TrueDiscovery Archives - Biognosys

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide. Although immunotherapy has improved the treatment of NSCLC, a significant number of patients still fail to respond or develop resistance.

Plasma is the most widely collected biofluid and an invaluable source of biomarkers. The analysis of plasma using discovery mass spectrometry–based proteomics faces challenges as the 22 most abundant proteins constitute more than 99% of the total protein content. This is hindering the detection of lower abundant proteins, potentially disease-relevant biomarkers. To overcome this, we developed and optimized an enrichment workflow, termed P2 Plasma Enrichment System, based on protein corona formation. Protein corona formation leads to a reduction in dynamic range enabling the detection of lower abundant proteins. We characterized P2 in terms of robustness quantitative precision and quantitative accuracy with acquisition throughputs ranging from 40 to 500 samples per day.

Plasma is the most widely collected biofluid and an invaluable source of biomarkers. The analysis of plasma using discovery mass spectrometry–based proteomics faces challenges as the 22 most abundant proteins constitute more than 99% of the total protein content. This is hindering the detection of lower abundant proteins, potentially disease-relevant biomarkers. To overcome this, we developed and optimized an enrichment workflow, termed P2 Plasma Enrichment System, based on protein corona formation. Protein corona formation leads to a reduction in dynamic range enabling the detection of lower abundant proteins.
We characterized P2 in terms of pre-analytical variation, robustness and quantification. Finally, we applied it to find predictive biomarkers in a multicentric phase II clinical trial (SAKK17/18) in patients with non-small cell lung cancer (NSCLC).

Bruderer R, Muntel J, Müller S, Bernhardt OM, Gandhi T, Cominetti O, Macron C, Carayol J, Rinner O, Astrup A, Saris WHM, Hager J, Valsesia A, Dayon L, and Reiter L. Molecular & Cellular Proteomics.

We have established a robust capillary-flow DIA platform capable of measuring a large number of clinical samples in a fast and reproducible manner. The platform allowed the acquisition of 31 plasma proteomes per day, and a total of 1508 samples from the dietary intervention study DiOGenes measured on a single column. Our workflow revealed distinct biological reactions to weight loss and maintenance, and the comparison to independent studies showed the robustness for potential biomarker discovery.

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In January, we announced our new strategic partnership with Bruker to broaden access to our leading proteomics services & tools for biopharma and #biomarker customers.

In this exciting SpotLight episode, Biognosys’ CEO Oliver Rinner and Rohan Thakur, President of the Bruker Life-Science Mass Spectrometry division, discuss the many synergies of the new alliance and give an outlook of what the future might hold.

 

In NSCLC, the identification of circulating predictive biomarkers is critical to improve patient stratification. Circulating biomarkers have the advantage of accessibility of samples but challenges arise in detecting disease-relevant biomarkers in plasma, where low-abundance circulating analytes are often obscured by highly abundant proteins. This underlines the need for highly sensitive, reproducible assays to detect subtle changes. Therefore, developing a sensitive, reproducible method for biomarker discovery in plasma could significantly enhance clinical outcomes for patients with NSCLC.

To address this need, we developed a novel workflow combining particle enrichment (P2) and quantitative mass spectrometry (DIA-MS). We deployed this method on plasma samples from a multicentric phase II clinical trial (SAKK17/18) in patients with NSCLC (Fig. 1). Longitudinal plasma samples were collected at baseline (n=33) and at two post-dose time points (C1D8, n=31 and C2D1, n=31). The samples were subjected to the developed P2 workflow and unbiased mass spectrometry analysis (Fig. 2), leading to the quantification of 9283 proteins across all 95 samples. With this depth at plasma proteome profiling, we could cover up to 12 orders of magnitude, detecting low-abundance tissue/cell proteins from leakage events as well as proteins from extracellular vesicles.

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