Amazing work from Daniel, Fritz and team!

Paper: www.science.org/doi/10.1126/...
Variant effect map review: www.nature.com/articles/s41...
Cardiovar consortium: www.genomeweb.com/research-fun...
Atlas of variant effect maps: www.mavedb.org

These sorts of maps will increasingly become central tools in our quest to understand disease-causing human genes to help patients and prevent disease.

Further, functional scores correlated with hyperlipidemia phenotypes in prospective human cohorts and augmented polygenic scores to improve risk inference.

This yielded sequence–function maps that recapitulate known biochemistry, offer functional insights, and provide evidence for interpreting clinical variants.

Here, Daniel and team tested the impact of nearly all possible (~17,000) missense coding variants in the receptor for LDL ("bad cholesterol"), the gene most commonly responsible for FH. Importantly, they tested two functional readouts: LDLR cell-surface abundance and LDL uptake.

The new science of "variant effect mapping" uses cellular biology to model all possible variants in important genes in advance, providing scientists and clinicians with estimates as to their pathogenicity.

Familial hypercholesterolemia (FH) is among the most common inherited cardiovascular diseases. It causes early heart attacks that are preventable with modern therapy. The challenge is that many variants identified by sequencing are of unclear significance.

Huge thanks to Geoffrey Ginsburg for the idea for the symposium and to fellow Glaswegian Stephen Kingsmore for co-chairing. At the following session, we enjoyed a lively discussion on the future of AI in healthcare.

Atul and his legacy will not soon be forgotten. ❤️

I will treasure the times I got to spend in the vicinity of his protons, neutrons & electrons.

The world is darker today for the loss of his light.

RIP

I loved his travel tips and his detailed knowledge of United lounges.
I loved how all his tweets started with “Wow!”
I loved how much he loved mentoring students and trainees.
I loved how proud he was of his wife and daughter.
I loved being able to call him a friend.

I loved his love of data, of gadgets and of new computers.
I loved how he would sit in the back of meetings and code.
I loved his stories.
His talks were legendary.
I loved how he was once paid enough to buy "a small car" for one of his talks.