Intersect-then-combine approach: improving the performance of somatic variant calling in whole exome sequencing data using multiple aligners and callers
Authors
Callari, Maurizio
De, Mattos-Arruda Leticia
Rueda, Oscar M
Publication Date
2017-04-18Journal Title
Genome Medicine
ISSN
1756-994X
Volume
9
Number
35
Type
Article
Metadata
Show full item recordCitation
Callari, M., Sammut, S., De, M. L., Bruna, A., Rueda, O. M., Chin, S., & Caldas, C. (2017). Intersect-then-combine approach: improving the performance of somatic variant calling in whole exome sequencing data using multiple aligners and callers. Genome Medicine, 9 (35)https://doi.org/10.1186/s13073-017-0425-1
Abstract
Bioinformatic analysis of genomic sequencing data to identify somatic mutations in cancer samples is far from achieving the required robustness and standardisation. In this study we generated a whole exome sequencing benchmark dataset using the platinum genome sample NA12878 and developed an intersect-then-combine (ITC) approach to increase the accuracy in calling single nucleotide variants (SNVs) and indels in tumour-normal pairs. We evaluated the effect of alignment, base quality recalibration, mutation caller and filtering on sensitivity and false positive rate. The ITC approach increased the sensitivity up to 17.1%, without increasing the false positive rate per megabase (FPR/Mb) and its validity was confirmed in a set of clinical samples.
Sponsorship
Cancer Research UK (unknown)
Department of Health (via National Institute for Health Research (NIHR)) (unknown)
Cancer Research UK (60098573)
Cancer Research UK (unknown)
Cancer Research UK (CB4140)
Department of Health (via National Institute for Health Research (NIHR)) (NF-SI-0515-10090)
European Commission Horizon 2020 (H2020) Marie Sk?odowska-Curie actions (660060)
Cancer Research UK (A24622)
ECH2020 EUROPEAN RESEARCH COUNCIL (ERC) (694620)
EC FP7 CP (242006)
European Commission and European Federation of Pharmaceutical Industries and Associations (EFPIA) FP7 Innovative Medicines Initiative (IMI) (115749)
MRC (MR/P012442/1)
Cancer Research UK (20544)
EC FP7 CP (258967)
Cancer Research UK (C507/A16278)
European Commission FP7 Collaborative projects (CP) (258967)
Pathological Society of Great Britain & Ireland (CDF 2012/01)
Academy of Medical Sciences (ALI 01/08/14)
MEDICAL RESEARCH COUNCIL (MR/M008975/1)
Academy of Medical Sciences (unknown)
Cancer Research UK (16465)
Cambridge University Hospitals NHS Foundation Trust (CUH) (unknown)
European Commission FP7 Network of Excellence (NoE) (260791)
Cancer Research UK (A15580)
Cambridge University Hospitals NHS Foundation Trust (CUH) (RG51913)
EC FP7 NOE (260791)
WELLCOME TRUST (106566/Z/14/Z)
Identifiers
External DOI: https://doi.org/10.1186/s13073-017-0425-1
This record's URL: https://www.repository.cam.ac.uk/handle/1810/264082
Rights
Attribution 4.0 International, Attribution 4.0 International, Attribution 4.0 International, Attribution 4.0 International
Rights Holder: The Author(s).