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On this episode of Translating Proteomics, hosts Parag Mallick and Andreas Huhmer of Nautilus Biotechnology discuss the challenges and opportunities of plasma proteomics. Their conversation focuses on:

·      Why blood plasma may be a good source of protein biomarkers

·      Current methodologies and pitfalls in plasma proteomics

·      The path forward for plasma proteomics

What is Plasma Proteomics?

For those who are new to this topic, plasma is the liquid portion of the blood distinct from fractions containing red and white blood cells. Given the relatively non-invasive ways physicians can collect patient plasma, and the blood’s intimate association with tissues throughout the body, plasma is potentially an excellent source of protein biomarkers. Yet, it is quite difficult to measure the levels of all plasma proteins because their concentrations span over 12 orders of magnitude. This episode features an in-depth discussion of the ways plasma proteomics efforts have and have not lived up to the promise of biomarker discovery and what we can do to advance plasma biomarker discovery efforts in the future.

Chapters

00:00 – 01:01 – Intro

01:02 – 4:55 – What is the promise of plasma proteomics?

04:55   – 07:23 – Is the plasma proteome really the best source of biomarkers?

07:23 – 10:16 – How do proteins get into the blood and what are the implications for biomarker discovery?

10:16 – 13:59 – Is it clear that proteins are the best candidates for blood biomarkers?

13:59 – 19:57 – Advances in and the future of comprehensive plasma proteomics

19:57 – 22:31 – Pros and cons of fractionating the plasma proteome to discover biomarkers

22:31 – 28:14 – Progress in identifying multiomic plasma biomarkers and the path forward

28:14 – End – Outro

Resources

Nano-omics: nanotechnology-based multidimensional harvesting of the blood-circulating cancerome (Gardner et al. 2022)

o   Review from focused on the development multiomics liquid biopsies

Multicompartment modeling of protein shedding kinetics during vascularized tumor growth (Machiraju et al. 2020)

o   Work from Parag’s Lab investigating tumor protein shedding

Simulation of the Protein-Shedding Kinetics of a Fully Vascularized Tumor (Frieboes et al. 2015)

o   Tumor protein shedding work from Parag’s Lab

Mathematical model identifies blood biomarker-based early cancer detection strategies and limitations (Hori and Gambhir et al. 2011)

o   Study modeling how much protein could be shed and detected from different size tumors

The human plasma proteome: history, character, and diagnostic prospects (Anderson and Anderson 2002)

o   Review discussing the clinical importance of the plasma proteome and the wide range of protein abundance in the plasma proteome

Blood Biomarkers to Detect Alzheimer Disease in Primary Care and Secondary Care (Palmqvist et al. 2024)

o   An example of the potential power of blood plasma as a source of biomarkers

Plasma Proteome Project