Research output: Contribution to journal › Article › peer-review
BRACNAC: A BRCA1 and BRCA2 Copy Number Alteration Caller from Next-Generation Sequencing Data. / Kechin, Andrey; Boyarskikh, Ulyana; Borobova, Viktoriya et al.
In: International Journal of Molecular Sciences, Vol. 24, No. 23, 16630, 22.11.2023.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - BRACNAC: A BRCA1 and BRCA2 Copy Number Alteration Caller from Next-Generation Sequencing Data
AU - Kechin, Andrey
AU - Boyarskikh, Ulyana
AU - Borobova, Viktoriya
AU - Khrapov, Evgeniy
AU - Subbotin, Sergey
AU - Filipenko, Maxim
N1 - The study was supported by the Russian State funded budget project of ICBFM SB RAS # 121031300045-2 “Fundamentals of Health Preservation”.
PY - 2023/11/22
Y1 - 2023/11/22
N2 - Detecting copy number variations (CNVs) and alterations (CNAs) in the BRCA1 and BRCA2 genes is essential for testing patients for targeted therapy applicability. However, the available bioinformatics tools were initially designed for identifying CNVs/CNAs in whole-genome or -exome (WES) NGS data or targeted NGS data without adaptation to the BRCA1/2 genes. Most of these tools were tested on sample cohorts of limited size, with their use restricted to specific library preparation kits or sequencing platforms. We developed BRACNAC, a new tool for detecting CNVs and CNAs in the BRCA1 and BRCA2 genes in NGS data of different origin. The underlying mechanism of this tool involves various coverage normalization steps complemented by CNV probability evaluation. We estimated the sensitivity and specificity of our tool to be 100% and 94%, respectively, with an area under the curve (AUC) of 94%. The estimation was performed using the NGS data obtained from 213 ovarian and prostate cancer samples tested with in-house and commercially available library preparation kits and additionally using multiplex ligation-dependent probe amplification (MLPA) (12 CNV-positive samples). Using freely available WES and targeted NGS data from other research groups, we demonstrated that BRACNAC could also be used for these two types of data, with an AUC of up to 99.9%. In addition, we determined the limitations of the tool in terms of the minimum number of samples per NGS run (≥20 samples) and the minimum expected percentage of CNV-negative samples (≥80%). We expect that our findings will improve the efficacy of BRCA1/2 diagnostics. BRACNAC is freely available at the GitHub server.
AB - Detecting copy number variations (CNVs) and alterations (CNAs) in the BRCA1 and BRCA2 genes is essential for testing patients for targeted therapy applicability. However, the available bioinformatics tools were initially designed for identifying CNVs/CNAs in whole-genome or -exome (WES) NGS data or targeted NGS data without adaptation to the BRCA1/2 genes. Most of these tools were tested on sample cohorts of limited size, with their use restricted to specific library preparation kits or sequencing platforms. We developed BRACNAC, a new tool for detecting CNVs and CNAs in the BRCA1 and BRCA2 genes in NGS data of different origin. The underlying mechanism of this tool involves various coverage normalization steps complemented by CNV probability evaluation. We estimated the sensitivity and specificity of our tool to be 100% and 94%, respectively, with an area under the curve (AUC) of 94%. The estimation was performed using the NGS data obtained from 213 ovarian and prostate cancer samples tested with in-house and commercially available library preparation kits and additionally using multiplex ligation-dependent probe amplification (MLPA) (12 CNV-positive samples). Using freely available WES and targeted NGS data from other research groups, we demonstrated that BRACNAC could also be used for these two types of data, with an AUC of up to 99.9%. In addition, we determined the limitations of the tool in terms of the minimum number of samples per NGS run (≥20 samples) and the minimum expected percentage of CNV-negative samples (≥80%). We expect that our findings will improve the efficacy of BRCA1/2 diagnostics. BRACNAC is freely available at the GitHub server.
UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85179357158&origin=inward&txGid=ea2b1ff15a55c355fb0126834b72d093
U2 - 10.3390/ijms242316630
DO - 10.3390/ijms242316630
M3 - Article
C2 - 38068953
VL - 24
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 23
M1 - 16630
ER -
ID: 59330025