Jingyou Rao

A wonderful first for me at the upcoming @biophysicalsoc.bsky.social meeting in SF is having many lab members present! See 6 brilliant graduate students postdocs from the lab present talks and posters on how they are pushing the boundaries of technology and mechanistic membrane protein biology

Two #CRISPR talks on Feb3!
1️⃣ Stephan Riesenberg (Group Leader, Max Planck Leipzig): CRISPR-mediated generation of genetic variants for functional analysis.
2️⃣ Yuriy Baglaenko @baglaenkolab.bsky.social: Causal variants with CRISPR editing in primary human cells www.varianteffect.org/seminar-seri...

Specificity, length and luck drive gene rankings in association studies - Nature Genetic association tests prioritize candidate genes based on different criteria.

How do GWAS and rare variant burden tests rank gene signals?

In new work @nature.com with @hakha.bsky.social, @jkpritch.bsky.social, and our wonderful coauthors we find that the key factors are what we call Specificity, Length, and Luck!

🧬🧪🧵

www.nature.com/articles/s41...

🎙️ Next up Dec 2 in VESS!

Thea Schulze (Lindorff-Larsen Lab): Predicting mutated protein abundance @tkschulze.bsky.social

Taylor Mighell (Lehner Lab): Massive mutagenesis to understand GPCRs @taylor-mighell.bsky.social

🔗 More info at varianteffect.org/seminar-series
@varianteffect.bsky.social

🌏 🧬 Join the global functional genomics community in Melbourne this March for MSS26! The 9th Annual Mutational Scanning Symposium #VariantEffect26 runs March 25–27, 2026 at the Aikenhead Centre for Medical Discovery.
🗓️ Early bird registration & abstract submissions close Nov 2, 2025.
www.mss2026.org

Coming up next in the VESS (Nov 4):

Population genetics × variant effects:

🧬 Nikhil Milind (Stanford) on gene dosage and complex traits @nikhilmilind.dev
🧬 Leslie Smith (U Florida) on equitable ML in cancer genomics

www.varianteffect.org/seminar-seri...
@varianteffect.bsky.social

Postdoc Description.docx Title: Postdoctoral Associate Summary statement: The postdoctoral research associate is responsible for developing novel computational methodology for high-throughput sequence genomics tasks, as well ...

Have you recently completed (or finishing soon) a PhD in CS or a related discipline? Do you want to do research advancing the theory & practice of algorithmic genomics & build tools that people love to use? I'll be looking to hire a postdoc! Official ad coming soon:
docs.google.com/document/d/1...

VESS is happening tomorrow (Oct 7). See you there!
First speaker: Shelby Hemker (Dr. Jacob Kitzman Lab, University of Michigan)
Second speaker: Karl Romanowicz (Dr. Calin Plesa Lab, University of Oregon) @kroman.bsky.social
Link: www.varianteffect.org/seminar-seri...

The first (of hopefully many) reports to come from our collaboration with @hjp.bsky.social

We present a new type of cell fitness assay that allows you to both quantify and explain differences across human donors in cell proliferation and sensitivity to environmental toxicants.

Super excited to have this out. Thanks very much to the reviewers who helped improve this manuscript. Congrats to @jingyour.bsky.social!

bsky.app/profile/bioi...

We are excited to share GPN-Star, a cost-effective, biologically grounded genomic language modeling framework that achieves state-of-the-art performance across a wide range of variant effect prediction tasks relevant to human genetics.
www.biorxiv.org/content/10.1...
(1/n)

What we talk about when we talk about risk How embryo selection exploits our flawed intuitions about risk

I wrote about how genetic risk works in the context of embryo selection and how people often think about it all wrong. A short 🧵:

@jengreitz.bsky.social l & my lab want to co-hire a computational biologist/biostatistician with project management expertise to help map the regulatory code of the human genome and discover genetic mechanisms of disease.

