Pan-cancer analysis of systematic batch effects on somatic sequence variations

BMC Bioinformatics

Research Article

Seong-Eui Hong¹  Hyun Goo Woo²  Ji-Hye Choi² 

[1] Department of Physiology, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon, South Korea;Department of Physiology, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon, South Korea;Department of Biomedical Science, Graduate School, Ajou University, Suwon, South Korea;

关键词: Batch effect;    TCGA;    Pan-cancer;    Mutation;   

DOI  :  10.1186/s12859-017-1627-7

 received in 2016-12-13, accepted in 2017-04-06,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundThe Cancer Genome Atlas (TCGA) is a comprehensive database that includes multi-layered cancer genome profiles. Large-scale collection of data inevitably generates batch effects introduced by differences in processing at various stages from sample collection to data generation. However, batch effects on the sequence variation and its characteristics have not been studied extensively.ResultsWe systematically evaluated batch effects on somatic sequence variations in pan-cancer TCGA data, revealing 999 somatic variants that were batch-biased with statistical significance (P < 0.00001, Fisher’s exact test, false discovery rate ≤ 0.0027). Most of the batch-biased variants were associated with specific sample plates. The batch-biased variants, which had a unique mutational spectrum with frequent indel-type mutations, preferentially occurred at sites prone to sequencing errors, e.g., in long homopolymer runs. Non-indel type batch-biased variants were frequent at splicing sites with the unique consensus motif sequence ‘TTDTTTAGTT’. Furthermore, some batch-biased variants occur in known cancer genes, potentially causing misinterpretation of mutation profiles.ConclusionsOur strategy for identifying batch-biased variants and characterising sequence patterns might be useful in eliminating false variants and facilitating correct interpretation of sequence profiles.

【 授权许可】

CC BY   
© The Author(s). 2017