title: Detect tissue heterogeneity in gene expression data with BioQC.
abstract: Gene expression data can be compromised by cells originating from other tissues than the target tissue of profiling. Failures in detecting such tissue heterogeneity have profound implications on data interpretation and reproducibility. A computational tool explicitly addressing the issue is warranted.
  
  
  
  We introduce BioQC, a R/Bioconductor software package to detect tissue heterogeneity in gene expression data. To this end BioQC implements a computationally efficient Wilcoxon-Mann-Whitney test and provides more than 150 signatures of tissue-enriched genes derived from large-scale transcriptomics studies. Simulation experiments show that BioQC is both fast and sensitive in detecting tissue heterogeneity. In a case study with whole-organ profiling data, BioQC predicted contamination events that are confirmed by quantitative RT-PCR. Applied to transcriptomics data of the Genotype-Tissue Expression (GTEx) project, BioQC reveals clustering of samples and suggests that some samples likely suffer from tissue heterogeneity.
  
  
  
  Our experience with gene expression data indicates a prevalence of tissue heterogeneity that often goes unnoticed. BioQC addresses the issue by integrating prior knowledge with a scalable algorithm. We propose BioQC as a first-line tool to ensure quality and reproducibility of gene expression data.
authors.affiliation: Roche Pharma Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, Basel, 4070, Switzerland. jitao_david.zhang@roche.com.
authors.forename: Jitao David
authors.identifier: http://orcid.org/0000-0002-3085-0909
authors.initials: JD
authors.lastname: Zhang
authors.affiliation: Roche Pharma Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, Basel, 4070, Switzerland.
authors.forename: Klas
authors.initials: K
authors.lastname: Hatje
authors.affiliation: Roche Pharma Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, Basel, 4070, Switzerland.
authors.forename: Gregor
authors.initials: G
authors.lastname: Sturm
authors.affiliation: Roche Pharma Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, Basel, 4070, Switzerland.|, Present address: Peter-Rot-Strasse 84, Basel, 4058, Switzerland.
authors.forename: Clemens
authors.initials: C
authors.lastname: Broger
authors.affiliation: Roche Pharma Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, Basel, 4070, Switzerland.
authors.forename: Martin
authors.initials: M
authors.lastname: Ebeling
authors.affiliation: Inserm U1151, Université Paris Descartes, Institut Necker Enfants Malades, Hôpital Necker Enfants Malades, 149, Rue de Sèvres, Paris, 75015, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Burtin
authors.affiliation: Inserm U1151, Université Paris Descartes, Institut Necker Enfants Malades, Hôpital Necker Enfants Malades, 149, Rue de Sèvres, Paris, 75015, France.
authors.forename: Fabiola
authors.initials: F
authors.lastname: Terzi
authors.affiliation: Roche Pharma Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, Basel, 4070, Switzerland.
authors.forename: Silvia Ines
authors.initials: SI
authors.lastname: Pomposiello
authors.affiliation: Roche Pharma Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, Basel, 4070, Switzerland.
authors.forename: Laura
authors.initials: L
authors.lastname: Badi
mesh_terms: D000465:Algorithms; D000818:Animals; D004285:Dogs; D020869:Gene Expression Profiling; D006801:Humans; D051379:Mice; D009928:Organ Specificity; D015203:Reproducibility of Results; D012984:Software; D059467:Transcriptome
keywords: Gene expression; Gene-set enrichment analysis; Quality control; Wilcoxon-Mann-Whitney test