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A Novel Method For Discovery of Peripheral Blood Biomarkers in Idiopathic Pulmonary Fibrosis Using Extensive Depletion and TMTcalibratorTM Tissue-Enhanced Plasma Proteomics
EP29497
A Novel Method For Discovery of Peripheral Blood Biomarkers in Idiopathic Pulmonary Fibrosis Using Extensive Depletion and TMTcalibratorTM Tissue-Enhanced Plasma Proteomics
Submitted on 13 Dec 2018

I. Pike1, M. Bremang1, P.J. Wolters 2, R. Gaster3, S. Turner3, M. Decaris3
1 – Proteome Sciences plc, Hamilton House, Mabledon Place, London, WC1H 9BB, UK; 2 – University of California at San Francisco, San Francisco, USA; 3 – PLIANT Therapeutics, 700 Saginaw Drive, Suite 150, Redwood City, CA 94063, USA
This poster was presented at ATS 2018
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Poster Abstract
A modern mass spectrometric (MS) project detects all major protein (and post translational modification) changes between samples. We aim to correlate changes observed in the gut microbiome to detectable proteomic changes and quantify how these changes relate to disease via finding a protein based biomarker(s) ideally in the periphery. These identified protein biomarkers can then be used in on-going research via ELISA or, if not available, targeted MS.

We can work in most matrices, but blood is the most common.
MS typically reports a few hundred proteins per sample in plasma.
By using a tissue trigger in an multiplex single MS experiment, we can increase this protein pool to around 4,000 proteins. This approach is known as TMTcalibrator™.
If we remove the top 65 higher concentration proteins in plasma via Super Depletion, the proteins detected rises to 8,500+.

As expected, many proteins/ptm’s might well be common in all the samples used, but with larger protein numbers and extensive bioinformatics, we increase the likelihood to quantify unique proteins that are representative of the class comparison(s) within the experiment. Proteins identified in the Discovery Services above can then be precisely quantified in our Targeted Services under CGLP as single or multiplex protein measurements if no other method (like ELISA) is available.

Peripheral biomarkers related to the pathogenesis of idiopathic pulmonary fibrosis (IPF) are urgently needed to improve diagnosis, selection and assessment of treatment, particularly in the context of new drug development. Recent improvements in the depletion of high and medium abundant proteins and development of tissue-enhanced fluid proteomics have increased the breadth and depth of plasma proteome coverage. We have now combined these methods to obtain unparalleled coverage of the IPF plasma proteome.Report abuse »
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