Biomarker discovery
Encyclopedia
Biomarker discovery is the process by which biomarker
s are discovered. It is a medical term.
Many commonly used blood test
s in medicine are biomarkers. The way that these tests have been found can be seen as biomarker discovery. However, their identification has mostly been a one-at-a time approach. Many of these well-known tests have been identified based on clear biological insight, from physiology
or biochemistry
. This means that only a few markers at a time have been considered. One example of this way of biomarker discovery is the use of injections of inulin
for measuring kidney function. From this, one discovered a naturally occurring molecule, creatinine
, that enabled the same measurements to be made easily without injections. This can be seen as a serial process.
The recent interest in biomarker discovery is because new molecular biologic
techniques promise to find relevant markers rapidly, without detailed insight into mechanisms of disease. By screening many possible biomolecule
s at a time, a parallel approach can be tried. Genomics
and proteomics
are some technologies that are used in this process. Secretomics
has also emerged as an important technology in the high-throughput search for biomarkers. Significant technical difficulties remain.
There is considerable interest in biomarker discovery from the pharmaceutical industry. Blood test or other biomarkers could serve as intermediate markers of disease in clinical trials, and also be possible drug targets
.
Identification of clinically significant protein biomarkers
of phenotype
and biological function is an expanding area of research that will extend diagnostic capabilities. Recently, biomarkers for various diseases have emerged, including prostate specific antigen
(PSA) for prostate cancer
and C-reactive protein
(CRP) for heart disease. Using biomarkers from easily assessable biofluids (e.g. blood, urine) is beneficial in evaluating the state of harder-to-reach tissues and organs. Biofluids are much more readily accessible, unlike more invasive or unfeasible techniques such as tissue biopsies.
Biofluids contain proteins from tissues and serve as effective communication/hormonal. The tissue acts as a transmitter of information and the biofluid (sampled by physician) as a receiver. The informativeness of the biofluid relies on the fidelity of the channel. Sources of noise that decrease fidelity include addition of proteins derived from other tissues or from the biofluid itself; proteins may also be lost through the glomerular filtration process. These factors can significantly bias the protein composition of a biofluid. In addition, simply looking at protein overlap would miss information transmission that occurs through classes of proteins and protein-protein interactions.
Instead, the proteins projection onto functional, drug, and disease spaces are considered to allow the measurement of functional distance between tissue and biofluids. Closeness in these abstract spaces signifies a low level of distortion across the information channel, and hence high performance of the biofluid. However, current approaches to biomarker prediction have analyzed tissues and biofluids separately.
between certain biofluids and tissues with the potential for clinically significant findings, not possible if tissues and biofluids were considered individually. By conceptualizing tissue-biofluid as information channels, significant biofluid proxies were identified and then used for guided development of clinical diagnostics. Candidate biomarkers were then predicted based on information transfer criteria across the tissue-biofluid channels. Significant biofluid-tissue relationships can be used to prioritize clinical validation of biomarkers.
blood stimulation is a process by which researchers can analyse the immunological biomarkers of drug-effect in healthy volunteers. Blood samples taken from normal 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. Most research using this method is carried out by Phase I clinical research organisations, allowing them to collect blood samples and analyse them instantly without degradation of the samples.
Biomarker (medicine)
In medicine, a biomarker is a term often used to refer to a protein measured in blood whose concentration reflects the severity or presence of some disease state...
s are discovered. It is a medical term.
Many commonly used blood test
Blood test
A blood test is a laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a needle, or via fingerprick....
s in medicine are biomarkers. The way that these tests have been found can be seen as biomarker discovery. However, their identification has mostly been a one-at-a time approach. Many of these well-known tests have been identified based on clear biological insight, from physiology
Physiology
Physiology is the science of the function of living systems. This includes how organisms, organ systems, organs, cells, and bio-molecules carry out the chemical or physical functions that exist in a living system. The highest honor awarded in physiology is the Nobel Prize in Physiology or...
or biochemistry
Biochemistry
Biochemistry, sometimes called biological chemistry, is the study of chemical processes in living organisms, including, but not limited to, living matter. Biochemistry governs all living organisms and living processes...
. This means that only a few markers at a time have been considered. One example of this way of biomarker discovery is the use of injections of inulin
Inulin
Inulins are a group of naturally occurring polysaccharides produced by many types of plants. They belong to a class of fibers known as fructans. Inulin is used by some plants as a means of storing energy and is typically found in roots or rhizomes...
for measuring kidney function. From this, one discovered a naturally occurring molecule, creatinine
Creatinine
Creatinine is a break-down product of creatine phosphate in muscle, and is usually produced at a fairly constant rate by the body...
, that enabled the same measurements to be made easily without injections. This can be seen as a serial process.
The recent interest in biomarker discovery is because new molecular biologic
Molecular biology
Molecular biology is the branch of biology that deals with the molecular basis of biological activity. This field overlaps with other areas of biology and chemistry, particularly genetics and biochemistry...
techniques promise to find relevant markers rapidly, without detailed insight into mechanisms of disease. By screening many possible biomolecule
Biomolecule
A biomolecule is any molecule that is produced by a living organism, including large polymeric molecules such as proteins, polysaccharides, lipids, and nucleic acids as well as small molecules such as primary metabolites, secondary metabolites, and natural products...
s at a time, a parallel approach can be tried. Genomics
Genomics
Genomics is a discipline in genetics concerning the study of the genomes of organisms. The field includes intensive efforts to determine the entire DNA sequence of organisms and fine-scale genetic mapping efforts. The field also includes studies of intragenomic phenomena such as heterosis,...
and proteomics
Proteomics
Proteomics is the large-scale study of proteins, particularly their structures and functions. Proteins are vital parts of living organisms, as they are the main components of the physiological metabolic pathways of cells. The term "proteomics" was first coined in 1997 to make an analogy with...
are some technologies that are used in this process. Secretomics
Secretomics
Secretomics is a subset of proteomics in which all of the secreted proteins of a cell, tissue, or organism are analyzed. Secreted proteins are involved in a variety of physiological processes, including cell signaling and matrix remodeling, but are also integral to invasion and metastasis of...
has also emerged as an important technology in the high-throughput search for biomarkers. Significant technical difficulties remain.
