A foldamer ligand demonstrates drug-like properties and rescues synucleinopathy disease phenotypes in multiple in vitro and in vivo models
www.science.org/doi/10.1126/...

SNP calling, haplotype phasing and allele-specific analysis with long RNA-seq reads Nature Methods - In this study, long-read RNA sequencing achieves accurate single-nucleotide polymorphism calling, haplotype phasing and allele-specific expression analysis.

LongcallR for competitive SNP calling and haplotype phasing, and simplified allele-specific analysis with long RNA-seq reads. Found ~100 junctions affected by SNPs per sample with most junctions novel.

Developed by Neng Huang. Published in @natmethods.nature.com. Read at rdcu.be/faKhL

Clinical evidence yield as a framework for evaluating computational predictors and multiplexed assays of variant effect www.biorxiv.org/content/10.64898/2026.03...

Explore live radio by rotating the globe Explore live radio by rotating the globe.

Your periodic reminder that there is a website that lets you listen to local radio stations anywhere in the world

This is honestly one of the coolest inventions ever, imo. Global access to hyper-local imagined communities

👀 Absolute banger paper. Leveraging cattle/pig GWAS/eQTL to help explain the missing regulatory gap in humans. Consistent with previous works, selection makes identifying relevant eQTLs in humans challenging.

www.biorxiv.org/content/10.6...

Threaded below for your convenience, if you're one of those people who does not live online on weekends!

(Also my hair looks great thanks for asking)

A new preprint from IGVF introduces a scalable workflow to address variants of uncertain significance (VUS).

Across 40 genes, the approach reclassified 75% of 16,115 VUS and preclassified >90K variants—moving clinical genomics forward.

Read more: 
www.biorxiv.org/content/10.6...

Let's try this again 👋

Hi Bluesky - I'm Massachusetts' Attorney General. You might know me from suing President Trump nearly 50 times, beating Uber and Lyft in court, or being the first woman of color elected to statewide office in MA.

I officially left X today - help me find my MA people?

Genetic underpinnings of chills from art and music Author summary Many people experience chills when listening to music, reading poetry, or viewing art. Yet not everyone feels these reactions in the same way. These differences provide a window into ho...

A particular moment in my favourite Radiohead song always gives me goosebumps every time I play it. Turns out susceptibility to such “chills” (induced by music, poetry, art) varies between people & that genetic differences play a part. Check out our new paper, led by @giacomobignardi.bsky.social. 👇🧪

Missense variants in TUBA4A cause myo-tubulinopathies #RareDisease #Genetics #morbidgene #newphenotype academic.oup.com/brain/advanc...

✨ A new star allele was born! Excited to share our first in vivo pharmacokinetic recall study involving 114 participants from @ESTbiobank with previously uncharacterised variants in CYP2C19 and CYP2D6:
www.nature.com/articles/s41... #Pharmacogenomics @pharmvar.org @clinpgx.org

Our paper is (finally) out in Cell today!

CRISPR screens in iPSC-derived neurons reveal principles of tau proteostasis
www.cell.com/cell/fulltex...

Great collaborative effort - read more from first author @asamelson.bsky.social below:

Three open questions in polygenic score portability Nature Communications - Genetic predictors of health outcomes often drop in accuracy when applied to people dissimilar to participants of large genetic studies. Here, the authors investigate the...

Our work on the generalizability of polygenic scores (PGS) from the @arbelharpak.bsky.social Lab is now officially out!

We examine the accuracy of PGS predictions at the individual level. We make 3 observations that expose gaps in our understanding of PGS “portability.”

rdcu.be/e0LAr

(1/27)

Figure from: Joint modelling of whole genome sequence data for human height via approximate message passing

A new algorithm can jointly analyze tens of millions of genetic variants at once in whole genome sequence data. Applied to human height in UK Biobank, it reveals rare variants and achieves 46% prediction accuracy.

www.biorxiv.org/content/10.1101/2023.09....

Welcome to rv rv - A fast, declarative, R package manager

rv. like uv, but for #Rstats a2-ai.github.io/rv-docs/

I'm just delighted to announce our new preprint on genome-scale perturb-seq in CD4+ T cells. We learned both general lessons about the power of perturb-seq, and specific lessons about T cell biology.

Led by amazing postdocs Emma Dann and Ronghui Zhu, with my wonderful collaborator Alex Marson.