Details below
careersearch.stanford.edu/jobs/computa...

Plz RT

Why yes! You can watch previous Variant Effects Seminar Series talks on our YouTube channel!
ℹ️ www.varianteffect.org/previous-sem... 📺 www.youtube.com/playlist?lis...

#Genomics #Seminar #EarlyCareerResearchers #ScientificSeminar #PrecisionMedicine

Very excited to have this out! Here, we take inspiration from model selection MR to decouple direct and indirect effects in DMS experiments. Check out Jingyou's explainer and paper below:

bsky.app/profile/jing...

Bittersweet to be leaving @docedge.bsky.social after a wonderful postdoc, but excited to share that I'm joining @uoregon.bsky.social next month as an Assistant Professor in the Department of Data Science.

GitHub - pimentellab/cosmos: A Position-Resolution Causal Model for Direct and Indirect Effects in Protein Functions A Position-Resolution Causal Model for Direct and Indirect Effects in Protein Functions - pimentellab/cosmos

Try Cosmos in Python now!
See vignettes to get started
🔗 Code: github.com/pimentellab/...

We applied Cosmos to 3 DMS datasets:
Kir2.1: abundance → surface expression
PDZ3: abundance → CRIPT binding
KRAS: abundance → RAF1_RBD binding
Cosmos clearly separates direct binding residues from those with indirect effects.
[6/n]

How does it work?
Cosmos aggregates mutation effects by position, learns interpretable causal graphs via Bayesian model selection, and outputs residue-level direct vs indirect effects.
[5/n]

Cosmos answers three key questions:
1️⃣ Is there a causal link between the phenotypes?
2️⃣ How strong is it?
3️⃣ What would the downstream phenotype look like if we “normalized” the upstream one (i.e., counterfactual inference)?
[4/n]

Cosmos is a Bayesian framework that performs residue-level causal inference to decouple how mutations influence upstream vs downstream functions.
No need for detailed biophysical models—just stats and data.
[3/n]

Multi-phenotype DMS experiments are revealing how mutations impact different protein functions.
But these phenotypes are often causally linked—e.g., when measuring activity, we may also capture effects propagated from abundance.
So how do we tell what’s direct vs indirect?
[2/n]

Cosmos: A Position-Resolution Causal Model for Direct and Indirect Effects in Protein Functions Multi-phenotype deep mutational scanning (DMS) experiments provide a powerful means to dissect how protein variants affect different layers of molecular function, such as abundance, surface expression...

How do we decouple the effects of two functional phenotypes in protein deep mutational scanning (DMS)?
Meet Cosmos, our new statistical framework for causal inference in multi-phenotype DMS.
www.biorxiv.org/content/10.1...
[1/n]

Trump freezes $200 million in UCLA science and medical research funding, citing antisemitism The Trump administration has frozen roughly $200 million in National Science Foundation, National Institutes of Health and other federal agency-funded research at UCLA, citing allegations the school d...

Suspension of all grants to UCLA www.latimes.com/california/s...

The 2026 Probabilistic Modeling in Genomics (ProbGen) meeting will be held at UC Berkeley, March 25-28, 2026. We have an amazing list of keynote speakers and session chairs:
probgen2026.github.io

Please help spread the news.

Perfect first day: receiving a set of new pipettes! Can’t wait to do more cool experiments with the lab for the next few years. @willowcoyote.bsky.social

Super proud of my first student, @jingyour.bsky.social! Well done! Looking forward to the amazing work you will do in the future 🥲 bsky.app/profile/jing...

Thrilled to share that I just successfully defended my PhD! Thanks to my committee, collaborators, and everyone who’d supported me throughout my seven years at UCLA. A special thank you to my PI Harold for his incredible mentorship! @hjp.bsky.social

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

Very excited to have this work out by @jeromics.bsky.social ! Please check it out.

I think my favorite story from the supplement is how impactful normalization can be in this context.

bsky.app/profile/jero...