title: Pan-cancer analysis of systematic batch effects on somatic sequence variations.
abstract: BACKGROUND
  The 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.
  
  
  RESULTS
  We 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.
  
  
  CONCLUSIONS
  Our strategy for identifying batch-biased variants and characterising sequence patterns might be useful in eliminating false variants and facilitating correct interpretation of sequence profiles.
authors.affiliation: 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.
authors.forename: Ji-Hye
authors.initials: JH
authors.lastname: Choi
authors.affiliation: Department of Physiology, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon, South Korea.
authors.forename: Seong-Eui
authors.initials: SE
authors.lastname: Hong
authors.affiliation: Department of Physiology, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon, South Korea. hg@ajou.ac.kr.|Department of Biomedical Science, Graduate School, Ajou University, Suwon, South Korea. hg@ajou.ac.kr.
authors.forename: Hyun Goo
authors.identifier: http://orcid.org/0000-0002-0916-893X
authors.initials: HG
authors.lastname: Woo
mesh_terms: D030541:Databases, Genetic; D023281:Genomics / Q000379:methods*; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D015203:Reproducibility of Results; D017422:Sequence Analysis, DNA
keywords: Batch effect; Mutation; Pan-cancer; TCGA