{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T04:14:49Z","timestamp":1784780089071,"version":"3.55.0"},"update-to":[{"DOI":"10.1371\/journal.pgen.1010300","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,10,27]],"date-time":"2022-10-27T00:00:00Z","timestamp":1666828800000}}],"reference-count":86,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T00:00:00Z","timestamp":1665964800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100017473","name":"Australian Genomics Health Alliance","doi-asserted-by":"publisher","award":["1113531"],"award-info":[{"award-number":["1113531"]}],"id":[{"id":"10.13039\/501100017473","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Beat Cancer"},{"name":"Leukemia Foundation"},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1160833"],"award-info":[{"award-number":["1160833"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1146253"],"award-info":[{"award-number":["1146253"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018675","name":"Kids' Cancer Project","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100018675","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Peter Nelson Leukaemia Research Fellow"},{"name":"Australian Research Training Program"},{"name":"Australian Research Training Program"}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>RNA-sequencing (RNA-seq) efforts in acute lymphoblastic leukaemia (ALL) have identified numerous prognostically significant genomic alterations which can guide diagnostic risk stratification and treatment choices when detected early. However, integrating RNA-seq in a clinical setting requires rapid detection and accurate reporting of clinically relevant alterations. Here we present RaScALL, an implementation of the k-mer based variant detection tool<jats:italic>km<\/jats:italic>, capable of identifying more than 100 prognostically significant lesions observed in ALL, including gene fusions, single nucleotide variants and focal gene deletions. We compared genomic alterations detected by RaScALL and those reported by alignment-based<jats:italic>de novo<\/jats:italic>variant detection tools in a study cohort of 180 Australian patient samples. Results were validated using 100 patient samples from a published North American cohort. RaScALL demonstrated a high degree of accuracy for reporting subtype defining genomic alterations. Gene fusions, including difficult to detect fusions involving<jats:italic>EPOR<\/jats:italic>and<jats:italic>DUX4<\/jats:italic>, were accurately identified in 98% of reported cases in the study cohort (n = 164) and 95% of samples (n = 63) in the validation cohort. Pathogenic sequence variants were correctly identified in 75% of tested samples, including all cases involving subtype defining variants<jats:italic>PAX5<\/jats:italic>p.P80R (n = 12) and<jats:italic>IKZF1<\/jats:italic>p.N159Y (n = 4). Intragenic<jats:italic>IKZF1<\/jats:italic>deletions resulting in aberrant transcript isoforms were also detectable with 98% accuracy. Importantly, the median analysis time for detection of all targeted alterations averaged 22 minutes per sample, significantly shorter than standard alignment-based approaches. The application of RaScALL enables rapid identification and reporting of previously identified genomic alterations of known clinical relevance.<\/jats:p>","DOI":"10.1371\/journal.pgen.1010300","type":"journal-article","created":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T17:37:45Z","timestamp":1666028265000},"page":"e1010300","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":24,"title":["RaScALL: Rapid (Ra) screening (Sc) of RNA-seq data for prognostically significant genomic alterations in acute lymphoblastic leukaemia 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