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

Alexandre Eeckhoutte; Alexandre Houy; Elodie Manié; Manon Reverdy; Ivan Bièche; Elisabetta Marangoni; Oumou Goundiam; Anne Vincent-Salomon; Dominique Stoppa-Lyonnet; François-Clément Bidard; Marc-Henri Stern; Tatiana Popova

doi:10.1093/bioinformatics/btaa261

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

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

Authors

Alexandre Eeckhoutte^{1

2}, Alexandre Houy^{1

2}, Elodie Manié^{1

2}, Manon Reverdy^{1

2}, Ivan Bièche³, Elisabetta Marangoni^{2

4}, Oumou Goundiam^{2

4}, Anne Vincent-Salomon⁵, Dominique Stoppa-Lyonnet^{1

6}, François-Clément Bidard^{7

8}, Marc-Henri Stern^{1

2

3}, Tatiana Popova^{1

2}

Affiliations

¹ DNA Repair and Uveal Melanoma (D.R.U.M.), Inserm U830, Institut Curie, Paris 75248, France.
² Institut Curie, PSL Research University, Paris 75005, France.
³ Department of Genetics, Institut Curie, Paris 75248, France.
⁴ Department of Translational Research, Institut Curie PSL Research University, Paris 75248, France.
⁵ Department of Biopathology, Institut Curie PSL Research University, Paris 75005, France.
⁶ Faculty of Medicine, University of Paris, Paris, France.
⁷ Department of Medical Oncology, Institut Curie PSL Research University, Paris 75248, France.
⁸ Versailles Saint Quentin en Yvelines University, Paris Saclay University, Versailles 78035, France.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

DNA Copy Number Variations*
Homologous Recombination
Humans
Neoplasms* / genetics
Software
Whole Genome Sequencing