Biomarkers: Definitions, Types, and Applications

Infections caused by pathogens such as bacteria, viruses, fungi, and parasites are the major threats worldwide. Fortunately, such infections are detectable. Detecting diseases in early-stage reduces mortality and morbidity to a great extent. The early detection is based on a biological marker (biomarker). The marker captures what is happening in a cell or an organism at a given moment. Biomarkers are biological signals present in blood, other body fluids, and tissues that indicate a normal or abnormal process, condition, or disease.

Definitions and Concepts of Biomarkers

WHO has defined a biomarker as “almost any measurement reflecting an interaction between a biological system and a potential hazard, which may be chemical, physical, or biological. The measured response may be functional and physiological, biochemical at the cellular level, or molecular interaction.”  

A biomarker is a defining trait in an organism that responds to a toxicant disturbance of the normal functioning of an organism. It can be measured accurately and is reproducible, providing the data.

The biomarker is an indicator or a medical sign indicating the body’s biological process, pathogenic process, or response to exposure or intervention, including therapeutic interventions. Such signal from the body helps doctors understand the impact of the diseased condition in the body. Normal physiology and its disturbance by contaminants are necessary for adequately interpreting a signal given by a biomarker.

Furthermore, the biomarker can evaluate the potential risk to the population, communities, or ecosystem. The biomarker is an early warning signal to humans or the environment before irreversible damage.

The biomarkers are the signs of disease, not the symptoms.

Medical signs do not correlate with medical symptoms or patients’ sense of well-being. The biomarker is measurable but does not define how a person feels or functions. The biomarker can be undetectable and remain without effects on health. The term biomarker is new, but signs have been practiced to detect disease for centuries.

The Key Terms Involved 

Some essential terminologies frequently used while studying the biomarkers are:

Clinical endpoint

It is a variable that reflects or characterizes how a subject feels, functions, or survives. It represents a study subject’s health and wellbeing from the subject’s perspective.

Surrogate endpoint

Surrogate endpoints are a small subset of well-characterized biomarkers with well-evaluated clinical relevance. The surrogate endpoint is used as a substitute for a direct measure of how a patient feels, functions, or survives. For example, an increase in cholesterol level during a heart attack can be a surrogate endpoint, whereas chest pain is a clinical endpoint. All surrogate endpoints are biomarkers. However, all biomarkers are not helpful surrogate endpoints.


Validation is an evaluation or qualification method for ensuring the accuracy of biomarker data.

Characteristics of an Ideal Biomarker

Biomarker have specific characteristics which make them appropriate for checking a particular disease condition.

An ideal biomarker should be

  • Easily measured
  • Fast and Safely measured
  • Cost-efficient to follow up
  • Modifiable with treatment
  • Consistent across gender and ethnic groups
  • Specific to the toxicant type showing a concentration-response (dose-response) relationship.

Types of Biomarkers

Many biomarkers are useful today to detect infectious, non-infectious, and metabolic diseases.

Biomarker include a wide range from simple metabolic studies, like blood pressure, heart rate, X-rays, and blood and urine analysis, to complex histologic and genetic tests of blood and other tissues.

Similarly, biomarkers are mainly biomolecules categorized as carbohydrates, proteins, hormones, enzymes, lipids, nutrients, DNA/ RNA, and many more.

Biomarker is classified based on their role in the body as biomarker of exposure, biomarker of effect, and biomarker of susceptibility.

Biomarker of exposure

It detects whether the organism has been exposed to a particular chemical or medium. A biomarker of exposure is an exogenous substance or its metabolites or product. An example of a biomarker of exposure is the blood lead concentration which is the mark of exposure to lead. 

Biomarker of effect

Biomarker of effect is a measurable physiological, biochemical, or other change within an organism on exposure to an exogenous substance. The alteration in pulmonary function tests in children after exposure to environmental tobacco smoke is the biomarker of effect.

