📣 Out now @naturemedicine.bsky.social 🧬🤖 👉 rdcu.be/fqasl Our automated reanalysis tool Talos enables broad adoption and delivers timely + equitable #raredisease #diagnosis at scale! ♻️ Runs monthly on >10K datasets 🎯High specificity 💰Low running costs 🤗Open source @dgmacarthur.bsky.social

I am happy to share the updated preprint of our TenK10K multiome project. tinyurl.com/tenk10k-mult.... The full caQTL summary from 922 donors and 3.5M nuclei is now available for download, plus many key summary results! Lots of new analyses since v1. Quick tour of what's changed 👇

Genetic regulation of cell type-specific chromatin accessibility shapes immune function and disease risk

Understanding how genetic variation influences gene regulation at the single-cell level is crucial for elucidating the mechanisms underlying complex diseases. However, limited large-scale single-cell ...

tinyurl.com

Angli Xue@anglixue.bsky.social · 11mo ago

New preprint alert: tinyurl.com/tenk10k-multiome. Excited to share our analysis on the impact of genetic variants on single-cell chromatin accessibility in blood, using scATAC-seq and WGS from over 1,000 donors and 3.5M nuclei as part of TenK10K phase 1 🧬 🧵👇 (1/n)

This mug should be awarded to every academic who served as department chair.

Super excited that our two companion papers on saturation genome editing (SGE) of RNU4-2 and discovery of a novel recessive neurodevelopmental disorder (NDD) were published yesterday 🥳 SGE experiment: www.nature.com/articles/s41... Recessive NDD characterisation: www.nature.com/articles/s41... 🧵

My day is summed up by this exchange with @dgmacarthur.bsky.social

What did the largest trial of an early detection of cancer blood test show? erictopol.substack.com/p/the-larges...

The Largest Study of a Multi-Cancer Early Detection Blood Test

Reviewing the new data and the "liquid biopsy" field

erictopol.substack.com

Planning your afternoon poster session at #ashg25? Come say hello! This is an amalgamation of our two recent preprints - working with @gregfindlay.bsky.social , @cassimons.bsky.social , @dgmacarthur.bsky.social and many others to study variation across RNU4-2 and describe a new recessive NDD 🧬

Awesome work by @zornitza.bsky.social and collaborators showing the immediate value of WGS for newborn screening in a cohort of 1,000 Australian babies. Now we need larger, more diverse cohorts to show this approach can achieve population scale!

Zornitza Stark@zornitza.bsky.social · 10mo ago

🤗 Out now @naturemedicine.bsky.social results of our genomic NBS study BabyScreen+ 👶🧬 👉 www.nature.com/articles/s41... 1,000 babies WGS using existing cards 600+ conditions 13 day TAT 16 diagnoses (vs 1 in std NBS) High clinical impact High parental acceptability

🤗 Out now @naturemedicine.bsky.social results of our genomic NBS study BabyScreen+ 👶🧬 👉 www.nature.com/articles/s41... 1,000 babies WGS using existing cards 600+ conditions 13 day TAT 16 diagnoses (vs 1 in std NBS) High clinical impact High parental acceptability

In these dark times, it comes as a rare pleasure to highlight @natanaels.bsky.social ‬ & @marcdemanuel.bsky.social's work on germline and somatic mutations in humans. 1/n www.biorxiv.org/cgi/content/...

Collateral mutagenesis funnels multiple sources of DNA damage into a ubiquitous mutational signature

Mutations reflect the net effects of myriad types of damage, replication errors, and repair mechanisms, and thus are expected to differ across cell types with distinct exposures to mutagens, division ...

biorxiv.org

And now the fourth preprint from the TenK10K phase 1 dataset, led by @anglixue.bsky.social from @drjosephpowell.bsky.social's team - looking at genetic impacts on cell type-specific chromatin accessibility in 1,000 individuals who also have WGS and scRNA-seq!

Angli Xue@anglixue.bsky.social · 11mo ago

New preprint alert: tinyurl.com/tenk10k-multiome. Excited to share our analysis on the impact of genetic variants on single-cell chromatin accessibility in blood, using scATAC-seq and WGS from over 1,000 donors and 3.5M nuclei as part of TenK10K phase 1 🧬 🧵👇 (1/n)

I think 182 year old research articles should be free I want to read about the man

One for the reading pile and this scQTL x Disease in a MR framework feels a v powerful approach (more tissues / cell types please!) -

Albert Henry@alberthenry.bsky.social · 11mo ago

1. 🚨New preprint: tinyurl.com/tenk10k-causal. We explored causal effects of gene expression in immune cell types on complex traits and diseases by combining single-cell expression quantitative trait loci (sc-eQTL) mapping in 5M+ cells from 1,925 donors in TenK10K study and GWAS. 🧵

Another preprint from the TenK10K program! This work, led by @alberthenry.bsky.social and Anne Senabouth, leverages the unprecedented power of this WGS/single cell RNA-seq cohort to explore causal influences of blood gene expression on immune diseases and traits. Thread:

Albert Henry@alberthenry.bsky.social · 11mo ago

1. 🚨New preprint: tinyurl.com/tenk10k-causal. We explored causal effects of gene expression in immune cell types on complex traits and diseases by combining single-cell expression quantitative trait loci (sc-eQTL) mapping in 5M+ cells from 1,925 donors in TenK10K study and GWAS. 🧵

