BiomarkersThe path forward to highly sensitive and specific molecular diagnostics

Published September 2012 Updated September 2013 19 lectures
Dr. Charles Cantor
Sequenom Inc., USA

Biomarkers are molecules in clinical samples that have the potential to provide useful information about a person or an experimental organism. This can include the presence of disease, risk factors for developing a disease, evidence of response to a therapy, evidence of past or present exposure to an environmental agent,... read moreor other potentially useful phenotypes. An ideal biomarker can be measured in a sample of sputum, faeces or using various methods of lavage.

Recently interest in biomarkers has peaked because of great progress in the techniques for discovering such markers, validating them in clinical populations, and ultimately converting these markers into diagnostic tests. Biomarkers are showing increasing utility in selecting optimal populations for clinical trials and in serving as surrogate endpoints for these trials. Biomarkers can be qualitative, as in the detection of a mutation that informs about potential responsiveness to a focused therapeutic agent, or quantitative as in the levels of expression of sets of genes with prognostic value.

Currently the most actively pursued biomarkers are biological macromolecules. Nucleic acids are particularly convenient as biomarkers because of our ability to amplify them in vitro by the polymerase chain reaction and related techniques. Proteins are most easily studied by immunoassays or by mass spectrometry combined with high resolution separation techniques. Variations on these methods look at epigenetic changes in DNA (methylation), post-transcriptional changes in RNA and post-translational changes in proteins like glycosylation. Lipids and small molecules are also potentially interesting sources of biomarkers.

Generally biomarker discovery can now be carried out on a hypothesis free genome wide basis leading to terms like genomics, epigenomics, proteomics, glycomics, lipidomics and metabolomics. These methods are usually too costly for large clinical studies and often too complex for mature diagnostics. Thus genome wide studies are inevitably followed by more focused studies on simpler and often more quantitative platforms. Besides the usual criteria of specificity and sensitivity, dynamic range is a major concern for many types of biomarkers.