Dataset Information

CNValidator: validating somatic copy-number inference.

ABSTRACT:

Motivation

CNValidator assesses the quality of somatic copy-number calls based on coherency of haplotypes across multiple samples from the same individual. It is applicable to any copy-number calling algorithm, which makes calls independently for each sample. This test is useful in assessing the accuracy of copy-number calls, as well as choosing among alternative copy-number algorithms or tuning parameter values.

Results

On a dataset of somatic samples from individuals with Barrett's Esophagus, CNValidator provided feedback on the correctness of sample ploidy calls and also detected data quality issues.

Availability and implementation

CNValidator is available on GitHub at https://github.com/kuhnerlab/CNValidator.

Supplementary information

Supplementary data are available at Bioinformatics online.

SUBMITTER: Smith LP

PROVIDER: S-EPMC6662281 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

CNValidator: validating somatic copy-number inference.

Smith Lucian P LP Yamato Jon A JA Kuhner Mary K MK

Bioinformatics (Oxford, England) 20190801 15

<h4>Motivation</h4>CNValidator assesses the quality of somatic copy-number calls based on coherency of haplotypes across multiple samples from the same individual. It is applicable to any copy-number calling algorithm, which makes calls independently for each sample. This test is useful in assessing the accuracy of copy-number calls, as well as choosing among alternative copy-number algorithms or tuning parameter values.<h4>Results</h4>On a dataset of somatic samples from individuals with Barret ...[more]

PMID: 30541069

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Project description:Multiple large-scale genomic profiling efforts have been undertaken in osteosarcoma to define the genomic drivers of tumorigenesis, therapeutic response, and disease recurrence. The spatial and temporal intratumor heterogeneity could also play a role in promoting tumor growth and treatment resistance. We conducted longitudinal whole-genome sequencing of 37 tumor samples from 8 patients with relapsed or refractory osteosarcoma. Each patient had at least one sample from a primary site and a metastatic or relapse site. Subclonal copy-number alterations were identified in all patients except one. In 5 patients, subclones from the primary tumor emerged and dominated at subsequent relapses. MYC gain/amplification was enriched in the treatment-resistant clones in 6 of 7 patients with multiple clones. Amplifications in other potential driver genes, such as CCNE1, RAD21, VEGFA, and IGF1R, were also observed in the resistant copy-number clones. A chromosomal duplication timing analysis revealed that complex genomic rearrangements typically occurred prior to diagnosis, supporting a macroevolutionary model of evolution, where a large number of genomic aberrations are acquired over a short period of time followed by clonal selection, as opposed to ongoing evolution. A mutational signature analysis of recurrent tumors revealed that homologous repair deficiency (HRD)-related SBS3 increases at each time point in patients with recurrent disease, suggesting that HRD continues to be an active mutagenic process after diagnosis. Overall, by examining the clonal relationships between temporally and spatially separated samples from patients with relapsed/refractory osteosarcoma, this study sheds light on the intratumor heterogeneity and potential drivers of treatment resistance in this disease.SignificanceThe chemoresistant population in recurrent osteosarcoma is subclonal at diagnosis, emerges at the time of primary resection due to selective pressure from neoadjuvant chemotherapy, and is characterized by unique oncogenic amplifications.

Dataset Information

CNValidator: validating somatic copy-number inference.

Motivation

Results

Availability and implementation

Supplementary information

Publications

CNValidator: validating somatic copy-number inference.

Similar Datasets

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