ONCOLINER: A new solution for monitoring, improving, and harmonizing somatic variant calling across genomic oncology centers

Abstract

The characterization of somatic genomic variation associated with the biology of tumors is fundamental for cancer research and personalized medicine, as it guides the reliability and impact of cancer studies and genomic-based decisions in clinical oncology. However, the quality and scope of tumor genome analysis across cancer research centers and hospitals are currently highly heterogeneous, limiting the consistency of tumor diagnoses across hospitals and the possibilities of data sharing and data integration across studies. With the aim of providing users with actionable and personalized recommendations for the overall enhancement and harmonization of somatic variant identification across research and clinical environments, we have developed ONCOLINER. Using specifically designed mosaic and tumorized genomes for the analysis of recall and precision across somatic SNVs, insertions or deletions (indels), and structural variants (SVs), we demonstrate that ONCOLINER is capable of improving and harmonizing genome analysis across three state-of-the-art variant discovery pipelines in genomic oncology.

BSC-CNS discloses support for the research of this work from the European Union’s Horizon 2020 research and innovation programme under EUCANCan (grant agreement no. 825835), the Instituto de Salud Carlos III (ISCIII) and “Unión Europea NextGenerationEU/Mecanismo para la Recuperación y la Resilencia (MRR)/PRTR” under project PMP21/00015, the Departament de Recerca i Universitats de la Generalitat de Catalunya (code: 2021 SGR 01626), and the Science and Innovation Spanish Ministry under project BenchSV (PID2020-119797RB-I00/AEI/10.13039/501100011033). Institut Curie discloses support for the research of this work from the European Union’s Horizon 2020 research and innovation programme under EUCANCan (grant agreement no. 825835) and Cancéropôle Île-de-France (grant GENOPROFILE - RIC2021). The German Cancer Research Center (DKFZ) received funding from the European Union’s Horizon 2020 research and innovation programme and the Canadian Institutes of Health Research under the grant agreement no. 825325. CNAG institutional support was from the Spanish Instituto de Salud Carlos III, Fondo de Investigaciones Sanitarias, and cofunded with ERDF funds (PI19/01772); the Spanish Ministry of Science and Innovation through the Instituto de Salud Carlos III; the 2014–2020 Smart Growth Operating Program and institutional co-financing with the European Regional Development Fund (MINECO/FEDER, BIO2015-71792-P); and the Generalitat de Catalunya through the Departament de Salut, Departament d’Empresa i Coneixement. We acknowledge Hartwig Medical Foundation for their help and contributions to different parts of the study. We specifically thank and highly appreciate the valuable contribution of Matias Mendeville. In addition, we would like to express our sincere gratitude to the Genome in a Bottle Consortium (GIAB), the International Cancer Genome Consortium (ICGC), and The Cancer Genome Atlas (TCGA) for making high-quality data accessible through secure protocols, which have been instrumental to the success of this study.

Peer Reviewed

"Article signat per 18 autors/es: Rodrigo Martín ∙ Nicolás Gaitán ∙ Frédéric Jarlier ∙ Lars Feuerbach ∙ Henri de Soyres ∙ Marc Arbonés ∙ Tom Gutman ∙ Montserrat Puiggròs ∙ Alvaro Ferriz ∙ Asier Gonzalez ∙ Lucía Estelles ∙ Ivo Gut ∙ Salvador Capella-Gutierrez ∙ Lincoln D. Stein ∙ Benedikt Brors ∙ Romina Royo ∙ Philippe Hupé ∙ David Torrents"

Postprint (published version)