How targeted proteomics and targeted protein analyses are changing biology

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. Each proteoform is defined by the full set of modifications it has, whether those modifications come from alternative splicing, post-translational modification, or any other source. Thus identifying proteoforms requires single-molecule analysis of full-length proteins.

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.

Watch this animation to learn how we measure proteoforms on the Nautilus^TM Proteome Analysis Platform

What is targeted protein analysis? 

Targeted protein analysis studies enable researchers to learn more about specific proteins and proteoforms present in a sample and begin to see what their roles might be. They can include functional proteomics studies assessing how proteins function through interaction proteomics experiments that assess how proteins work together. Targeted protein analyses can also count the number of different kinds of proteoforms present, which can point researchers to specific functions for these proteoforms in particular cell types or other biological contexts.

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^TM Proteome Analysis Platform 

Next-generation proteomics technologies like the Nautilus Proteome Analysis Platform are designed to analyze proteins at the single-molecule level. This may enable researchers to see all the ways a given molecule of a single type of protein has been modified (i.e. enable them to identify proteoforms), something that is rarely possible with traditional technologies like mass spectrometry. 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.