28, i333\u2013i339 (2012).","journal-title":"Bioinformatics"},{"key":"1927_CR83","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.cell.2010.11.055","volume":"144","author":"PJ Stephens","year":"2011","unstructured":"Stephens, P. J. et al. Massive genomic rearrangement acquired in a single catastrophic event during cancer development. Cell 144, 27\u201340 (2011).","journal-title":"Cell"},{"key":"1927_CR84","doi-asserted-by":"publisher","first-page":"1226","DOI":"10.1016\/j.cell.2013.02.023","volume":"152","author":"JO Korbel","year":"2013","unstructured":"Korbel, J. O. & Campbell, P. J. Criteria for inference of chromothripsis in cancer genomes. Cell 152, 1226\u20131236 (2013).","journal-title":"Cell"},{"key":"1927_CR85","doi-asserted-by":"publisher","first-page":"666","DOI":"10.1016\/j.cell.2013.03.021","volume":"153","author":"SC Baca","year":"2013","unstructured":"Baca, S. C. et al. Punctuated evolution of prostate cancer genomes. Cell 153, 666\u2013677 (2013).","journal-title":"Cell"},{"key":"1927_CR86","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1016\/j.ccr.2013.04.025","volume":"23","author":"MM Shen","year":"2013","unstructured":"Shen, M. M. Chromoplexy: a new category of complex rearrangements in the cancer genome. Cancer Cell 23, 567\u2013569 (2013).","journal-title":"Cancer Cell"},{"key":"1927_CR87","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1038\/s41586-019-1913-9","volume":"578","author":"Y Li","year":"2020","unstructured":"Li, Y. et al. Patterns of somatic structural variation in human cancer genomes. Nature 578, 112\u2013121 (2020).","journal-title":"Nature"},{"key":"1927_CR88","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11680-1","volume":"10","author":"F Maura","year":"2019","unstructured":"Maura, F. et al. Genomic landscape and chronological reconstruction of driver events in multiple myeloma. Nat. Commun. 10, 3835 (2019).","journal-title":"Nat. Commun."},{"key":"1927_CR89","doi-asserted-by":"publisher","first-page":"a026625","DOI":"10.1101\/cshperspect.a026625","volume":"7","author":"SC Dentro","year":"2017","unstructured":"Dentro, S. C., Wedge, D. C. & Van Loo, P. Principles of reconstructing the subclonal architecture of cancers. Cold Spring Harb. Perspect. Med. 7, a026625 (2017).","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"1927_CR90","doi-asserted-by":"publisher","first-page":"600","DOI":"10.1038\/ng.3557","volume":"48","author":"J Kim","year":"2016","unstructured":"Kim, J. et al. Somatic ERCC2 mutations are associated with a distinct genomic signature in urothelial tumors. Nat. Genet. 48, 600\u2013606 (2016).","journal-title":"Nat. Genet."},{"key":"1927_CR91","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1038\/s41586-019-1672-7","volume":"574","author":"H Lee-Six","year":"2019","unstructured":"Lee-Six, H. et al. The landscape of somatic mutation in normal colorectal epithelial cells. Nature 574, 532\u2013537 (2019).","journal-title":"Nature"},{"key":"1927_CR92","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1038\/s43018-021-00230-8","volume":"2","author":"F Yang","year":"2021","unstructured":"Yang, F. et al. Chemotherapy and mismatch repair deficiency cooperate to fuel TP53 mutagenesis and ALL relapse. Nat. Cancer 2, 819\u2013834 (2021).","journal-title":"Nat. Cancer"},{"key":"1927_CR93","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.1016\/j.ajhg.2012.10.018","volume":"91","author":"A Koren","year":"2012","unstructured":"Koren, A. et al. Differential relationship of DNA replication timing to different forms of human mutation and variation. Am. J. Hum. Genet. 91, 1033\u20131040 (2012).","journal-title":"Am. J. Hum. Genet."},{"key":"1927_CR94","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1016\/j.cell.2015.12.050","volume":"164","author":"NJ Haradhvala","year":"2016","unstructured":"Haradhvala, N. J. et al. Mutational strand asymmetries in cancer genomes reveal mechanisms of DNA damage and repair. Cell 164, 538\u2013549 (2016).","journal-title":"Cell"},{"key":"1927_CR95","doi-asserted-by":"publisher","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","volume":"30","author":"AM Bolger","year":"2014","unstructured":"Bolger, A. M., Lohse, M. & Usadel, B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 30, 2114\u20132120 (2014).","journal-title":"Bioinformatics"},{"key":"1927_CR96","doi-asserted-by":"publisher","first-page":"1363","DOI":"10.1093\/bioinformatics\/btu049","volume":"30","author":"MJ Aryee","year":"2014","unstructured":"Aryee, M. J. et al. Minfi: a flexible and comprehensive Bioconductor package for the analysis of Infinium DNA methylation microarrays. Bioinformatics 30, 1363\u20131369 (2014).","journal-title":"Bioinformatics"},{"key":"1927_CR97","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2008-9-9-r137","volume":"9","author":"Y Zhang","year":"2008","unstructured":"Zhang, Y. et al. Model-based analysis of ChIP-Seq (MACS). Genome Biol. 9, R137 (2008).","journal-title":"Genome Biol."},{"key":"1927_CR98","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8","volume":"15","author":"MI Love","year":"2014","unstructured":"Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 550 (2014).","journal-title":"Genome Biol."},{"key":"1927_CR99","doi-asserted-by":"publisher","first-page":"3211","DOI":"10.1093\/bioinformatics\/bts611","volume":"28","author":"E Kopylova","year":"2012","unstructured":"Kopylova, E., No\u00e9, L. & Touzet, H. SortMeRNA: fast and accurate filtering of ribosomal RNAs in metatranscriptomic data. Bioinformatics 28, 3211\u20133217 (2012).","journal-title":"Bioinformatics"},{"key":"1927_CR100","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1038\/nbt.3519","volume":"34","author":"NL Bray","year":"2016","unstructured":"Bray, N. L., Pimentel, H., Melsted, P. & Pachter, L. Near-optimal probabilistic RNA-seq quantification. Nat. Biotechnol. 