EP 160: Artificial Intelligence, GWAS in Drug Discovery, and Career Insights with Dr. Eric Fauman, Executive Director and Head of Computational Biology in the Internal Medicine Research Unit at Pfizer

0:00 Introduction
1:30 The power of social media: How Eric published 10 papers based on ideas that he discussed on Twitter
5:50 Explanation of The Table of Everything, an internal database at Pfizer that catalogs nearly 20,000 human genes and their associated diseases and traits
13:20 How Eric’s team works to correlate genome-wide association study (GWAS) results to real biological phenotypes and outcomes
18:10 Introduction to protein quantitative trait locus (PQTL), including its importance in biological and genetic data
25:10 Examining the evolving bottlenecks in drug development and the challenges of validating genetic targets
28:30 Navigating the gap between genetic hits and biological understanding, and how AI or functional studies could bridge this in target discovery
32:20 Linus Pauling's mentorship of Eric and how he might react to AlphaFold2’s breakthroughs in structural biology
35:15 Eric's take on using AI and how he's experimenting with it on trusted datasets
41:00 An introduction to Mendelian randomization, as well as its strengths and limitations
47:00 How Eric uses the TOP Model (Talent, Opportunity, and Passion) to guide this career choices and path
52:00 Diversity and collaboration in genetics research and implementation
55:00 Closing remarks
Resources mentioned throughout the episode:Mendelian Randomization with Proxy BiomarkersPaper: Mendelian randomisation with proxy exposures: challenges and opportunities, I Rahu, R Tambets, EB Fauman, Kaur Alasoo (2024)Explores proxy biomarkers as a method to assess in vivo activity of a protein target.
Trait Colocalization and Causal GenesPaper: Integrative analysis of metabolite GWAS illuminates the molecular basis of pleiotropy and genetic correlation, CJ Smith, N Sinnott-Armstrong, A Cichońska, H Julkunen, EB Fauman, Jonathon Pritchard, Elife 11, e79348Demonstrates how traits with opposing effects on a genetic variant may suggest a causal gene sits between them
Metabolite Profiling in Human KnockoutsPaper: McGregor TL, Hunt KA, Yee E, et al. Characterising a healthy adult with a rare HAO1 knockout to support a therapeutic strategy for primary hyperoxaluria, Elife. 2020;9. Published 2020 Mar 24.
Community Workshop on Effector Gene StandardsPresentation: Watch on YouTube
TOP Model for Career GuidanceArticle: Grab the Helm: How to Take Charge of Your Purpose, Passion, Progress
The Table of EverythingOverview: Read more on Pfizer’s site
UK Biobank Protein QTL StudyPaper: Sun, B.B., Chiou, J., Traylor, M. et al. Plasma proteomic associations with genetics and health