The proteome is to proteins what the genome is to genes. It’s the collection of all the proteins inside a cell, organism, or biological sample, as well as the ways those proteins interact with each other. Because proteins are so fundamental to life, studying the proteome means studying the inner workings of life itself.
For years, scientists have been asking the question, “What makes a living cell tick?” If you peer inside a cell, you’ll find lipids, carbohydrates, nucleic acids, and proteins – the four macromolecules that form the building blocks of life. All four of these combine to form the various structures in cells, from their outermost membranes to their innermost machinery. But when it comes to the mechanisms that make cells function, it’s proteins that are getting work done.
The proteins in a cell are dictated by its genome. This DNA contains the blueprints for life in the form of the genetic code. Inside a cell, DNA is transcribed into RNA, which is in turn translated into proteins. This process moving from DNA to RNA to protein is so foundational to all life that it’s referred to as the central dogma of biology.
Ever since the Human Genome Project completed its first sequence 20 years ago, advances from genetic and genomic research have made it easier to learn about every component of the central dogma, including proteins. But truly effective tools for studying all the proteins in the last component of that dogma, the proteome, are still lacking. While we can comprehensively sequence DNA and RNA, scientists are still unable to see the full scope of the proteome.
The proteome is all the proteins in a biological sample. A researcher might want to understand the proteome of a single cell, a tissue sample, an individual organism, or an entire species. So, how is the proteome defined? The exact definition of the proteome – and the size of it – depends on the scale of your investigation.
Nonetheless, proteomes are generally huge and complex, making them quite a challenge to study. A single cell can contain billions of proteins, some of which are entirely different from each other, while others are variations on the same gene product (called proteoforms). But understanding the proteome is worth it: By studying the proteome of a cell, you can learn not only which proteins you have and in what amounts, but also dig into how the cell works.
The ability to comprehensively analyze the proteome at scale is improving quickly. One older method for analyzing a proteome was protein by protein, using protein sequencing techniques. Protein sequencing and other traditional protein analyses, like those using small numbers of antibodies and other affinity reagents, allow the investigator to look at a handful of targeted proteins at once. More recently, proteome profiling efforts make use of technologies like mass spectroscopy that increase throughput significantly, though most modern proteomic analyses still only profile 8–35% of the proteins in a given sample.
With increasing interest in proteomics, we may soon see the completion of a Human Proteome Project that rivals the Human Genome Project. This is an extraordinary undertaking being organized by the Human Proteome Organization (HUPO). The goal of this international effort is to reveal the function of every protein. As of March 2022, they have reported finding 18,407 proteins, and estimate they have 6.8% of the human proteome to go.
Characterizing each human protein in this way will supply an important framework for proteome research but is just the first step to understanding the human proteome — like having an encyclopedia entry about an animal in-hand before setting out to study its ecology. To build upon this baseline knowledge of the proteome, researchers will need new technologies that allow them to understand how the proteome varies between cells and organisms, health and disease/stress, in response to drug treatments, and much more.
Unlocking the proteome will be as fundamental to biology as understanding DNA and RNA. This means proteomics applications will span all sectors that deal with cells and life in general. By looking across genomics (DNA), transcriptomics (RNA), and proteomics (proteins) all together, the burgeoning field of multiomics is bringing with it an unparalleled depth of biological understanding.
One of the most valuable pieces proteins add to the –omics space is mechanism of action. For instance, the chain of mechanisms that turn a gene into a protein are complex, relying on interactions between the genome, other parts of the cell, and the environment. Adding insights from proteomics to genomics connects the dots between environment, DNA, RNA, proteins, and biological function. Even if DNA encodes the architecture for these interactions, the proteins are the last step in this chain and the most closely linked to how cells, tissues, and organisms behave. This means manipulating proteins can have direct impacts on processes across all these levels of biology.
Some of the most immediate applications of adding proteomics to the study of multiomics will be in health. Measuring the proteins in both healthy and diseased cells will increase our understanding of disease mechanisms and provide protein biomarkers for diagnosis as well as targets for treatment. Importantly, proteins are generally easier to target with drugs than DNA or RNA, so knowing what proteins are directly involved in a disease provides researchers with clear paths to therapeutic development.
For example, an understanding of the proteome of cancer cells will allow for the development of precision medicines that target the mechanisms enabling tumor growth. In addition, some think diseases like Alzheimer’s are caused by a buildup of proteins. Thus, proteomics studies could identify biomarker proteins that are indicative of the early stages of this build up and that could be targeted to either prevent or reverse this process. This may lead to novel treatments for Alzheimer’s and other neurological conditions.
Additional applications of proteomics include:
We are excited to be at the forefront of efforts to unleash the proteome and bring applications like those described above to the researchers, doctors, and patients who need them. To learn more about how Nautilus is driving a revolution in proteomics analysis, subscribe to the Nautilus blog and never miss an update on the upcoming #ProteomicsRevolution.
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