Biomarker of susceptibility

It is an inherent or acquired ability of an organism to respond to exposure to a specific substance. If the organism is resistant, the exposure will remain undetected.

Other biomarkers indicate molecular, histologic, radiographic, and physiologic characteristics and prognosis.

Prognostic biomarker likelihood of a clinical event, recurrent or progression, disease-related end-point event, or a worsening in clinical trials. E.g. Total kidney volume in autosomal dominant polycystic kidney disease.

Biomarkers can also be classified according to the site of infection, for example, hematological biomarker, neurotoxicity biomarker, immunotoxicity biomarker, reproductive and development toxicity biomarker, etc.

Some examples of biomarkers are in the figure.

Different types of Biomarkers
 a) Host response on infection b) Host biomarkers of infection c) Biomarkers of bacterial and viral infection
Image source: (Qureshi & Niazi, 2020)       

Applications of Biomarkers

Promising biomarkers shorten the diagnosis and treatment or clinical trial period. Mainly, biomarkers are applicable in: clinical diagnosis, treatment, hazard identification, research, etc.

Clinical Diagnosis

Biomarkers are useful alone or in combination to measure the presence or progress of the disease like cancers. Every system has its specific biomarkers. Most are easy to measure and form part of a routine examination.


We can enhance medical product development by speaking the same “biomarker language” to get appropriate treatments for patients. Biomarker help measure the efficacy of drugs.

Hazard Identification and Safety 

Biomarker can measure the safety or toxicity of therapeutic substances or particular environmental exposure.


It plays a critical role in biomedical research. Various research has been conducted to learn the interaction between biomarkers and treatment effects. Studies are being conducted to discover new biomarkers that are more sensitive and specific.

Screening and monitoring

Biomarker is measured for screening the disease of an individual or a population in a rapid way. Biomarkers are also applicable to assess the status of the disease regularly.


Biomarker indicate an increased or decreased likelihood of disease occurrence or progression. The biomarker helps to reduce the disease occurrence or any adverse effects of the disease.

Selection and Validation of Biomarkers

Validation is critical for ensuring that the biomarker data are accurate and reproducible. Analytical and clinical validation is used to test devices and working efficiency. Analytical validation confirms that tests and tools are acceptable in terms of specificity, accuracy, precision, and other characteristics of biomarkers. It is evaluated during specimen collection, handling, and storage procedures.

Clinical validation ensures that tests or devices perform as planned and acceptably identify, measure, or predict the concept of interest. Once qualified for a particular context of use, a biomarker will be available to the public. Context of use is a statement that clearly describes how biomarkers are used for drug development-related purposes in detail.

Biomarkers Testing

Biomarkers can be anything from abnormal cells to mutations in DNA. So, biomarker testing is done in the following ways:

  • A liquid biopsy is performed to detect cancer biomarkers in tumor cells.
  • Cytogenetic and Karyotyping tests study chromosomes’ structure, functions, and abnormalities.
  • Different laboratory tests analyze proteins or any chemical substances as a sign of disease. 
  • Immunohistochemistry also helps detect antibodies specific to the antigens (biomarkers) using various immunological methods like precipitation, agglutination etc.
  • Different methods of sequencing DNA are performed to identify mutations in the DNA. Sanger sequencing and whole-genome sequencing (WGS) are some of the ways of DNA sequencing.


Understanding the relationship between biomarkers and clinical outcomes is integral to drug development. Measuring validated biomarkers can improve observational studies’ quality and reliability, enhancing the treatment.

Specific and sensitive biomarkers have been important challenges. Advances in molecular biology led to the inventions of new biomarkers which are more accurate and provide early diagnosis and personalized treatment. Similarly, it is necessary to evaluate and reevaluate the validity of biomarkers for their proper use.


Srijana Khanal

Hello, I am Srijana Khanal. Former faculty teacher in Microbiology Department at National College, NIST. Involved in the field of teaching for almost 10 years. I am very passionate about writing (academic as well as creative). My areas of interest are basic science, immunology, genetics, and research methodology.

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