title: SeqControl: process control for DNA sequencing.
abstract: As high-throughput sequencing continues to increase in speed and throughput, routine clinical and industrial application draws closer. These 'production' settings will require enhanced quality monitoring and quality control to optimize output and reduce costs. We developed SeqControl, a framework for predicting sequencing quality and coverage using a set of 15 metrics describing overall coverage, coverage distribution, basewise coverage and basewise quality. Using whole-genome sequences of 27 prostate cancers and 26 normal references, we derived multivariate models that predict sequencing quality and depth. SeqControl robustly predicted how much sequencing was required to reach a given coverage depth (area under the curve (AUC) = 0.993), accurately classified clinically relevant formalin-fixed, paraffin-embedded samples, and made predictions from as little as one-eighth of a sequencing lane (AUC = 0.967). These techniques can be immediately incorporated into existing sequencing pipelines to monitor data quality in real time. SeqControl is available at http://labs.oicr.on.ca/Boutros-lab/software/SeqControl/.
authors.affiliation: Informatics &Biocomputing Platform, Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
authors.forename: Lauren C
authors.initials: LC
authors.lastname: Chong
authors.affiliation: Informatics &Biocomputing Platform, Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
authors.forename: Marco A
authors.initials: MA
authors.lastname: Albuquerque
authors.affiliation: Informatics &Biocomputing Platform, Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Harding
authors.affiliation: Informatics &Biocomputing Platform, Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
authors.forename: Cristian
authors.initials: C
authors.lastname: Caloian
authors.affiliation: Informatics &Biocomputing Platform, Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
authors.forename: Michelle
authors.initials: M
authors.lastname: Chan-Seng-Yue
authors.affiliation: Informatics &Biocomputing Platform, Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
authors.forename: Richard
authors.initials: R
authors.lastname: de Borja
authors.affiliation: Department of Pathology, University Health Network, Toronto, Ontario, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Fraser
authors.affiliation: Informatics &Biocomputing Platform, Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Denroche
authors.affiliation: Informatics &Biocomputing Platform, Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
authors.forename: Timothy A
authors.identifier: 0000000301453557
authors.initials: TA
authors.lastname: Beck
authors.affiliation: Department of Pathology, University Health Network, Toronto, Ontario, Canada.
authors.forename: Theodorus
authors.initials: T
authors.lastname: van der Kwast
authors.affiliation: 1] Ontario Cancer Institute, University Health Network, Toronto, Ontario, Canada. [2] Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Bristow
authors.affiliation: 1] Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada. [2] Genomics Platform, Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
authors.forename: John D
authors.initials: JD
authors.lastname: McPherson
authors.affiliation: 1] Informatics &Biocomputing Platform, Ontario Institute for Cancer Research, Toronto, Ontario, Canada. [2] Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada. [3] Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Paul C
authors.identifier: 0000000305537520
authors.initials: PC
authors.lastname: Boutros
mesh_terms: D000465:Algorithms; D019540:Area Under Curve; D019295:Computational Biology / Q000379:methods*; D016678:Genome; D005838:Genotype; D006801:Humans; D016014:Linear Models; D008297:Male; D015999:Multivariate Analysis; D011471:Prostatic Neoplasms / Q000378:metabolism*; D011786:Quality Control; D017422:Sequence Analysis, DNA / Q000379:methods*; D012984:Software