Proteomics studies typically look at vast numbers of proteins in a sample to see which proteins are present, and how many of each there are. This kind of broadscale protein analysis is good for understanding what proteins are in a sample, but in some cases, researchers want to conduct in-depth analyses of certain proteins or groups of proteins. This kind of targeted protein analysis, also known as targeted proteomics, can show scientists how individual proteins have been modified to create a variety of variants known as proteoforms.
Proteoforms can change how cells and tissues work in important ways. They may, for instance, help forestall a tumor’s growth or help the body respond to infection. Understanding which proteoforms are present, and in what number, can show scientists what’s happening inside cells with unprecedented resolution.
What is targeted proteomics?
There are only about 20,000 protein-coding genes in the human body, but most of these proteins are understudied and there are many ways they can be modified during their production. As a result, the human proteome contains an estimated 6 million proteoforms, most of which we know very little about.
The presence or absence of particular proteoforms can have important effects on the body. One process that leads to different proteoforms, called post-translational modification, helps regulate communication between cells, control cell growth, and more. Mistakes in protein modifications are also at the root of many human diseases. For instance, mutations that disrupt post-translational modifications are thought to cause a type of cancer called diffuse intrinsic pontine glioma.
We’ve yet to study all — or even most — proteoforms and there is much left to discover in the human proteome. Targeted protein analysis studies are one way to reveal more of the proteome.
The Nautilus Proteome Analysis Platform is designed to enable targeted protein analyses that look for specific proteoforms among potentially millions present in a sample. The platform is also designed to conduct broadscale analysis of nearly the entire proteome and it is expected that these two analysis modalities will complement one another to enable novel biological insights.
Uses for targeted proteomics
Targeted proteomics can uncover which proteoforms are present, and how many of them there are. That could be useful for studying any number of conditions known to be linked to changes in protein type and abundance, or even discovering the roots of new biological functions.
One prominent way proteoforms impact biology is by changing which genes our cells express. Inside chromosomes, specific proteins called histones act as spools that DNA winds around. Changing a histone’s structure can affect which genes are transcribed into mRNA. For example, some kinds of post-translational modifications cause the spooled DNA to coil up tightly, making the genes in it unavailable for transcription, while others cause it to unwind, allowing transcription to happen.
This process of controlling gene transcription plays a big role in how our bodies work — or don’t. For example, a recent review in the journal Frontiers in Genetics highlights how histone modifications affect the aging process, and notes that diet impacts which histone modifications occur in our bodies. Studying these modifications in more detail could reveal which specific histone modifications are linked to negative outcomes as we age, potentially revealing ways to slow down the aging process.
Targeted protein analysis with the Nautilus Proteome Analysis Platform
Next-generation proteomics technologies like the Nautilus Proteome Analysis Platform are designed to analyze samples comprehensively and at the single-molecule level. This may enable researchers to see all the ways a given protein has been modified, something that is rarely possible with traditional technologies like mass spectrometry. In addition, single-molecule measurements are expected to make it much easier to see the extent to which a given protein has been modified. Finally, with the ability to conduct proteoform analysis quickly, researchers will be able to compare proteoforms across samples, allowing them to link changes to proteoforms with real-world outcomes.
The Nautilus Proteome Analysis Platform is designed to not only enable more powerful targeted protein analysis, but also to democratize these analyses and make them more accessible to researchers in many different fields. With an integrated workflow and accelerated analysis, more labs will be able to conduct targeted protein analysis, potentially opening the door to a wide variety of novel insights into basic biology, drug target discovery, and diagnostic development.
Proteomics applications in medicine, basic biology, and beyond
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