DOI: 10.6084/m9.figshare.12301898.v1
title: Metadata and supplementary data supporting the published article: Using Whole Genome Sequencing data to derive the homologous recombination deficiency scores.

description: The Homologous Recombination Deficiency (HRD) score was developed using whole genome copy number data derived from arrays as a way to infer deficiency in the homologous recombination DNA damage repair pathway (in particular <i>BRCA1</i> or <i>BRCA2</i> deficiency) in breast cancer samples. In this study, the authors compared HRD scores calculated from DNA copy number data obtained from arrays, whole genome sequencing (WGS) and in downsampled, low coverage WGS data from a cohort of familial breast cancers.<br><b>Data access</b>: All the data supporting the findings of this study are publicly available in the figshare repository. Segmentation data from ASCAT (array data) are available from <b>https://doi.org/10.6084/m9.figshare.9808496</b> and ascatNGS (for original(<b>https://doi.org/10.6084/m9.figshare.9808505</b>) and downsampled WGS data (30X:<b>https://doi.org/10.6084/m9.figshare.9808511</b>, 15X:<b>https://doi.org/10.6084/m9.figshare.9808514</b>, 10X:<b>https://doi.org/10.6084/m9.figshare.9808517</b>)). Supplementary Figure 1 was generated using these data. The HRD score and HRD score components matrixobtained for the array data, are available from the following record: <b>https://doi.org/10.6084/m9.figshare.9808526</b>. Similar data for the original coverageWGS data are located here: <b>https://doi.org/10.6084/m9.figshare.9808529</b> and theHRD score matrices for the downsampled WGS data are found here: <b>https://doi.org/10.6084/m9.figshare.9809978</b> (30X), here: <b>https://doi.org/10.6084/m9.figshare.9810053</b> (15X) and here: <b>https://doi.org/10.6084/m9.figshare.9820646</b> (10X). Figures 1, 2 and 3 were derived from these data. The WGS performance and GC bias metrics for the four differentially classified samples between original coverage and downsampled WGS derived HRD score are available here: <b>https://doi.org/10.6084/m9.figshare.9810164</b> (WGS performance metrics) and here:<b>https://doi.org/10.6084/m9.figshare.9810212</b> (GC bias metrics). Supplementary Figure 3 is derived from these data. The WGS performance and GC bias metrics for the three samples that failed to run using downsampled WGS data are available here:<b>https://doi.org/10.6084/m9.figshare.9810218</b> (WGS performance metrics) and here:<b>https://doi.org/10.6084/m9.figshare.9810221</b> (GC bias metrics). Supplementary Figure 6 is derived from these data. Data for the Circos plots of tumours FBC050798, FBC020636, FBC060411, FBC070086, FBC013587, FBC040197 and FBC030130, are also available on figshare in the following data records: <b>https://doi.org/10.6084/m9.figshare.12271529 </b>(FBC013587), <b>https://doi.org/10.6084/m9.figshare.12271868</b> (FBC040197), <b>https://doi.org/10.6084/m9.figshare.12271961 </b>(FBC050798), <b>https://doi.org/10.6084/m9.figshare.12271859</b> (FBC070086), <b>https://doi.org/10.6084/m9.figshare.12271538 </b>(FBC060411), <b>https://doi.org/10.6084/m9.figshare.12271871</b> (FBC020636) and <b>https://doi.org/10.6084/m9.figshare.12271877</b> (FBC030130). Supplementary tables 1-5 are available in figshare as part of this data record (<b>https://doi.org/10.6084/m9.figshare.12301898)</b>. The whole genome sequencing data analysed during this study are available in the European Genome-phenome Archive here: <b>https://identifiers.org/ega.study:EGAS00001003305</b>. <br><b>Patient consent and study approval</b>: Each tissue bank providing samples had received written informed consent from all the patients involved. Work performed was covered by Human Research Ethics Committee approval from the University of Queensland (2005000785) and QIMR Berghofer Human Research Ethics Committee (P3527).<br><b>Study aims and methodology:</b> The identification of tumours that are deficient in the homologous recombination (HR) DNA damage repair pathway is clinically important, as these tumours have been shown to be sensitive to DNA-damaging therapy, such as platinating chemotherapeutic agents, and poly-(ADP-ribose) polymerase-inhibitors (PARP-i). Here, the authors compared HRD scores calculated from DNA copy number data obtained from arrays, WGS and in downsampled, low coverage WGS data from a cohort of familial breast cancers.In the current study, the authors analysed a series of 67 patients that had both array and WGS data for normal and tumour samples. The patients harboured known pathogenic germline mutations in <i>BRCA1</i> or <i>BRCA2</i> or were from individuals in high risk, breast cancer families who were negative for <i>BRCA1</i> or <i>BRCA2</i> mutations (non-<i>BRCA1/2</i>) following germline testing.The following techniques are described in more detail in the published article: Derivation of B-allele frequencies, logR ratios, HRD score and HRD score components from array- and WGS-derived data, Downsampling of WGS data, Derivation of dLRS, MAPD, Derivation of deviation in segmented Log2 ratio and correlation in Log2 ratio data, Measurement of agreement between array-, original-WGS- and downsampled- WGS-derived HRD score and HRD score components, and Statistical analyses.<br><b>Data supporting the figures and supplementary files in the published article:</b> Data file <b>de Luca et al.xlsx</b> contains all the datasets supporting the figures and supplementary files in the published article. Additionally, the file contains the file formats of individual datasets and the persistent link to each dataset. Supplementary tables <b>Supplementary Table S1.xlsx</b>, <b>Supplementary Table S2.xlsx</b>, <b>Supplementary Table S3.xlsx</b>, <b>Supplementary Table S4.xlsx</b> and <b>Supplementary Table S5.xlsx</b> are part of this figshare data record.The descriptions of these datasets are as follows:Supplementary Table S1.xlsx: Table summarizing the results for comparison of the array- and WGS-derived HRD score.Supplementary Table S2.xlsx: This table contains information about the cellularity, sequencing coverage, HRD score as well as genomic indices of instability for the cohort of 67 patients used in this study.Supplementary Table S3.xlsx: Contingency table for the HR status classification derived from array and WGSSupplementary Table S4.xlsx: Data comparing the HRD score data derived from original WGS (~70X) and downsampled WGS (30x,15x and 10X)Supplementary Table S5.xlsx: Contingency table for the HR status derived from original- (~70X) and downsampled- (30X, 15X and 10X) WGS data<br>