Sample-Index Misassignment Impacts Tumour Exome Sequencing

Sample pooling enabled by dedicated indexes is a common strategy for cost-effective and robust high-throughput sequencing. Index misassignment leading to mutual contamination between pooled samples has however been described as a general problem of the latest Illumina sequencing instruments utilizin...

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Bibliographic Details
Published in:Scientific reports 2018-03, Vol.8 (1), p.5307-6, Article 5307
Main Authors: Vodák, Daniel, Lorenz, Susanne, Nakken, Sigve, Aasheim, Lars Birger, Holte, Harald, Bai, Baoyan, Myklebost, Ola, Meza-Zepeda, Leonardo A., Hovig, Eivind
Format: Article
Language:English
Subjects:
45/23
631/61/514/2254
631/67/69
Algorithms
Alleles
Cancer
Consortia
Contamination
Data Accuracy
Exome - genetics
Exome Sequencing - methods
Experiments
Gene Frequency - genetics
Gene Library
Genomics
High-Throughput Nucleotide Sequencing - methods
Humanities and Social Sciences
Humans
Informatics
Lymphoma
Medical research
multidisciplinary
Neoplasms
Next-generation sequencing
Sarcoma
Science
Science (multidisciplinary)
Sequence Analysis, DNA - methods
Software
Tumors
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Summary:Sample pooling enabled by dedicated indexes is a common strategy for cost-effective and robust high-throughput sequencing. Index misassignment leading to mutual contamination between pooled samples has however been described as a general problem of the latest Illumina sequencing instruments utilizing exclusion amplification. Using real-life data from multiple tumour sequencing projects, we demonstrate that index misassignment can induce artefactual variant calls closely resembling true, high-quality somatic variants. These artefactual calls potentially impact cancer applications utilizing low allelic frequencies, such as in clonal analysis of tumours. We discuss the available countermeasures with an emphasis on improved library indexing methods, and provide software that can assist in the identification of variants that may be consequences of index misassignment.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-018-23563-4