PT  - JOURNAL ARTICLE
AU  - Jose Espejo Valle-Inclan
AU  - Nicolle J.M. Besselink
AU  - Ewart de Bruijn
AU  - Daniel L. Cameron
AU  - Jana Ebler
AU  - Joachim Kutzera
AU  - Stef van Lieshout
AU  - Tobias Marschall
AU  - Marcel Nelen
AU  - Andy Wing Chun Pang
AU  - Peter Priestley
AU  - Ivo Renkens
AU  - Margaretha G.M. Roemer
AU  - Markus J. van Roosmalen
AU  - Aaron M. Wenger
AU  - Bauke Ylstra
AU  - Remond J.A. Fijneman
AU  - Wigard P. Kloosterman
AU  - Edwin Cuppen
TI  - A multi-platform reference for somatic structural variation detection
AID  - 10.1101/2020.10.15.340497
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.10.15.340497
4099  - http://biorxiv.org/content/early/2020/10/16/2020.10.15.340497.short
4100  - http://biorxiv.org/content/early/2020/10/16/2020.10.15.340497.full
AB  - Accurate detection of somatic structural variation (SV) in cancer genomes remains a challenging problem. This is in part due to the lack of high-quality gold standard datasets that enable the benchmarking of experimental approaches and bioinformatic analysis pipelines for comprehensive somatic SV detection. Here, we approached this challenge by genome-wide somatic SV analysis of the paired melanoma and normal lymphoblastoid COLO829 cell lines using four different technologies: Illumina HiSeq, Oxford Nanopore, Pacific Biosciences and 10x Genomics. Based on the evidence from multiple technologies combined with extensive experimental validation, including Bionano optical mapping data and targeted detection of candidate breakpoint junctions, we compiled a comprehensive set of true somatic SVs, comprising all SV types. We demonstrate the utility of this resource by determining the SV detection performance of each technology as a function of tumor purity and sequence depth, highlighting the importance of assessing these parameters in cancer genomics projects and data analysis tool evaluation. The reference truth somatic SV dataset as well as the underlying raw multi-platform sequencing data are freely available and are an important resource for community somatic benchmarking efforts.Competing Interest StatementAWCP is an employee of Bionano Genomics. AMW is an employee and shareholder of Pacific Biosciences.