Doug Fowler

So excited to see you all in Melbourne next year!!!

Landscapes of missense variant impact for human superoxide dismutase 1 SOD1 variants cause the motor neuron disease amyotrophic lateral sclerosis. Axakova et al. functionally assay ∼86% of all possible SOD1 missense variants, producing a variant-effect map resource that ...

📣New today!
📄Landscapes of missense variant impact for human superoxide dismutase 1
🧑‍🤝‍🧑 @axakova.bsky.social @fritzroth.bsky.social & co

Multiplexed assays of variant effect for clinical variant interpretation - Nature Reviews Genetics Multiplexed assays of variant effect (MAVEs) are highly scalable experimental approaches used to generate functional data for genetic variants. In this Review, McEwen et al. discuss the advances in MA...

Interested in using MAVEs for variant classification?

Read our review by Abbye E. McEwen, Malvika Tejura, @shawnfayer.bsky.social, @leastarita.bsky.social & @dougfowler.bsky.social:
Multiplexed assays of variant effect for clinical variant interpretation
go.nature.com/3IdCfUb
rdcu.be/eFmll

📝Check out our review “Creating an atlas of variant effects to resolve variants of uncertain significance and guide cardiovascular medicine”, out in @natrevcardiol.nature.com. We review the use of Multiplexed Assays of Variant Effect and variant effect predictors in cardiovascular disease.

Functional evidence for G6PD variant classification from mutational scanning G6PD deficiency is the most common enzyme deficiency worldwide, and increases the likelihood of adverse reactions to certain drugs and foods. Identifying people at risk is challenging, since most are ...

It's been a long time coming but, my postdoc work characterizing thousands of variants in G6PD is now available! Many thanks to @maitreya.bsky.social @dougfowler.bsky.social @afrubin.bsky.social and their labs! www.biorxiv.org/content/10.1...

‪🗓️ Join us tomorrow! August 5
with @nurdankuru.bsky.social (CSHL) @cshlnews.bsky.social
and Ferdy van Geest (ErasmusMC)
#Genetics #RareDisease #MedicalGenetics
ℹ️ www.varianteffect.org/seminar-seri...

Ever wondered how your genes shape your health? Dive into the Variants and Us (VUS) Podcast—where cutting-edge science meets real-world impact.
🎧 varianteffect.org/podcast/
#Genetics #RareDisease #VariantEffect #SciencePodcast #PersonalizedMedicine

Multiplexed assays of variant effect for clinical variant interpretation Nature Reviews Genetics - Multiplexed assays of variant effect (MAVEs) are highly scalable experimental approaches used to generate functional data for genetic variants. In this Review, McEwen et...

Interested in using functional data to understand clinical variants? Been hunting for a good review of the topic? We just wrote one! rdcu.be/exaEU

🚨In this issue🚨
A trio of papers provide key insights for integrating functional data into clinical variant interpretation
#MAVE #VUS
@dougfowler.bsky.social @clareturnbull.bsky.social @leastarita.bsky.social @gregfindlay.bsky.social @afrubin.bsky.social

🚨 Most variant screens measure growth or abundance. What do they miss? That variants impact a spectrum of protein and cellular phenotypes. Variant in situ sequencing (VIS-seq) finds what’s missing: image cells 🔬 first, decode later, revealing multi-scale phenotypes for thousands of variants.👇

1/9

Cartoon showing a woman looking in to a microscope saying "Whoaah!!!" The caption states "The best part of Science is knowing, for a moment, something that nobody else in the world knows"

A reminder in these hard times. #sciencestrong

Insights on improving accessibility and usability of functional data to unlock their potential for variant interpretation Variant-level functional data are a core component of clinical variant classification and can aid in reinterpreting variants of uncertain significance…

Exciting recent work from colleagues @leastarita.bsky.social and Andrew Stergachis surveying clinical variant interpreters on the use of functional data!

TLDR: huge demand for functional data WITH standardization, quality metrics, and better access.

