Proteomics & DIA Mass Spectrometry in Neurodegenerative Disease Research

insights from industryNicholas DupuisDirector of Scientific Business DevelopmentBiognosys

Biognosys recently presented data from its updated DIA based proteomics workflows in CSF at Society for Neuroscience 2019 in Chicago, IL. News-Medical Life Sciences caught up with Nicholas Dupuis after the meeting to discuss what is new in proteomics and DIA mass spectrometry.

Why should proteomics be the chosen technology in multiplexed protein quantification studies?

Mass spectrometry-based multiplex proteomics is just one tool that can be applied for unbiased protein quantification in complex matrices such as plasma, urine, CSF, and tissue, which are rich in biological analytes. But it offers unique advantages which have become more apparent as the technology has continued to advance.

In particular, the mass spectrometry approach can make the best use of precious samples, now quantifying a large percentage of the expressed proteome (e.g., up to many thousands of proteins), with very modest sample requirements.

Additionally, peptide sequencing ensures its high specificity to avoid some of the well-known challenges with affinity-based capturing agents. In a properly designed experiment, the false discovery rate (FDR) is controllable at a standard 1%.

Lastly, and perhaps most importantly, the method is highly quantitative (relative or absolute), where the median CV across the thousands of proteins is typically well below 10%, which means that subtle changes to the global sample proteome are easily detected and quantified with high confidence.

Sergei Drozd / Shutterstock

How do DIA experiments provide an advantage over DDA studies?

DIA expands the capabilities of modern mass spectrometry instrumentation. This was recently demonstrated when we showed that DIA based acquisition enabled us to surpass the theoretical limit for DDA based acquisition in single-shot acquisitions. The result is that DIA ensures there are very few missing values in a data set, maximizing the number of proteins for biomarker analysis and improving the overall utility of an experiment.

These advantages feed directly into the scalability of the DIA approach, which ultimately enables an analysis of much larger sample sets on the order of 100s or even 1000s of samples.

By using DIA Mass Spectrometry, how are we able to develop and improve Alzheimer’s research?

AD is an extremely complex neurodegenerative disease where many factors, such as genetic predisposition (genome) and exposure to external stimuli (exposome), may play a vital role in the onset and development of the disease. These factors also result in a highly heterogeneous population of AD patients from different disease stages, which render their stratification extremely challenging based on single or a small panel of biomarkers.

We have recently updated our DIA-MS workflows, which enable the high-throughput and robust quantification of thousands of proteins across 10s to 100s of samples from only 100 µl of CSF. Our recent work, published at the Society for Neuroscience annual meeting, highlights the power of these workflows in a proof of concept study on AD patients.

We believe that this tool, which significantly increases the number of visible proteins in CSF, will enable more accurate phenotypic characterization of patients across many neurodegenerative diseases and support the development of the right drugs for the right patients.

What makes Biognosys and its products unique?

Biognosys’ focus over the past few years has been on the continued development of data-independent acquisition mass spectrometry (DIA-MS), and we strive to stay on the leading edge of protein quantification through multiple acquisition modalities. However, as the underlying methods and technology have matured, we have expanded our focus to improve the method robustness and throughput, intending to enhance the scale of sample analyses, while maintaining high protein numbers and precision.

This is made possible by the close collaboration between our R&D and contract research services departments, along with leading mass spectrometry vendors and academic groups in proteomics. As a result, when customers are looking to apply a proteomics approach in their research, they will be able to access leading-edge proteomics in a robust and scalable laboratory.

About Nicholas Dupuis

Dr. Nicholas Dupuis joined Biognosys in 2017 as a Director of Scientific Business Development.

Nicholas has over 15 years of experience in multiple forms of mass spectrometry and applications to the study of biological systems. Most recently, Nicholas has focused on implementing mass spectrometry technologies for diagnostic and translational biomarker studies.

At Biognosys he is particularly interested in applying unbiased proteomic methods to biomarker analysis in oncology, neuroscience, and immunology.  


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