title: Prior knowledge transfer across transcriptional data sets and technologies using compositional statistics yields new mislabelled ovarian cell line.
abstract: Here, we describe gene expression compositional assignment (GECA), a powerful, yet simple method based on compositional statistics that can validate the transfer of prior knowledge, such as gene lists, into independent data sets, platforms and technologies. Transcriptional profiling has been used to derive gene lists that stratify patients into prognostic molecular subgroups and assess biomarker performance in the pre-clinical setting. Archived public data sets are an invaluable resource for subsequent in silico validation, though their use can lead to data integration issues. We show that GECA can be used without the need for normalising expression levels between data sets and can outperform rank-based correlation methods. To validate GECA, we demonstrate its success in the cross-platform transfer of gene lists in different domains including: bladder cancer staging, tumour site of origin and mislabelled cell lines. We also show its effectiveness in transferring an epithelial ovarian cancer prognostic gene signature across technologies, from a microarray to a next-generation sequencing setting. In a final case study, we predict the tumour site of origin and histopathology of epithelial ovarian cancer cell lines. In particular, we identify and validate the commonly-used cell line OVCAR-5 as non-ovarian, being gastrointestinal in origin. GECA is available as an open-source R package.
authors.affiliation: Centre for Cancer Research and Cell Biology, Queen's University, Belfast, BT9 7BL, UK j.blayney@qub.ac.uk.
authors.forename: Jaine K
authors.initials: JK
authors.lastname: Blayney
authors.affiliation: Centre for Cancer Research and Cell Biology, Queen's University, Belfast, BT9 7BL, UK Almac Diagnostics, Craigavon, BT63 5QD, UK.
authors.forename: Timothy
authors.initials: T
authors.lastname: Davison
authors.affiliation: Centre for Cancer Research and Cell Biology, Queen's University, Belfast, BT9 7BL, UK Almac Diagnostics, Craigavon, BT63 5QD, UK.
authors.forename: Nuala
authors.initials: N
authors.lastname: McCabe
authors.affiliation: Centre for Cancer Research and Cell Biology, Queen's University, Belfast, BT9 7BL, UK Almac Diagnostics, Craigavon, BT63 5QD, UK.
authors.forename: Steven
authors.initials: S
authors.lastname: Walker
authors.affiliation: Almac Diagnostics, Craigavon, BT63 5QD, UK.
authors.forename: Karen
authors.initials: K
authors.lastname: Keating
authors.affiliation: Almac Diagnostics, Craigavon, BT63 5QD, UK.
authors.forename: Thomas
authors.initials: T
authors.lastname: Delaney
authors.affiliation: Centre for Cancer Research and Cell Biology, Queen's University, Belfast, BT9 7BL, UK Almac Diagnostics, Craigavon, BT63 5QD, UK.
authors.forename: Caroline
authors.initials: C
authors.lastname: Greenan
authors.affiliation: Department of Pathology, The University of Edinburgh, Royal Infirmary of Edinburgh, EH16 4SA, UK.
authors.forename: Alistair R
authors.initials: AR
authors.lastname: Williams
authors.affiliation: Centre for Cancer Research and Cell Biology, Queen's University, Belfast, BT9 7BL, UK Department of Pathology, Belfast Health and Social Care Trust, Belfast, BT12 6BA, UK.
authors.forename: W Glenn
authors.initials: WG
authors.lastname: McCluggage
authors.affiliation: CellBank Australia, Children's Medical Research Institute, University of Sydney, Westmead, NSW, Australia.
authors.forename: Amanda
authors.initials: A
authors.lastname: Capes-Davis
authors.affiliation: Centre for Cancer Research and Cell Biology, Queen's University, Belfast, BT9 7BL, UK Almac Diagnostics, Craigavon, BT63 5QD, UK.
authors.forename: D Paul
authors.initials: DP
authors.lastname: Harkin
authors.affiliation: Edinburgh Cancer Research Centre, The University of Edinburgh, Western General Hospital, Edinburgh, EH4 2XR, UK.
authors.forename: Charlie
authors.initials: C
authors.lastname: Gourley
authors.affiliation: Centre for Cancer Research and Cell Biology, Queen's University, Belfast, BT9 7BL, UK Almac Diagnostics, Craigavon, BT63 5QD, UK.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Kennedy
mesh_terms: D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D030541:Databases, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D013194:Staining and Labeling; D013223:Statistics as Topic; D014158:Transcription, Genetic