There are lot's of cool new ways to measure the proteome!
High throughput proteomics could revolutionize our understanding of human disease, but it's going to take some major innovations to get us there!
Proteomics is the study of all of the proteins produced by an organism.
Proteins are:
Enzymes, structural components, signaling molecules, hormones, etc.
They basically do all of the work while DNA and RNA sit around and watch!
But proteins are also the ultimate end product of the information stored in our DNA and are created as a result of two processes:
Transcription - the conversion of DNA into the RNA message.
Translation - the conversion of that RNA message into functional protein.
For decades, DNA and RNA have stolen the show, mostly because innovations in nucleic acid sequencing have made decoding these messages a relatively simple process.
While we can glean some information about the biological status of an organism or tissue by sequencing DNA and RNA, we can actually measure functional biology by looking at the proteins!
And it's the proteins, or lack thereof that cause disease!
So why haven't we heard anything about proteomics?
In some respects, you have.
Many of the diagnostic tests that are administered when you see a physician are measuring protein concentrations or enzyme activity.
Unfortunately, the majority of these only look at a single protein at a time.
But, the real magic lies is in being able to measure all of the proteins!
And not just the select few that we've already found to be clinically relevant!
How can we measure thousands of proteins all at the same time?
We have options:
Mass Spectrometry - The go-to in this space has historically been matrix-assisted laser desorption/ionization (MALDI) and time-of-flight (TOF) mass analysis. This technique works by ionizing proteins, smashing them into a detector, and then imputing what was present before the ionizing and smashing.
Antibody/Aptamer Arrays - An old, low throughput, standby of protein detection has been the use of antibodies. However, innovations like those implemented by Olink which add a sequence tag to antibodies facilitates the multiplex counting of thousands of proteins at a time making this process much more high throughput with a wide dynamic range. A competing technology from Somalogic works similarly, however, they’ve created custom RNA aptamers to do the dirty work.
Protein Sequencing - This is done through a systematic decay and detection process. This involves the labeling of specific amino acids (Erisyon) and imputation of the peptide present based on where those labels appear or the use of fluorescent ‘recognizers’ (Quantum-Si) to detect the terminal amino acids throughout the decay process.