GSA: an independent development algorithm for calling copy number and detecting homologous recombination deficiency (HRD) from target capture sequencing

Abstract Background The gain or loss of large chromosomal regions or even whole chromosomes is termed as genomic scarring and can be observed as copy number variations resulting from the failure of DNA damage repair. Results In this study, a new algorithm called genomic scar analysis (GSA) has devel...

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Autores principales:	Dongju Chen, Minghui Shao, Pei Meng, Chunli Wang, Qi Li, Yuhang Cai, Chengcheng Song, Xi Wang, Taiping Shi
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Copy number variations Segmentation Tumor purity and ploidy correction Genomic scar analysis Homologous recombination deficiency Computer applications to medicine. Medical informatics R858-859.7 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/60743a88821147f489c4a6aab493a66a
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spelling	oai:doaj.org-article:60743a88821147f489c4a6aab493a66a2021-11-28T12:11:15ZGSA: an independent development algorithm for calling copy number and detecting homologous recombination deficiency (HRD) from target capture sequencing10.1186/s12859-021-04487-91471-2105https://doaj.org/article/60743a88821147f489c4a6aab493a66a2021-11-01T00:00:00Zhttps://doi.org/10.1186/s12859-021-04487-9https://doaj.org/toc/1471-2105Abstract Background The gain or loss of large chromosomal regions or even whole chromosomes is termed as genomic scarring and can be observed as copy number variations resulting from the failure of DNA damage repair. Results In this study, a new algorithm called genomic scar analysis (GSA) has developed and validated to calculate homologous recombination deficiency (HRD) score. The two critical submodules were tree recursion (TR) segmentation and filtering, and the estimation and correction of the tumor purity and ploidy. Then, this study evaluated the rationality of segmentation and genotype identification by the GSA algorithm and compared with other two algorithms, PureCN and ASCAT, found that the segmentation result of GSA algorithm was more logical. In addition, the results indicated that the GSA algorithm had an excellent predictive effect on tumor purity and ploidy, if the tumor purity was more than 20%. Furtherly, this study evaluated the HRD scores and BRCA1/2 deficiency status of 195 clinical samples, and the results indicated that the accuracy was 0.98 (comparing with Affymetrix OncoScan™ assay) and the sensitivity was 95.2% (comparing with BRCA1/2 deficiency status), both were well-behaved. Finally, HRD scores and 16 genes mutations (TP53 and 15 HRR pathway genes) were analyzed in 17 cell lines, the results showed that there was higher frequency in HRR pathway genes in high HRD score samples. Conclusions This new algorithm, named as GSA, could effectively and accurately calculate the purity and ploidy of tumor samples through NGS data, and then reflect the degree of genomic instability and large-scale copy number variations of tumor samples.Dongju ChenMinghui ShaoPei MengChunli WangQi LiYuhang CaiChengcheng SongXi WangTaiping ShiBMCarticleCopy number variationsSegmentationTumor purity and ploidy correctionGenomic scar analysisHomologous recombination deficiencyComputer applications to medicine. Medical informaticsR858-859.7Biology (General)QH301-705.5ENBMC Bioinformatics, Vol 22, Iss 1, Pp 1-19 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Copy number variations Segmentation Tumor purity and ploidy correction Genomic scar analysis Homologous recombination deficiency Computer applications to medicine. Medical informatics R858-859.7 Biology (General) QH301-705.5
spellingShingle	Copy number variations Segmentation Tumor purity and ploidy correction Genomic scar analysis Homologous recombination deficiency Computer applications to medicine. Medical informatics R858-859.7 Biology (General) QH301-705.5 Dongju Chen Minghui Shao Pei Meng Chunli Wang Qi Li Yuhang Cai Chengcheng Song Xi Wang Taiping Shi GSA: an independent development algorithm for calling copy number and detecting homologous recombination deficiency (HRD) from target capture sequencing
description	Abstract Background The gain or loss of large chromosomal regions or even whole chromosomes is termed as genomic scarring and can be observed as copy number variations resulting from the failure of DNA damage repair. Results In this study, a new algorithm called genomic scar analysis (GSA) has developed and validated to calculate homologous recombination deficiency (HRD) score. The two critical submodules were tree recursion (TR) segmentation and filtering, and the estimation and correction of the tumor purity and ploidy. Then, this study evaluated the rationality of segmentation and genotype identification by the GSA algorithm and compared with other two algorithms, PureCN and ASCAT, found that the segmentation result of GSA algorithm was more logical. In addition, the results indicated that the GSA algorithm had an excellent predictive effect on tumor purity and ploidy, if the tumor purity was more than 20%. Furtherly, this study evaluated the HRD scores and BRCA1/2 deficiency status of 195 clinical samples, and the results indicated that the accuracy was 0.98 (comparing with Affymetrix OncoScan™ assay) and the sensitivity was 95.2% (comparing with BRCA1/2 deficiency status), both were well-behaved. Finally, HRD scores and 16 genes mutations (TP53 and 15 HRR pathway genes) were analyzed in 17 cell lines, the results showed that there was higher frequency in HRR pathway genes in high HRD score samples. Conclusions This new algorithm, named as GSA, could effectively and accurately calculate the purity and ploidy of tumor samples through NGS data, and then reflect the degree of genomic instability and large-scale copy number variations of tumor samples.
format	article
author	Dongju Chen Minghui Shao Pei Meng Chunli Wang Qi Li Yuhang Cai Chengcheng Song Xi Wang Taiping Shi
author_facet	Dongju Chen Minghui Shao Pei Meng Chunli Wang Qi Li Yuhang Cai Chengcheng Song Xi Wang Taiping Shi
author_sort	Dongju Chen
title	GSA: an independent development algorithm for calling copy number and detecting homologous recombination deficiency (HRD) from target capture sequencing
title_short	GSA: an independent development algorithm for calling copy number and detecting homologous recombination deficiency (HRD) from target capture sequencing
title_full	GSA: an independent development algorithm for calling copy number and detecting homologous recombination deficiency (HRD) from target capture sequencing
title_fullStr	GSA: an independent development algorithm for calling copy number and detecting homologous recombination deficiency (HRD) from target capture sequencing
title_full_unstemmed	GSA: an independent development algorithm for calling copy number and detecting homologous recombination deficiency (HRD) from target capture sequencing
title_sort	gsa: an independent development algorithm for calling copy number and detecting homologous recombination deficiency (hrd) from target capture sequencing
publisher	BMC
publishDate	2021
url	https://doaj.org/article/60743a88821147f489c4a6aab493a66a
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GSA: an independent development algorithm for calling copy number and detecting homologous recombination deficiency (HRD) from target capture sequencing

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