@ajhgnews.bsky.social
shorturl.at/f8N4A

TOMORROW - June 3 - at 9 AM - The Variant Effects Seminar Series will feature Ben Li (U of Michigan) & Vahid Aslanzadeh (U of Edinburgh) Details: www.varianteffect.org/seminar-seri...
@varianteffect.bsky.social
@uwmedicine.bsky.social

Build power, protect science! Thanks @sufsseattle.bsky.social @standupforscience.bsky.social

'Science can feel like magic. When you begin to understand how and why things work, it’s incredible.'
Learn more about Katie Partington, an 'intellectually adventurous' promising young scientist in the lab of BBI's Dr. Doug Fowler.
brotmanbaty.org/news/promisi...
@dougfowler.bsky.social
@hmc.edu

So excited for and proud of @muffley.bsky.social!!! Since she joined our team, she's accomplished the impossible, knitting together international collaborations, empowering our team and making everything sing. We're so lucky to work with her!!!

Thanks to @cegs-cmap.bsky.social @brotmanbaty.bsky.social @chanzuckerberg.bsky.social and others for support!!!

end

@danweihuangfu.bsky.social @benlehner.bsky.social ner.bsky.social @travelingeneticist.bsky.social @anneotation.bsky.social sky.social @poseypod.bsky.social ky.social @leastarita.bsky.social starita.bsky.social @hyejungwon.bsky.social won.bsky.social @heidirehm.bsky.social

And many others!!!

6/n

Thanks to all who attended the meeting and worked on the ideas! @mehurles.bsky.social @davidjadams.bsky.social @muffley.bsky.social @ewanbirney.bsky.social @nadavahituv.bsky.social @bennibolo.bsky.social @johndoench.bsky.social @ee-reh-neh.bsky.social @amglazer.bsky.social

5/n

The roadmap lays out how we get there, with heaps of data production, amazing new technologies, international coordination and clinical implementation

4/n

We came up with 2 key goals for 2030:

-resolve variants of uncertain significance ~1000 high need genes using at-scale variant effect experiments and models

-measuring the full stack of molecular and cellular phenotypes associated with disease-causing variants in a smaller set of genes

3/n

Last year, we convened a group of researchers, clinicians and others in Pittsburgh to craft a plan to measure and model the effects of all possible variants in human genes and regulatory regions

2/n

Our "Atlas of Variant Effects 2030 Roadmap" is live: zenodo.org/records/1542...

1/n

Led by @vvouts.bsky.social in @rhp-lab.bsky.social, we measured the degron potency of >200,000 30-residue tiles from >5,000 cytosolic human proteins and trained an ML model for degrons

📜 www.biorxiv.org/content/10.1...
🖥️ github.com/KULL-Centre/...

Coming up in June! You can find more information on our website www.varianteffect.org

Are you or someone you know affected by Hemophilia B? BBI's Drs. Jill Johnsen & Doug Fowler have advanced genetic understandinng of the blood disorder. Learn more.
brotmanbaty.org/news/new-mut...
@uwmedicine.bsky.social
@dougfowler.bsky.social
@hemophilia.bsky.social

the word alert is in a purple circle ALT: the word alert is in a purple circle

ACTION ITEM-----ACTION ITEM

Implementation of Schedule F

This is what a lot of us have been worried about.

This allows for many civil service positions to replaced with political appointees. This could include NIH institute directors and even POs.

BUT THERE IS A COMMENT PERIOD...

1/n

MPRAbase (mprabase.ucsf.edu) , a customized database for massively parallel reporter assays (MPRAs) to easily find and download MPRA data. Amazing work by Jingjing Zhao, Fotis Baltoumas, Georgios Pavlopoulos, @vagar.bsky.social, ilias Georgakopoulos-Soares & others.

genome.cshlp.org/content/earl...

Guidelines for releasing a variant effect predictor - Genome Biology Computational methods for assessing the likely impacts of mutations, known as variant effect predictors (VEPs), are widely used in the assessment and interpretation of human genetic variation, as well...

New paper out in Genome Biology! 🎉
We lay out best-practice guidelines for releasing variant effect predictors, developed through the Atlas of Variant Effects Alliance @varianteffect.bsky.social

Open, interpretable, and clinically useful VEPs are the goal.

📄 doi.org/10.1186/s130...

My guidelines for exploratory data analysis