🚨 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.👇

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Excited to share our @varianteffect.bsky.social CVI workstream preprint! Herein, we discuss important considerations for integration of multiplex functional data to generate a single score set and how this is likely to impact variant classification now and in the future

arxiv.org/abs/2503.18810

Excited to have this out as a preprint!

It was a pleasure to work with @calhoujd.bsky.social and all the coauthors brought together by @varianteffect.bsky.social.

Would love to see you all at the talk! Try the data out at one of the above annotators today! Watch out for the preprint in a couple weeks!
#ACMGMtg25 #AllofUs #GREGoR #medicalgenetics #raredisease #collaboration #annotation #exomes #genomes #sequencing #genetics #ineedtograduate #science
🧵 (4/4)

Want to hear more? I'll include this project in my talk this afternoon at #ACMG2025 🎤
🗓 Friday, March 21, 1:30 PM PST
📍 Platform Session 8: Genomic Medicine and Education
🎙 Talk: GREGoR: Accelerating Genomics for Rare Diseases

We’ve integrated the data for annotation of YOUR exomes and genomes into widely used mass annotators:
📌 ANNOVAR (Kai Wang)
📌 dbNSFP (Xiaoming Liu)
📌 Ensembl VEP (@malloryfreeberg.bsky.social; @ensembl.bsky.social; web interface coming soon!)
📌 OpenCRAVAT (@opencravat.bsky.social; Rachel Karchin)

🚨 Big news at #ACMG2025! 🚨
Today we’re announcing global democratization of deidentified allele count + frequency data with population breakdown from the first ~250k short-read WGS in All of Us designed to plug straight into clinical workflows. It is ~1.1 billion unique variants! 🧬💡
🧵 (1/4)

At #ACMG25? 🧬

Don't miss @moezdawood.bsky.social presenting "GREGoR: Accelerating Genomics for Rare Diseases"

Friday 3/20 at 1:30pm PST
Platform Session 8

Preprint here: pubmed.ncbi.nlm.nih.gov/39764392/

#Genomics #Research #Collaboration @gregor-research.bsky.social

In our updated TraitGym preprint (w/ @gonzalobenegas.bsky.social & Gökcen Eraslan), we evaluate Evo 2 on regulatory variants associated with human traits. We see marked performance gains with scale on Mendelian traits, although still a bit behind alignment-based methods.
doi.org/10.1101/2025...
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I'm very happy to share our latest work with Seth Berger and the UCI-GREGoR team. Using long-read sequencing, we can detect de novo variants *without* sequencing both parents. We call our method duoNovo.

preprint: www.medrxiv.org/content/10.1...
R package: github.com/sbergercnmc/...
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#standards, #mechanisms, & #identifiers - oh my!

Just in time for #RareDisease Day, the @gene2phenotype.bsky.social website has a fresh look & new features to improve access to gene-disease models. 🧬💻

👉 Updated website: www.ebi.ac.uk/gene2phenoty...
👉 Why it matters: www.ebi.ac.uk/about/news/u...

Interested in rare variants, the X-chromosome, sex-differences, pharmacogenetics, or transcription factors? You might be interested in our new manuscript where we identified >700 functional rare variants with a difference in effect by sex in GTEx! bit.ly/x_rv_sex #genomics #multiomics 💻🧬

A map of the rubisco biochemical landscape.

Rubisco is the main CO2-fixing enzyme of the biosphere yet its kinetics are slow. This work shows that non-trivial biochemical changes are readily accessible pointing the way to new engineering ways

🧪 @nature.com
www.nature.com/articles/s41...

Proud to introduce curated loci prime editing (cliPE)! It is a generalizable and accessible platform to characterize many genetic variants in a gene of interest 1/11
arxiv.org/abs/2501.04822

What if one variant can cause splicing outliers transcriptome-wide? In our preprint, we show how examining transcriptome-wide patterns of splicing outliers can both diagnose individuals with rare spliceopathies and uncover novel disease-gene relationships! (www.medrxiv.org/content/10.1...)

GREGoR Consortium preprint online! With the R02 release, there is a huge amount of genomics, multi-omics and phenotype data from the hardest-to-solve rare disease cases.

@meandertail.bsky.social, Michael Bamshad, @sbmontgom.bsky.social, @gregor-research.bsky.social

Chia-Lin Wei, Christopher Wellington, @mwheelermd.bsky.social, GREGoR Partner Members, @claucarvalho.bsky.social, @caseygifford.bsky.social, Susanne May, @danrdanny.bsky.social, @heidirehm.bsky.social, @sedlazeck.bsky.social, Eric Vilain, @anneotation.bsky.social, @poseypod.bsky.social,

Thanks to all the authors! Ben Heavner, Marsha Wheeler, @raungar.bsky.social, @realjlo.bsky.social, @laurensvdwiel.bsky.social, Seth Berger, Jon Bernstein, @jxchong.bsky.social, Emmanuèle C. Délot, Evan Eichler, Richard Gibbs, Jim Lupski, Ali Shojaie, Mike Talkowski, @alexphd.bsky.social,

Lots of hard work from many many people to realize the goals of moving rare disease genetics forward! Much more to come from GREGoR!

🚨 Excited to announce the Marker paper for the GREGoR Consortium! arxiv.org/abs/2412.14338

Accelerating #RareDisease diagnostics with cutting-edge #Genomics and global data sharing of omics and deep phenotyping from ~7500 individuals on NHGRI AnVIL and much more to come! 🧬

Genomic duplications involving MECP2 are surprisingly complex and affect almost half of patients. Importantly, complexity contributes to gene expression and clinical variability. @pnrigenetics.bsky.social @gregor-research.bsky.social genomemedicine.biomedcentral.com/articles/10....

Paper came out this past week! Using MAVEs to reduce variant classification disparities in underrepresented populations and demonstrating AI bias in computational predictors rdcu.be/d2kCn

Previous tweetorial: x.com/MoezDawood/s...

Previous post by @ee-reh-neh.bsky.social: bsky.app/profile/ee-r...

New work! Wherein we (as in, the AVE ODIC working group) looked at clinical variant classification across genetic ancestry groups in gnomAD and AoU and what we found... is exactly what you might expect, after decades of Eurocentric research. But we also show there's a better way forward! 🧬🖥️