A biomarker, as defined by the National Cancer Institute, is a biological molecule found in blood, other bodily fluids, or tissues that is a sign of a normal or abnormal process — or of a condition or disease. They are analytically measurable, are generally predictive, and have a variety of uses, from determining someone’s risk for stroke to measuring the progress of a disease. To determine the significance of a biomarker associated with a physiological condition, there’s a process that expands from initial discovery to characterization, and then to pre-clinical and clinical validation.
The steps taken during the analytical phase are dependent on the type of biomarker, which can range from DNA, RNA, protein, peptide, biomolecular modification(s), or biochemical pathway(s). Assay technologies are used during the process of analytical evaluation and validation of biomarkers. Here is a brief overview of the steps of the biomarker discovery process:
Biomarker sample or study design
As the first step in the project, the origin sample or biospecimen is a critical factor in deciding the durability and reproducibility of the study. It must be accompanied with appropriate annotations, as well as methods for sample preparation. The work done in this stage will impact the identification and future characterization of biomarkers.
Next, data is published on the biomarkers at a genetic level. Using prior studies, you can obtain single or multiple genes that encode the protein biomarker(s) and establish a foundation for your biomarker identification. If limited genetic data is attainable, technology is available (like next-generation sequencing) to identify and characterize genes.
The data generated at the molecular and phenotype level of biomarker characterization requires appropriate annotation and analysis tools.
Biomarker characterization and validation
A key to biomarker discovery and characterization is the determination of molecular size and structure of protein biomarkers. To do this, various analytical platforms such as chromatography and mass spectrometry are performed. At this point, biomarkers are associated with a disease or physiological state. This is determined using subcellular localization, high-content analysis, and in-vivo studies within animal model systems. .
For clinical validation, the test must reliably correlate with the phenotype or outcome of interest. The development of cutting-edge technologies at the single-cell level will enhance the legitimacy and relevance of biomarkers with clinical phenotype..
To learn more about the challenges, bottlenecks, and common mistakes of biomarker discovery — as well as optimal strategies — please continue reading.