Caroline Wright

another great international collaboration with our friends in UK and Australia to which we could contribute, describing a very unique disease mechanism for a novel neurodegenerative disorder #genetics #raredisease @ajhgnews.bsky.social @jamesfasham.bsky.social @rdexeter.bsky.social

@tm-yates.bsky.social @tisimpson.bsky.social

New machine learning method for automated extraction of gene-disease relationships from the literature using @gene2phenotype.bsky.social - should make future curation much faster, easier and more comprehensive, see preprint: www.medrxiv.org/content/10.1...

What do we mean by "actionability" in genomic medicine? An important question as we think more about using genomes for screening as well as diagnosis... read our new paper @gimjournal.bsky.social, authors.elsevier.com/a/1mBYc3vlFV...

Genotype-level quality control substantially reduces error rates in population-scale whole-genome sequencing Population-scale whole-genome sequencing data will contain many individual-level genotype errors, even after allele-level quality control (QC). We establish the need for genotype-level QC using UK Bio...

New paper on everyone’s favourite topic, QC!
We show why you should do genotype-level QC on your WGS data

www.biorxiv.org/content/10.1...

Very real quotes about this paper -
“The most exciting, mind-blowing paper of the year!”
“On a par with Fisher 1918”
“I read it every night. Just so beautiful”

Excellent autumnal away-day by the seaside with the Exeter genomics teams, organised by @drghawkes.bsky.social, discussing improvements to our whole genome sequence annotation and burden-testing pipelines - lots more exciting science to come! @exeter.ac.uk @nihrexeterbrc.bsky.social

Alistair Pagnamenta: rlReduced OI penetrance in @uk_biobank, implications for genomic newborn screening at #ICoNS25.

🦴 majority with P/LP variants have do not have multiple fractures

Impact on protein supported by proteomic data

👀 Preprint out today
www.medrxiv.org/content/10.1...

Reduced penetrance of COL1A1/2 pathogenic variants linked with osteogenesis imperfecta: analysis of a large population cohort Osteogenesis imperfecta (OI) is under consideration for inclusion in several genomic newborn screening initiatives, but its penetrance in clinically-unselected populations is currently unknown. It is ...

New pre-print on population penetrance - the first of a set exploring specific gene-disease pairs under consideration for genomic newborn screening. Spoiler alert: careful curation is essential, but penetrance is lower in population than clinical cohorts. www.medrxiv.org/content/10.1...

View of the River Exe running through the Quay in sunny Exeter.

Post-doc opportunity in Exeter 🌟 studying genetic modifiers of haemochromatosis 🩸

Closing date 30 Oct!

Come and work with a interdisciplinary team of epidemiologists, clinicians, and statistical geneticists, in a beautiful city in the South West of England ❤️

jobs.exeter.ac.uk/hrpr_webrecr...

Jane Goodall’s legacy: three ways she changed science The primatologist challenged what it meant to be a scientist.

As we mourn Jane Goodall, this @nature.com article explores three ways in which she changed science:

1. Altering the way we view both other primates and ourselves
2. Inspiring generations of women scientists
3. Communicating science in a way that engaged the public

www.nature.com/articles/d41...

Super-simple application of pathogenicity evidence during variant assessment in @deciphergenomics.bsky.social - even for complicated PVS1 in multiexon deletions where the frame is preserved - confirming a likely diagnosis.

Very cool new feature in @deciphergenomics.bsky.social - direct link from any missense variant to ProtVar @ebi.embl.org. This variant is in the binding site and likely interacts with the ligand, predicted using AlphaFold with AlphaFill!

Curiosity underlies a breakthrough in rare disease We must recognise and protect the pipelines that lead from research to real-world benefit

Both translational and fundamental curiosity-driven research are needed to fuel the incredible progress we're seeing in genomic medicine; an important message in this article and and some lovely quotes from @sarahlwynn.bsky.social
www.ft.com/content/25dd...

Pretty excited about giving Talos a try in the NHS @rdexeter.bsky.social‬. We should definitely be doing regular reanalysis of existing genome-wide sequencing data, just need the right tools!

So agree with this - Alphafold models are really fantastic for genomics researchers because they make mapping genetic variants so much simpler! But high-resolution experimental protein structures still offer important extra detail and accuracy, particularly for complexes, ligands, PTMs, etc.

Last day of #ESHG25 #ESHG2025, make sure to catch two fantastic back-to-back talks from @hls.exeter.ac.uk @drghawkes.bsky.social describing whole genome association analysis and meta-analysis across >500,000 people (Tuesday 11:15 & 11:30, C32)

OK, I'm starting to get #ESHG25 FOMO now! Those of you who are there should check out a poster from our group @hls.exeter.ac.uk investigating penetrance of variants in TSC1 & TSC2, with implications for newborn genome screening.(P15.033.D - pop by for a chat Monday 4-5pm)

At #ESHG25, make sure to hear the fantastic @chundru.bsky.social speak about characterizing genome-wide de novo mutations in control populations versus rare disease cases (Monday 11:15, C29), part of the work we're doing in paradigmgenomics.org

At #ESHG25, check out today's workshop with @jamesfasham.bsky.social to learn about the amazing @deciphergenomics.bsky.social‬ (Sunday 14:15, W10)

Got a big showing of talented University of Exeter scientists with talks and posters at ESHG25 in Milan. Come along and find out more! @hls.exeter.ac.uk @exeter.ac.uk #ESHG25 @jamesfasham.bsky.social @jingzhan.bsky.social @ambermluckett.bsky.social @chundru.bsky.social @harrygreentkd.bsky.social

Scalable automated reanalysis of genomic data in research and clinical rare disease cohorts Reanalysis of genomic data in rare disease is highly effective in increasing diagnostic yields but remains limited by manual approaches. Automation and optimization for high specificity will be necess...

🤗 Hugely excited to share our work on automating iterative reanalysis in #raredisease, preprint out: www.medrxiv.org/content/10.1... 🤖🧬

github.com/populationge...

A superb collaboration with @dgmacarthur.bsky.social @cassimons.bsky.social @heidirehm.bsky.social @ksamocha.bsky.social and many more!

Fascinating insights into embryonic life from a very productive collaboration between DECIPHER and MuzHaniffa and her talented team @mhaniffa.bsky.social

⬇️ again. I feel the need to re-post this point pretty much every week! Benign variants are not low penetrance.

"Remember that it's not only scientists that read your papers" - sage advice from author of a beautiful poem 'Proband', which began life as a response to our DDD NEJM paper, linking genomic science and its patients. www.consilience-journal.com/issue-17-pro...

Genetics, objectivity and a defence of DEI Genetics, both past and present, demonstrates a simple fact. DEI makes our science better.

A new post by me where I argue that genetics, both past and present, demonstrates a simple fact. DEI makes our science better.

open.substack.com/pub/jonathan...

Come and work with us - 2 Graduate Research Assistant positions available in genomic medicine, with a particular focus on variant interpretation and data analysis. Part of the Wellcome-funded PARADIGM project, and based in beautiful Exeter UK! jobs.exeter.ac.uk/hrpr_webrecr...

This is sad not just for genomics in the US, but across the world: Eric has been an incredibly effective global champion for the power of genomics and the impact of genomic medicine.

Lungfish xkcd.com/3064

Excellent trip to Sheffield for the UK Clinical Genetics Society Conference and National Dysmorphology Meeting. Lots of new ideas, lovely catching up with colleagues, and a bonus weekend walking in the sunny Peak District!

<blushes>... thanks Jeff, that's very kind 😊