There is considerable interest in biomarker discovery from the pharmaceutical industry. Blood test or other biomarkers could serve as intermediate markers of disease in clinical trials, and also be possible drug targets
Drug discovery
In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which drugs are discovered or designed.In the past most drugs have been discovered either by identifying the active ingredient from traditional remedies or by serendipitous discovery...
.
Identification of clinically significant protein biomarkers
Biomarker (medicine)
In medicine, a biomarker is a term often used to refer to a protein measured in blood whose concentration reflects the severity or presence of some disease state...
of phenotype
Phenotype
A phenotype is an organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior...
and biological function is an expanding area of research that will extend diagnostic capabilities. Recently, biomarkers for various diseases have emerged, including prostate specific antigen
Prostate specific antigen
Prostate-specific antigen also known as gamma-seminoprotein or kallikrein-3 is a glycoprotein that in humans is encoded by the KLK3 gene. KLK3 is a member of the kallikrein-related peptidase family that are secreted by the epithelial cells of the prostate gland...
(PSA) for prostate cancer
Prostate cancer
Prostate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system. Most prostate cancers are slow growing; however, there are cases of aggressive prostate cancers. The cancer cells may metastasize from the prostate to other parts of the body, particularly...
and C-reactive protein
C-reactive protein
C-reactive protein is a protein found in the blood, the levels of which rise in response to inflammation...
(CRP) for heart disease. Using biomarkers from easily assessable biofluids (e.g. blood, urine) is beneficial in evaluating the state of harder-to-reach tissues and organs. Biofluids are much more readily accessible, unlike more invasive or unfeasible techniques such as tissue biopsies.
Biofluids contain proteins from tissues and serve as effective communication/hormonal. The tissue acts as a transmitter of information and the biofluid (sampled by physician) as a receiver. The informativeness of the biofluid relies on the fidelity of the channel. Sources of noise that decrease fidelity include addition of proteins derived from other tissues or from the biofluid itself; proteins may also be lost through the glomerular filtration process. These factors can significantly bias the protein composition of a biofluid. In addition, simply looking at protein overlap would miss information transmission that occurs through classes of proteins and protein-protein interactions.
Instead, the proteins projection onto functional, drug, and disease spaces are considered to allow the measurement of functional distance between tissue and biofluids. Closeness in these abstract spaces signifies a low level of distortion across the information channel, and hence high performance of the biofluid. However, current approaches to biomarker prediction have analyzed tissues and biofluids separately.
Research
An information theoretic framework for biomarker discovery, integrating biofluid and tissue information, has been introduced and this new approach takes advantage of functional synergySynergy
Synergy may be defined as two or more things functioning together to produce a result not independently obtainable.The term synergy comes from the Greek word from , , meaning "working together".-Definitions and usages:...
between certain biofluids and tissues with the potential for clinically significant findings, not possible if tissues and biofluids were considered individually. By conceptualizing tissue-biofluid as information channels, significant biofluid proxies were identified and then used for guided development of clinical diagnostics. Candidate biomarkers were then predicted based on information transfer criteria across the tissue-biofluid channels. Significant biofluid-tissue relationships can be used to prioritize clinical validation of biomarkers.
Ex vivo blood stimulation
Ex vivoEx vivo
Ex vivo means that which takes place outside an organism. In science, ex vivo refers to experimentation or measurements done in or on tissue in an artificial environment outside the organism with the minimum alteration of natural conditions...
blood stimulation is a process by which researchers can analyse the immunological biomarkers of drug-effect in healthy volunteers. Blood samples taken from normal 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. Most research using this method is carried out by Phase I clinical research organisations, allowing them to collect blood samples and analyse them instantly without degradation of the samples.
See also
- Biomarker
- Biomarker (medicine)Biomarker (medicine)In medicine, a biomarker is a term often used to refer to a protein measured in blood whose concentration reflects the severity or presence of some disease state...
- Clinical chemistry
- Clinical proteomicsClinical ProteomicsClinical Proteomics is a peer-reviewed medical journal published quarterly by Humana Press. covers scientific research in the field of translational proteomics with an emphasis on the application of proteomic technology to all aspects of clinical research. It was established in March 2004 and the...
- Drug discoveryDrug discoveryIn the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which drugs are discovered or designed.In the past most drugs have been discovered either by identifying the active ingredient from traditional remedies or by serendipitous discovery...
- GenomicsGenomicsGenomics is a discipline in genetics concerning the study of the genomes of organisms. The field includes intensive efforts to determine the entire DNA sequence of organisms and fine-scale genetic mapping efforts. The field also includes studies of intragenomic phenomena such as heterosis,...
- ProteomicsProteomicsProteomics is the large-scale study of proteins, particularly their structures and functions. Proteins are vital parts of living organisms, as they are the main components of the physiological metabolic pathways of cells. The term "proteomics" was first coined in 1997 to make an analogy with...
- SecretomicsSecretomicsSecretomics is a subset of proteomics in which all of the secreted proteins of a cell, tissue, or organism are analyzed. Secreted proteins are involved in a variety of physiological processes, including cell signaling and matrix remodeling, but are also integral to invasion and metastasis of...