Our latest research is out today on ‪@medrxivpreprint.bsky.social: www.medrxiv.org/content/10.1... Saturation genome editing of BRCA1 across cell types accurately resolves cancer risk. Led by the amazing Phoebe Dace. This one’s packed full of data, so check out the paper. Quick highlights… 🧵 1/n

Saturation genome editing of BRCA1 across cell types accurately resolves cancer risk

Germline pathogenic BRCA1 variants predispose women to breast and ovarian cancer. Despite accumulation of functional evidence for variants in BRCA1 , over half of reported single-nucleotide variants (...

medrxiv.org

🚨 New preprint led by amazing duo @rociorius.bsky.social and @alexblakes.bsky.social in collaboration with @cassimons.bsky.social, @dgmacarthur.bsky.social and many other amazing folks! ❤️ We describe the clinical phenotype of a recessive NDD associated with biallelic variants in RNU4-2 🧬 See 🧵👇

@alexblakes.bsky.social · 12mo ago

I am absolutely delighted to share our work describing a new *recessive* condition caused by variants in #RNU4-2. Yes, that #RNU4-2! tinyurl.com/3j9r56s8 @rociorius.bsky.social @yuyangchen.bsky.social @gregfindlay.bsky.social @dgmacarthur.bsky.social @cassimons.bsky.social @nickywhiffin.bsky.social

New preprint! The outcome of a wonderful collaboration with @nickywhiffin.bsky.social’s team to define a new recessive syndrome associated with inherited variants in RNU4-2, the non-protein-coding gene that keeps on giving.

@alexblakes.bsky.social · 12mo ago

I am absolutely delighted to share our work describing a new *recessive* condition caused by variants in #RNU4-2. Yes, that #RNU4-2! tinyurl.com/3j9r56s8 @rociorius.bsky.social @yuyangchen.bsky.social @gregfindlay.bsky.social @dgmacarthur.bsky.social @cassimons.bsky.social @nickywhiffin.bsky.social

#HGSA2025 week kicks off with the OurDNA symposium tomorrow (with a preview of the OurDNA browser!) Register to attend online here👇

Daniel MacArthur@dgmacarthur.bsky.social · last yr.

Hey Australian genetics/genomics friends: the OurDNA Symposium will be in Sydney on 14 August, just before the HGSA meeting. Learn more about inclusive recruitment for genomics and get a preview of the OurDNA variant browser! events.humanitix.com/ourdna-sympo...

📣 We are recruiting! Please share!! Are you a bioinformatician / computational scientist who wants to apply your skills to understanding regulatory biology and improving rare disease diagnosis and treatment? 🧠 💻 🧬 🩺 We have two roles available 👇 🧵 1/4

Leena Peltonen School of Human Genetics in full-swing! @gosiatrynka.bsky.social @dgmacarthur.bsky.social @bpasaniuc.bsky.social @tuuliel.bsky.social @hilarycmartin.bsky.social @sashagusevposts.bsky.social @zkutalik.bsky.social @mashaals.bsky.social @alemedinarivera.bsky.social

This implies there is a huge literature of small microbiome association studies that is JUST NOISE. (As observed for these other fields)

About a hundred reasons not to use Excel. Yes, these are politely described as 'spreadsheet' horror stories, but we all know which bit of software we're really talking about. (HT @pgmj.bsky.social)

Peer review is not quite dead but it’s on life support and the current model of scientific publishing is a burning platform. healthydebate.ca/2025/06/topi...

Is peer-review dead? A scientist’s plea to fix a broken system - Healthy Debate

Peer-review may not be over, but the era of exploitative, opaque and corporatized gatekeeping should be.

healthydebate.ca

Preprint out today! A team led by @tobioinformatics.bsky.social and Bradley Harris in @carlanderson.bsky.social ‘s lab has created the largest single-cell atlas of IBD tissues to date www.medrxiv.org/content/10.1...

Hey Australian genetics/genomics friends: the OurDNA Symposium will be in Sydney on 14 August, just before the HGSA meeting. Learn more about inclusive recruitment for genomics and get a preview of the OurDNA variant browser! events.humanitix.com/ourdna-sympo...

OurDNA Symposium 2025: Partnering for impact

The OurDNA Symposium brings stakeholders together for important conversations about building the foundation for equitable genomics in Australia.

events.humanitix.com

I wrote a new piece on how much progress has been made in treating childhood leukemia. The answer is: quite a lot! Before the 1970s, fewer than 10% of children diagnosed survived 5 years after diagnosis. Now most are cured and around 85% survive that long. ourworldindata.org/childhood-le...

I worry that not enough of a big deal is being made about how long-term the devastation of these budget cuts to our scientific and health agencies will be, beyond the absolute ruin they will cause in the acute period.

Flybase lost all of the NIH support overnight - it is a disaster for the community. Please consider donating. I just did! www.philanthropy.cam.ac.uk/give-to-camb...

Drosophila Genetic Database

The Drosophila Genetic Database, FlyBase, is on the brink of collapse due to the sudden termination of the FlyBase NIH grant, which includes salaries for 5 literature curators based at the University ...

philanthropy.cam.ac.uk

Jesus. Excellent work by Michael Le Page, and utterly infuriating scenario. As Michael points out, the press release from Colossal called these dire wolves throughout. But now they want to argue that they never claimed that. Scandalous, really. www.newscientist.com/article/2481...

Colossal scientist now admits they haven’t really made dire wolves

Despite a huge media fanfare in which Colossal Biosciences claimed to have resurrected the extinct dire wolf, the company's chief scientist now concedes that the animals are merely modified grey wolve...

newscientist.com