Biomarker discovery
Biomarker discovery is a medical term describing the process by which biomarkers are discovered. Many commonly used blood tests in medicine are biomarkers. There is interest in biomarker discovery on the part of the pharmaceutical industry; blood-test or other biomarkers could serve as intermediate markers of disease in clinical trials, and as possible drug targets.
Mechanism of action
The way that these tests have been found can be viewed as biomarker discovery; however, their identification has primarily been made one at a time. Many well-known tests have been identified based on biological insight from the fields of physiology or biochemistry; therefore, only a few markers at a time have been considered. An example of biomarker discovery is the use of inulin to assess kidney function. From this process a naturally occurring molecule (creatinine) was discovered, enabling the same measurements to be made without insulin injections.
The recent interest in biomarker discovery is spurred by new molecular biologic techniques, which promise to find relevant markers rapidly without detailed insight into the mechanisms of a disease. By screening many possible biomolecules at a time, a parallel approach can be attempted; genomics and proteomics are some technologies used in this process. Secretomics has also emerged as an important technology in the high-throughput search for biomarkers;[1] however, significant technical difficulties remain.
The identification of clinically significant protein
Biofluids contain proteins from tissues and serve as effective hormonal communicators. The tissue acts as a transmitter of information, and the biofluid (sampled by physician) acts as a receiver. The informativeness of the biofluid relies on the fidelity of the channel. Sources of noise which decrease fidelity include the addition of proteins derived from other tissues (or from the biofluid itself); proteins may also be lost through
Instead, the proteins' projection onto functional, drug, and disease spaces allow measurement of the functional distance between tissue and biofluids. Proximity in these abstract spaces signifies a low level of distortion across the information channel (and, hence, high performance by the biofluid). However, current approaches to biomarker prediction have analyzed tissues and biofluids separately.[6]
Methods of discovery
Genomic approach
There are four major methods for genomic analysis. First, a northern blot can be used to isolate a set of RNA sequences. Second and third, they can be analyzed by standard Gene expression techniques, or surveyed using SAGE. Lastly, a DNA microarray[7] measurement can be taken, to determine the frequency of each gene; this information can be used to determine whether a gene is a biomarker.
Often, a polymerase chain reaction is used to create many copies of the sequences to make them easier to work with. In February 2016, Dr. Laura Elnitski and company used this technique to detect a biomarker shared by five types of cancer.[8]
Proteomic approach
Proteomic methods are an effective tool for analysis of biomarkers with advantages including fast and accurate screening for diseases in, for example, blood serum. Common proteomic techniques for biomarkers includes:[9]
Metabolomic approach
The term
Lipidomics approach
Glycomics approach
Glycosylation is a common posttranslational protein modifications, and almost all cell surface and secreted proteins are modified by covalently-linked carbohydrates. Eukaryotic glycans are generally classified into two main groups: N- and O-glycans, where the glycan chains are linked to asparagine and serine/threonine residues, respectively. Glycans are essential mediators of biological processes such as protein folding, cell signalling, fertilization, embryogenesis, neuronal development, hormone activity and the proliferation of cells and their organization into specific tissues. In addition, overwhelming data supports the relevance of glycosylation in pathogen recognition, inflammation, innate immune responses, and the development of autoimmune diseases and cancer. However, the identification of these biomarkers has not been easy, mainly due to the structural diversity and numerous possible glycan isomers. Fortunately, glycomics is becoming more feasible due to major improvements in mass spectrometry and separation science.[10]
Ex vivo blood stimulation
Ex vivo blood stimulation is the process by which researchers can analyse the immunological biomarkers of drug effects in healthy volunteers. Blood samples (taken from healthy volunteers) are stimulated in the laboratory to activate the immune system. Ex vivo blood stimulation studies, therefore, allow the evaluation of the effect of a new compound in a "living system" in which the immune system has been challenged.[11] Most research using this method is carried out by Phase I clinical research organisations, allowing them to collect blood samples and analyse them instantly so they do not deteriorate.
See also
- Biomarker
- Biomarker (medicine)
- Clinical chemistry
- Clinical proteomics
- Drug discovery
- Genomics
- Proteomics
- Secretomics
- Endophenotype
- Massive parallel sequencing
References
- PMID 17425459.
- PMID 17341705.
- PMID 17101857.
- PMID 16083256.
- PMID 12488461.
- PMID 17192065.
- PMID 17233815.
- ^ "NIH Researchers Identify Striking Genomic Signature Shared by 5 Types of Cancer - ScienceNewsline". www.sciencenewsline.com. Retrieved 2016-04-24.[permanent dead link]
- ISSN 0003-2654.
- .
- ^ "Ex Vivo Blood Stimulation in Biomarker Discovery". Archived from the original on 2009-11-29. Retrieved 2009-10-23.
External links
- Liotta, Lance A.; Ferrari, Mauro; Petricoin, Emanuel (2003). "Clinical proteomics: Written in blood" (PDF). Nature. 425 (6961): 905. PMID 14586448.
- "NIH National Cancer Institute. Questions and Answers: Proteomics and Cancer". 1980-01-01. Retrieved 2006-04-05.
- Howard Schulman. "The Hottest New Term in Biotech" (PDF). Archived from the original (PDF) on 2006-11-13. Retrieved 2006-11-29.
- "Biomarket Trends: Molecular Diagnostics on the Move". Genetic Engineering & Biotechnology News.
- "Capitalizing on Biomarker Discovery Work". Genetic Engineering & Biotechnology News.
- Enrique A. Dalmasso (2008-06-15). "Planning for Success in Biomarker Discovery". Mary Ann Liebert, Inc.pp. 28–30. Retrieved 2008-07-06.
(subtitle) Appropriate proteomics platform and careful study design can improve positive results
- "High Risk Plaque Blood Biomarker Discovery Study". 2007. Retrieved 2011-08-22.
- Academic journals in the field