Single-Patient Molecular Testing with NanoString nCounter Data Using a Reference-Based Strategy for Batch Effect Correction.
A major weakness in many high-throughput genomic studies is the lack of consideration of a clinical environment where one patient at a time must be evaluated. We examined generalizable and platform-specific sources of variation from NanoString gene expression data on both ovarian cancer and Hodgkin lymphoma patients. A reference-based strategy, applicable to single-patient molecular testing is proposed for batch effect correction. The proposed protocol improved performance in an established Hodgkin lymphoma classifier, reducing batch-to-batch misclassification while retaining accuracy and precision. We suggest this strategy may facilitate development of NanoString and similar molecular assays by accelerating prospective validation and clinical uptake of relevant diagnostics.
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada.
Aline
A
Talhouk
Department of Women's Health, University Hospital Tuebingen, Tuebingen, Germany.
Stefan
S
Kommoss
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada.
Robertson
R
Mackenzie
British Columbia Centre for Disease Control, Vancouver, Canada.
Martin
M
Cheung
Genetic Pathology Evaluation Centre (GPEC), Vancouver General Hospital and The University of British Columbia, Vancouver, Canada.
Samuel
S
Leung
Department of Statistics, University of British Columbia, Vancouver, Canada.
Derek S
DS
Chiu
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada.|Pancreas Centre BC, Vancouver, Canada.
Steve E
SE
Kalloger
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada.|Genetic Pathology Evaluation Centre (GPEC), Vancouver General Hospital and The University of British Columbia, Vancouver, Canada.|Department of Obstetrics and Gynaecology, University of British Columbia, Vancouver, Canada.
David G
DG
Huntsman
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, United States of America.
Stephanie
S
Chen
School of Women's and Children's Health, University of New South Wales, Sydney, NSW, Australia.
Maria
M
Intermaggio
Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland.
Jacek
J
Gronwald
Centre for Lymphoid Cancer, British Columbia Cancer Agency Cancer Research Centre, Vancouver, Canada.
Fong C
FC
Chan
School of Women's and Children's Health, University of New South Wales, Sydney, NSW, Australia.|The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.
Susan J
SJ
Ramus
Centre for Lymphoid Cancer, British Columbia Cancer Agency Cancer Research Centre, Vancouver, Canada.
Christian
C
Steidl
Centre for Lymphoid Cancer, British Columbia Cancer Agency Cancer Research Centre, Vancouver, Canada.
David W
DW
Scott
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada.|Department of Obstetrics and Gynaecology, University of British Columbia, Vancouver, Canada.
Michael S
MS
Anglesio
D016477:Artifacts; D015331:Cohort Studies; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods* / Q000592:standards*; D023281:Genomics; D006689:Hodgkin Disease / Q000235:genetics; D006801:Humans; D010051:Ovarian Neoplasms / Q000235:genetics; D012015:Reference Standards