Translating Proteomics Episode 11 – Plasma Proteomics – The Dream and the Nightmare

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 in 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)
  Review from focused on the development multiomics liquid biopsies
• Multicompartment modeling of protein shedding kinetics during vascularized tumor growth (Machiraju et al. 2020)
  Work from Parag’s Lab looking at tumor protein shedding
• Simulation of the Protein-Shedding Kinetics of a Fully Vascularized Tumor (Frieboes et al. 2015)
  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)
  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)
  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)
  An example of the potential power of blood plasma as a source of biomarkers

All Translating Proteomics episode links

Ep 1 – Poised for a Proteomics Breakthrough
Ep 2 – Putting Proteomics to Work
Ep 3 – Biology in Space and Time
Ep 4 – Single-protein Biomarkers Don’t Cut It
Ep 5 – Why the Dogma around Biology’s Central Dogma Is Wrong
Ep 6 – The Future of AI in Biomedicine
Ep 7 – Harnessing Proteoforms to Understand Life’s Complexity
Ep 8 – Expanding the Druggable Universe with Proteomics
Ep 9 – Are proteins a myth? With Special Guest Neil Kelleher
Ep 10 – Protein Function 201 with Kathryn Lilley
Ep 11 – Plasma Proteomics – The Dream and the Nightmare
Ep 12 – A New Era in Alzheimer’s Research with Sarah DeVos
Ep 13 – AI and Biotech – The Promise and the Pitfalls with Vijay Pande and Matt McIlwain