34, 525\u2013527 (2016).","journal-title":"Nat. Biotechnol."},{"key":"1927_CR101","doi-asserted-by":"publisher","first-page":"1885","DOI":"10.1101\/gr.220707.117","volume":"27","author":"J Kuipers","year":"2017","unstructured":"Kuipers, J., Jahn, K., Raphael, B. J. & Beerenwinkel, N. Single-cell sequencing data reveal widespread recurrence and loss of mutational hits in the life histories of tumors. Genome Res. 27, 1885\u20131894 (2017).","journal-title":"Genome Res."},{"key":"1927_CR102","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19119-8","volume":"11","author":"K Morita","year":"2020","unstructured":"Morita, K. et al. Clonal evolution of acute myeloid leukemia revealed by high-throughput single-cell genomics. Nat. Commun. 11, 5327 (2020).","journal-title":"Nat. Commun."},{"key":"1927_CR103","doi-asserted-by":"publisher","first-page":"1096","DOI":"10.1038\/nmeth.2639","volume":"10","author":"S Picelli","year":"2013","unstructured":"Picelli, S. et al. Smart-seq2 for sensitive full-length transcriptome profiling in single cells. Nat. Methods 10, 1096\u20131098 (2013).","journal-title":"Nat. Methods"},{"key":"1927_CR104","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-018-1603-1","volume":"19","author":"M Stoeckius","year":"2018","unstructured":"Stoeckius, M. et al. Cell Hashing with barcoded antibodies enables multiplexing and doublet detection for single cell genomics. Genome Biol. 19, 224 (2018).","journal-title":"Genome Biol."},{"key":"1927_CR105","doi-asserted-by":"publisher","unstructured":"Parekh, S., Ziegenhain, C., Vieth, B., Enard, W. & Hellmann, I. zUMIs - A fast and flexible pipeline to process RNA sequencing data with UMIs. Gigascience https:\/\/doi.org\/10.1093\/gigascience\/giy059 (2018).","DOI":"10.1093\/gigascience\/giy059"},{"key":"1927_CR106","doi-asserted-by":"publisher","first-page":"3573","DOI":"10.1016\/j.cell.2021.04.048","volume":"184","author":"Y Hao","year":"2021","unstructured":"Hao, Y. et al. Integrated analysis of multimodal single-cell data. Cell 184, 3573\u20133587 (2021).","journal-title":"Cell"},{"key":"1927_CR107","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/j.cels.2018.11.005","volume":"8","author":"SL Wolock","year":"2019","unstructured":"Wolock, S. L., Lopez, R. & Klein, A. M. Scrublet: computational identification of cell doublets in single-cell transcriptomic data. Cell Syst. 8, 281\u2013291 (2019).","journal-title":"Cell Syst."},{"key":"1927_CR108","doi-asserted-by":"publisher","first-page":"1289","DOI":"10.1038\/s41592-019-0619-0","volume":"16","author":"I Korsunsky","year":"2019","unstructured":"Korsunsky, I. et al. Fast, sensitive and accurate integration of single-cell data with Harmony. Nat. Methods 16, 1289\u20131296 (2019).","journal-title":"Nat. Methods"},{"key":"1927_CR109","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1007\/BF02111656","volume":"27","author":"E Gnaiger","year":"1995","unstructured":"Gnaiger, E., Steinlechner-Maran, R., M\u00e9ndez, G., Eberl, T. & Margreiter, R. Control of mitochondrial and cellular respiration by oxygen. J. Bioenerg. Biomembr. 27, 583\u2013596 (1995).","journal-title":"J. Bioenerg. Biomembr."},{"key":"1927_CR110","doi-asserted-by":"publisher","first-page":"901","DOI":"10.4049\/jimmunol.1403189","volume":"195","author":"PKA Mongini","year":"2015","unstructured":"Mongini, P. K. A. et al. TLR-9 and IL-15 synergy promotes the in vitro clonal expansion of chronic lymphocytic leukemia B cells. J. Immunol. 195, 901\u2013923 (2015).","journal-title":"J. Immunol."}],"container-title":["Nature Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41591-022-01927-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41591-022-01927-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41591-022-01927-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,18]],"date-time":"2022-08-18T06:05:25Z","timestamp":1660802725000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41591-022-01927-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8]]},"references-count":110,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2022,8]]}},"alternative-id":["1927"],"URL":"https:\/\/doi.org\/10.1038\/s41591-022-01927-8","relation":{},"ISSN":["1078-8956","1546-170X"],"issn-type":[{"value":"1078-8956","type":"print"},{"value":"1546-170X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8]]},"assertion":[{"value":"10 November 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 July 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 August 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"F.N. has received honoraria from Janssen and AbbVie for speaking at educational activities. J.L.M. is an employee of Omniscope. X.S.P. is cofounder of and holds an equity stake in DREAMgenics. H.H. is cofounder of Omniscope and consultant to MiRXES. E.C. has been a consultant for Takeda, NanoString, AbbVie and Illumina; has received honoraria from Janssen, EUSPharma and Roche for speaking at educational activities; and is an inventor on a Lymphoma and Leukemia Molecular Profiling Project patent \u2018Method for subtyping lymphoma subtypes by means of expression profiling\u2019 (PCT\/US2014\/64161) not related to this project. The remaining authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}