RE: Plasma analysis tmt calibrator28 Jul 2021 09:57
In 2019, the company and collaborators at the Centre for Neuroscience and Trauma at London's Blizard Institute published a study in Nature Scientific Reports that used TMTcalibrator to analyze plasma samples from 29 subjects with ALS. Using brain tissue from deceased ALS patients as the carrier sample, the researchers quantified 1,126 proteins in all samples.
Andrea Malaspina, formerly professor of neurology at the Blizard Institute and now a professor at University College London and senior author on the Nature Scientific Reports study, said the approach provided a much deeper look into the plasma samples than he was accustomed to from past work.
"My experience with large-scale analysis of proteins in a matrix like plasma was that you just pull out the most abundant proteins that make up 95 percent of proteins in blood," he said. "With the TMTcalibrator we were able to pull out signal from the low-abundance proteins derived from brain, including neurofilament isoforms and other proteins that are of interest in the ALS space."
Malaspina added that the quantitative nature of the data provided insight into "differential regulation between samples."
As an example of the approach's power, Pike cited work on idiopathic pulmonary fibrosis the company did in collaboration with researchers at the University of California, San Francisco and Pliant Therapeutics and presented at the American Thoracic Society annual meeting in 2018. Using the approach, they quantified roughly 5,600 proteins in all 30 plasma samples they analyzed.
That depth of coverage compares favorably with most any other approach to plasma proteome analysis. In March, for instance, Swiss proteomics firm Biognosys said that it expects by the end of the year to begin offering a new discovery proteomics workflow that will allow it to quantify around 2,700 proteins in a typical plasma study, and that it expects to manage around 3,300 proteins in large-scale discovery studies by the end of 2022.
Also in March, Qing Wang, CEO of Baltimore-based multi-omics company Complete Omics, said that the firm plans by the end of the year to launch a targeted mass spec assay that will quantify 4,550 proteins in plasma.
In an analysis last year of 141 plasma samples, proteomics firm Seer showed its Proteograph system could identify roughly 2,000 proteins.
SomaLogic's aptamer-based SomaScan platform can measure 7,000 proteins in plasma, while Olink is able to measure 1,500 proteins in plasma and expects to expand that figure to around 3,000 in coming years.
The downside of TMTcalibrator compared to many of these other workflows is its reliance on extensive depletion and fractionation. The depletion approach used can process only around 15 samples a day, while the depth of coverage reached in the pulmonary fibrosis study required splitting samples into 30 different fractions, each run on a two-hour liquid chromatography gradient. This limits the method's throughput, at a time when the proteomics fi