HATCHet2: Clone- and haplotype-specific copy number inference from bulk tumor sequencing data Journal Article
| Authors: | Myers, M. A.; Arnold, B. J.; Bansal, V.; Balaban, M.; Mullen, K. M.; Zaccaria, S.; Raphael, B. J. |
| Article Title: | HATCHet2: Clone- and haplotype-specific copy number inference from bulk tumor sequencing data |
| Abstract: | Bulk DNA sequencing of multiple samples from the same tumor is becoming common, yet most methods to infer copy-number aberrations (CNAs) from this data analyze individual samples independently. We introduce HATCHet2, an algorithm to identify haplotype- and clone-specific CNAs simultaneously from multiple bulk samples. HATCHet2 extends the earlier HATCHet method by improving identification of focal CNAs and introducing a novel statistic, the minor haplotype B-allele frequency (mhBAF), that enables identification of mirrored-subclonal CNAs. We demonstrate HATCHet2’s improved accuracy using simulations and a single-cell sequencing dataset. HATCHet2 analysis of 10 prostate cancer patients reveals previously unreported mirrored-subclonal CNAs affecting cancer genes. © The Author(s) 2024. |
| Keywords: | adult; clinical article; controlled study; human cell; single nucleotide polymorphism; somatic mutation; gene deletion; genetics; comparative study; neoplasm; neoplasms; cell proliferation; accuracy; allele; gene; gene amplification; cohort analysis; gene locus; gene frequency; haplotypes; algorithms; protein p53; haplotype; prostate cancer; simulation; prostatic neoplasms; algorithm; prostate tumor; gene fusion; genomics; gaussian mixture model; bioinformatics; conceptual framework; dna extraction; chromosome 13; chromosome 1q; calculation; sequence analysis, dna; dna copy number variations; clone; genetic parameters; copy number variation; single cell analysis; single-cell analysis; chromosome 10; chromosome arm; tumor heterogeneity; hidden markov model; germline mutation; procedures; maximum likelihood method; machine learning; the cancer genome atlas; genomic region; klk2 gene; factorization; dna sequencing; cancer; humans; human; male; article; hierarchical clustering; spop gene; slc45a3 gene; allele-specific; genetic distance; clustering algorithm; homologous chromosome; copy-number aberrations; allelic imbalance signal; b allele frequency; cant1 gene; copy number inference; elk4 gene; fractional copy number; haplotype b allele frequency; haplotype frequency; hatchet2 algorithm; hnrnpa2b1 gene; iliac lymph node metastasis; minor haplotype b allele frequency; parental haplotype; piecewise segmentation; read depth ratio; segment length; sequencing coverage; single cell whole genome sequencing; variable width binning |
| Journal Title: | Genome Biology |
| Volume: | 25 |
| ISSN: | 1465-6906 |
| Publisher: | Biomed Central Ltd |
| Date Published: | 2024-05-21 |
| Start Page: | 130 |
| Language: | English |
| DOI: | 10.1186/s13059-024-03267-x |
| PUBMED: | 38773520 |
| PROVIDER: | scopus |
| PMCID: | PMC11110434 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
