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. 2020 Jun 1;36(12):3888-3889.
doi: 10.1093/bioinformatics/btaa261.

ShallowHRD: detection of homologous recombination deficiency from shallow whole genome sequencing

Alexandre Eeckhoutte  1   2 , Alexandre Houy  1   2 , Elodie Manié  1   2 , Manon Reverdy  1   2 , Ivan Bièche  3 , Elisabetta Marangoni  2   4 , Oumou Goundiam  2   4 , Anne Vincent-Salomon  5 , Dominique Stoppa-Lyonnet  1   6 , François-Clément Bidard  7   8 , Marc-Henri Stern  1   2   3 , Tatiana Popova  1   2
Affiliations

ShallowHRD: detection of homologous recombination deficiency from shallow whole genome sequencing

Alexandre Eeckhoutte et al. Bioinformatics. .

Abstract

Summary: We introduce shallowHRD, a software tool to evaluate tumor homologous recombination deficiency (HRD) based on whole genome sequencing (WGS) at low coverage (shallow WGS or sWGS; ∼1X coverage). The tool, based on mining copy number alterations profile, implements a fast and straightforward procedure that shows 87.5% sensitivity and 90.5% specificity for HRD detection. shallowHRD could be instrumental in predicting response to poly(ADP-ribose) polymerase inhibitors, to which HRD tumors are selectively sensitive. shallowHRD displays efficiency comparable to most state-of-art approaches, is cost-effective, generates low-storable outputs and is also suitable for fixed-formalin paraffin embedded tissues.

Availability and implementation: shallowHRD R script and documentation are available at https://github.com/aeeckhou/shallowHRD.

Supplementary information: Supplementary data are available at Bioinformatics online.

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Figures

Fig. 1.
Fig. 1.
shallowHRD validation in down-sampled WGS of the TCGA (A) and performance (B). Proven/No HRD: cases with/without inactivation of BRCA1/2, RAD51C or PALB2 (Supplementary Material); HRD (red) and non-HRD (blue) cases in SNP-arrays; LGAs: large-scale genomic alterations; WES: whole exome sequencing. aLow specificity could be due to non-complete annotation of HRD
See this image and copyright information in PMC

References

    1. Abkevich V. et al. (2012) Patterns of genomic loss of heterozygosity predict homologous recombination repair defects in epithelial ovarian cancer. Br. J. Cancer, 107, 1776–1782. - PMC - PubMed
    1. Birkbak N.J. et al. (2012) Telomeric allelic imbalance indicates defective DNA repair and sensitivity to DNA-damaging agents. Cancer Discov., 2, 366–375. - PMC - PubMed
    1. Boeva V. et al. (2012) Control-FREEC: a tool for assessing copy number and allelic content using next-generation sequencing data. Bioinformatics, 28, 423–425. - PMC - PubMed
    1. Coleman R.L. et al. (2019) Veliparib with first-line chemotherapy and as maintenance therapy in ovarian cancer. N. Engl. J. Med., 381, 2403–2415. - PMC - PubMed
    1. Davies H. et al. (2017) HRDetect is a predictor of BRCA1 and BRCA2 deficiency based on mutational signatures. Nat. Med., 23, 517–525. - PMC - PubMed

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