PT  - JOURNAL ARTICLE
AU  - Xinping Fan
AU  - Guanghao Luo
AU  - Yu S. Huang
TI  - Accucopy: Accurate and Fast Inference of Allele-specific Copy Number Alterations from Low-coverage Low-purity Tumor Sequencing Data
AID  - 10.1101/2020.01.02.892364
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.01.02.892364
4099  - http://biorxiv.org/content/early/2020/07/30/2020.01.02.892364.short
4100  - http://biorxiv.org/content/early/2020/07/30/2020.01.02.892364.full
AB  - Background Copy number alterations (CNAs), due to its large impact on the genome, have been an important contributing factor to oncogenesis and metastasis. Detecting genomic alterations from the shallow-sequencing data of a low-purity tumor sample remains a challenging task.Results We introduce Accucopy, a CNA-calling method that improves and adds another layer to our previous Accurity model to predict both total (TCN) and allele-specific copy numbers (ASCN) for the tumor genome. Accucopy adopts a tiered Gaussian mixture model coupled with an innovative autocorrelation-guided EM algorithm to find the optimal solution quickly. The Accucopy model utilizes information from both total sequencing coverage and allelic sequencing coverage. Accucopy is implemented in C++/Rust, available at http://www.yfish.org/software/.Conclusions We describe Accucopy, a method that can predict both TCNs and ASCNs from low-coverage low-purity tumor sequencing data. Through comparative analyses in both simulated and real-sequencing samples, we demonstrate that Accucopy is more accurate than existing methods.Competing Interest StatementThe authors have declared no competing interest.CNAsCopy number alterationsTCNtotal copy numberASCNallele-specific copy numbersSCNAssomatic copy number alterationsHGSNVsheterozygous single-nucleotide lociSKYspectral karyotypingLOHLoss-of-HeterozygosityBRCAbreast invasive carcinomaCOADColon adenocarcinomaGBMGlioblastoma multiformeHNSCHead and Neck squamous cell carcinomaPRADProstate adenocarcinomaCBScircular binary segmentationMACNMajor Allele Copy NumberTRETumor Read EnrichmentLARLog ratio of Allelic-coverage RatiosCNVscopy number variations