Heterozygous Loss of OSR2 Can Cause Radio-Ulnar Synostosis with Ancillary Skeletal Manifestations #RareDisease #Genetics #morbidgene www.sciencedirect.com:5037/science/arti...

As a (to me very enjoyable) part of this paper, we worked out what mutation-selection balance looks like in finite populations with varying degrees of inbreeding.

How do ARRB1 loss-of-function variants alter GLP-1R internalization and cAMP signaling, and do GLP1R Gly168Ser carriers show distinct weight-loss responses? Can polygenic models integrating GLP1R and ARRB1 predict long-term GLP-1RA efficacy across ancestries?

We are thrilled to announce the first official release (v0.1.8) of #𝗯𝗲𝗱𝗱𝗲𝗿, the successor to one of our flagship tool, #𝗯𝗲𝗱𝘁𝗼𝗼𝗹𝘀! Based on ideas we conceived of long ago (!), this was achieved thanks to the dedication of Brent Pedersen.

1/n

Determining the value of genomics in healthcare - Nature Medicine Assessing the value of genomics is key to informing evidence-based policies; this Review outlines how current approaches to health technology assessment, implementation and data management can be adap...

In this Nature Medicine paper, we draw from our experiences in evaluating and implementing #genomics in Australia, Canada, England, Hong Kong and the US

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

Editing stem cell genomes at scale to measure variant effects in diverse cell and genetic contexts Multiplexed assays of variant effect (MAVEs) systematically measure variant function but have been limited to cancer cell lines rather than disease-relevant cell types. We developed saturation genome ...

The effects of genetic variants primarily occur in differentiated cells meaning we need to access these cell types to measure variant effects for most disease genes. We developed saturation genome editing in stem cells (iPSC-SGE) to enable phenotyping in diverse genetic and cell contexts at scale!

The missing heritability question is now (mostly) answered Not with a bang but with a whimper

I wrote a little bit about the "missing heritability" question and several recent studies that have brought it to a close. A short 🧵

The amazing @shawnfayer.bsky.social has developed a saturation genome editing method in iPSCs enabling MAVEs in differentiated cell types and diploid contexts. Please check it out!
And, for some lucky department, Shawn is on the faculty job market!

🚨Big News!🚨
Our keynote lineup for the ASHG Genetic Diagnosis & Rare Disease Virtual Symposium is here!
Dec 2: @ahrensnicklas.bsky.social & @kiranmusunuru.bsky.social
Dec. 3: Helene Cederroth & Eric Klee
You won't want to miss their insights shaping rare disease genetics: bit.ly/3WVd6l2 #ASHG

Estimation and mapping of the missing heritability of human phenotypes - Nature WGS data were used from 347,630 individuals with European ancestry in the UK Biobank to obtain high-precision estimates of coding and non-coding rare variant heritability for 34 co...

First time on Bsky and first big announcement!

I am excited to announce that our new study explaining the missing heritability of many phenotypes using WGS data from ~347,000 UK Biobank participants has just been published in @Nature.

Our manuscript is here: www.nature.com/articles/s41....

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...

📍Pinned Post: Welcome to the papers with code feed!
bsky.app/profile/did:...

Papers from PubMed, bioRxiv, Bature, PLoS, etc, with links to GitHub will be included here. Anyone can post to this feed.

See also: blog.stephenturner.us

Partial STX11 deficiency due to a hypomorphic variant—self-limiting inflammatory disease preceding HLH onset | Journal of Human Immunity | Rockefeller University Press Recently developed in vitro technology was used to define the function of a previously uncharacterized STX11 mutation L135P present in a patient with atypi

Noori, Banday, Voskoboinik et al use recently developed in vitro technology to define the function of a previously uncharacterized STX11 mutation L135P in a patient w/ atypical familial hemophagocytic lymphohistiocytosis. rupress.org/jhi/article/...

🎥 See a video summary: youtu.be/cYSBIU0lh6U

Designing allosteric modulators to change GPCR G protein subtype selectivity - Nature Studies of the G-protein-coupled receptor NTSR1 show that the G protein selectivity of this receptor can be modified by small molecules, enabling the design of drugs that work by switching receptor su...

Now online @nature.com!

Want to change the consequences of receptor activation?

Small molecules binding the GPCR-transducer interface change G protein subtype preference in predictable ways, enabling rational drug design 💥

So many new possibilities! 🧪🧠🟦

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

🧵👇