title: A hypothesis-directed approach to the targeted development of a multiplexed proteomic biomarker assay for cancer.
abstract: In recent years, hundreds of candidate protein biomarkers have been identified using discovery-based proteomics. Despite the large number of candidate biomarkers, few proteins advance to clinical validation. We propose a hypothesis-driven approach to identify candidate biomarkers, previously characterized in the literature, with the highest probability of clinical applicability. A ranking method, called the "hypothesis-directed biomarker ranking" (HDBR) system, was developed to score candidate biomarkers based on seven criteria deemed important in the selection of clinically useful biomarkers. To demonstrate its application, we applied the HDBR system to identify candidate biomarkers for the development of a diagnostic test for the early detection of colorectal cancer. One-hundred and fifty-one candidate biomarkers were identified from the literature and ranked based on the specified criteria. The top-ranked candidates represent a group of biomarkers whose further study and validation would be justified in order to expedite the development of biomarkers that could be used in a clinical setting.
authors.affiliation: Department of Medical Sciences, University of Calgary, Calgary, AB, Canada.
authors.forename: Emily M
authors.initials: EM
authors.lastname: Mackay
authors.affiliation: Department of Medical Sciences, University of Calgary, Calgary, AB, Canada.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Koppel
authors.affiliation: Department of Medical Sciences, University of Calgary, Calgary, AB, Canada.
authors.forename: Pooja
authors.initials: P
authors.lastname: Das
authors.affiliation: Department of Medical Sciences, University of Calgary, Calgary, AB, Canada.
authors.forename: Joanna
authors.initials: J
authors.lastname: Woo
authors.affiliation: Department of Chemistry, University of Calgary, Calgary, AB, Canada.
authors.forename: David C
authors.initials: DC
authors.lastname: Schriemer
authors.affiliation: Department of Surgery, University of Calgary, Calgary, AB, Canada. ; Department of Oncology, University of Calgary, Calgary, AB, Canada.
authors.forename: Oliver F
authors.initials: OF
authors.lastname: Bathe
keywords: biomarker; colorectal cancer; diagnosis; targeted proteomics