Common questions in molecular biology: What is an example of a biomarker?

It’s time for your yearly wellness visit with your doctor. It’s the same thing every year. They check your weight, blood pressure, oxygen saturation and pulse. Perhaps you have to give a urine sample or have some blood drawn.

Each of these assessments represents a biomarker and tells the doctor something about your health. Biomarkers aren’t limited to bodily observations though; they can include an assessment of number or types of cells in your body (for example, through a complete blood count or histological examination), measurement of hormones in your blood (for example, a check of thyroid functioning by looking at levels of thyroid stimulating hormone), or presence or absence of certain genetic markers.

In this Common questions in molecular biology blog post, I explore what a biomarker is, give examples of different kinds of biomarkers and how they are used clinically, and discovery of new biomarkers through single-cell sequencing.

What are biomarkers?

Although the term biomarker sounds very sophisticated, checking biomarkers is a common activity at any routine medical appointment. At the most basic level, a biological marker or biomarker is an objective, reproducible, and quantifiable biological signature that is associated with a particular health outcome. For example, checking your blood pressure is an objective and quantifiable assessment that can be tracked between visits. Blood pressure is also a reliable indicator of health and risk for a variety of diseases, such as heart disease, stroke, or kidney problems. Biomarkers are commonly used in research studies to determine the efficacy of a new treatment modality. For example, does treatment with a new drug lead to lowered blood pressure six months later?

What are different types of biomarkers?

There are many different kinds of biomarkers. These can be divided up into the level of examination (e.g., whole body, organ, cell, subcellular level) or by their uses. For instance there can be diagnostic biomarkers, which are used to confirm the presence of disease. These will be important in future research in cancer as the field moves towards molecular diagnosis and away from organ-based diagnosis.

Monitoring biomarkers are used for tracking a medical condition, disease status, or response to treatment. This is similar to a response biomarker, where one observes a patient’s response to an intervention. For example, this could include regular monitoring of blood pressure in a patient taking blood pressure medication, or monitoring cholesterol levels in a patient taking cholesterol medication.

Predictive biomarkers are used to design treatments. For example, one can look at a patient’s genotype for the Serotonin Transporter (SERT) gene and see if they are or are not a good candidate for Selective Serotonin Reuptake Inhibitor (SSRI) medications. For example, if someone is homozygous for a common SERT mutation that results in a defective protein product, one would predict a poor response to SSRIs.

This is related to, but slightly different from a prognostic biomarker. A prognostic biomarker is used if someone already has a disease, and what is the likely outcome for the person. For example, a prognostic biomarker could be used to determine the likelihood that a disease will get worse. This is not the same as a susceptibility or risk biomarker. These biomarkers are used to assess how likely it is for someone without a disease to develop the disease. For example, having gene mutations associated with developing cancer such as the BReast CAncer (BRCA) genes. People with BRCA mutations are more likely to get breast cancer over the course of their lives.

The final general class of biomarkers is safety biomarkers. These can be used to monitor response to a medical treatment and if its side effects may justify discontinuing the treatment. These could also be used to monitor the impacts of exposure to some kind of environmental toxin.

How do scientists find biomarkers?

Although some biomarkers such as checking blood pressure or measuring amounts of various compounds in the blood will continue to be clinically useful, molecular biomarkers, such as differences in gene expression among different cell types are increasingly valuable.

The most exciting development in biomarker discovery is the use of spatially resolved single-cell sequencing using technologies like NanoString’s CosMx Spatial Molecular Imager. Although many molecular biomarkers were identified using next-generation based technologies like single cell RNA seq, single-cell sequencing has the advantage of providing not only genomic information, but also multinomic information in a spatial context. Preservation of spatial information is critically important for fully understanding the function of individual cells within their tissue specific context.

Single-cell sequencing is revealing novel molecular biomarkers

Biomarkers are any kind of reliably quantifiable and objective biological measure that provides insights into one’s health status. Classification of biomarkers can be done at either the level of biomarker (e.g., full body versus molecular level) or by its usage (e.g., monitoring, predictive, or prognostic biomarkers). Identification of new molecular biomarkers is an exciting area of research in biology.

New technologies such as single cell sequencing using NanoString’s CosMx Spatial Molecular Imager are useful for biomarker discovery that account for both genomic and spatial information. It will be exciting to see how these novel biomarkers play into the future of routine medical care.

The CosMx™ SMI and decoder probes are not offered and/or delivered to the Federal Republic of Germany for use in the Federal Republic of Germany for the detection of cellular RNA, messenger RNA, microRNA, ribosomal RNA and any combinations thereof in a method used in fluorescence in situ hybridization for detecting a plurality of analytes in a sample without the consent of the President and Fellows of Harvard College (Harvard Corporation) as owner of the German part of EP 2 794 928 B1. The use for the detection of cellular RNA, messenger RNA, microRNA, ribosomal RNA and any combinations thereof is prohibited without the consent of the President and Fellows of Harvard College (Harvard Corporation).