Functional molecular units for guiding biomarker panel design

Abstract

The field of biomarker research has experienced a major boost in recent years, and the number of publications on biomarker studies evaluating given, but also proposing novel biomarker candidates is increasing rapidly for numerous clinically relevant disease areas. However, individual markers often lack sensitivity and specifi city in the clinical context, resting essentially on the intra-individual phenotype variability hampering sensitivity, or on assessing more general processes downstream of the causative molecular events characterizing a disease term, in consequence impairing disease specifi city. The trend to circumvent these shortcomings goes towards utilizing multimarker panels, thus combining the strength of individual markers to further enhance performance regarding both sensitivity and specifi city. A way of identifying the optimal composition of individual markers in a panel approach is to pick each marker as representative for a specifi c pathophysiological (mechanistic) process relevant for the disease under investigation, hence resulting in a multimarker panel for covering the set of pathophysiological processes underlying the frequently multifactorial composition of a clinical phenotype. Here we outline a procedure of identifying such sets of disease-specifi c pathophysiological processes (units) delineated on the basis of disease-associated molecular feature lists derived from literature mining as well as aggregated, publicly available Omics profi ling experiments. With such molecular units in hand, providing an improved refl ection of a specifi c clinical phenotype, biomarker candidates can then be assigned to or novel candidates are to be selected from these units, subsequently resulting in a multimarker panel promising improved accuracy in disease diagnosis as well as prognosis.