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Ruby Dawes @ruebenadawes.bsky.social · Aug 29

Love when you can build a paper out of a personal bugbear! tl;dr the precomputed SpliceAI scores are great, but proceed with caution!

Alex Geary @alextremophile.bsky.social · Aug 29

I am super proud to present our new manuscript “Using SpliceAI to triage splice-altering variants in 7,220 individuals with rare conditions highlights limitations of the precomputed scores”
www.medrxiv.org/content/10.1...

Using SpliceAI to triage splice-altering variants in 7,220 individuals with rare conditions highlights limitations of the precomputed scores

Background: SpliceAI is a deep learning algorithm that predicts whether genetic variants are likely to affect splicing. Precomputed spliceAI predictions for all theoretical SNVs and small indels were ...

www.medrxiv.org

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Reposted by Ruby Dawes

Nicky Whiffin @nickywhiffin.bsky.social · Aug 29

So proud of two postdocs in the team @alextremophile.bsky.social and @ruebenadawes.bsky.social. My role here was one of 'chief cheerleader' with this work truly led by these two superstars 🤩

The key take-home: be careful when using SpliceAI precomputed scores. Why? Read Alex's 🧵to learn more.
🧬💻🩺

Alex Geary @alextremophile.bsky.social · Aug 29

I am super proud to present our new manuscript “Using SpliceAI to triage splice-altering variants in 7,220 individuals with rare conditions highlights limitations of the precomputed scores”
www.medrxiv.org/content/10.1...

Using SpliceAI to triage splice-altering variants in 7,220 individuals with rare conditions highlights limitations of the precomputed scores

Background: SpliceAI is a deep learning algorithm that predicts whether genetic variants are likely to affect splicing. Precomputed spliceAI predictions for all theoretical SNVs and small indels were ...

www.medrxiv.org

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Reposted by Ruby Dawes

Nicky Whiffin @nickywhiffin.bsky.social · Aug 18

🚨 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 @alexblakes.bsky.social · Aug 18

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

Biallelic variants in the non-coding RNA gene RNU4-2 cause a recessive neurodevelopmental syndrome with distinct white matter changes

Genetic variants in RNU4-2, which encodes U4, a key non-coding small nuclear RNA (snRNA) component of the major spliceosome, were recently shown to cause a prevalent neurodevelopmental disorder (NDD) ...

www.medrxiv.org

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Reposted by Ruby Dawes

alexblakes.bsky.social @alexblakes.bsky.social · Aug 18

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

Biallelic variants in the non-coding RNA gene RNU4-2 cause a recessive neurodevelopmental syndrome with distinct white matter changes

Genetic variants in RNU4-2, which encodes U4, a key non-coding small nuclear RNA (snRNA) component of the major spliceosome, were recently shown to cause a prevalent neurodevelopmental disorder (NDD) ...

www.medrxiv.org

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Reposted by Ruby Dawes

Nechama Wieder @nechamawieder.bsky.social · Jul 4

Super excited to share our new review paper - The role of untranslated region variants in Mendelian disease!
www.nature.com/articles/s41...

The role of untranslated region variants in Mendelian disease: a review - European Journal of Human Genetics

European Journal of Human Genetics - The role of untranslated region variants in Mendelian disease: a review

www.nature.com

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Reposted by Ruby Dawes

Nicky Whiffin @nickywhiffin.bsky.social · Jun 2

ReNU syndrome in yesterday's Washington Post ❤️

The amazing families are pushing to raise awareness. The article shows how important that awareness can be:

"His family just learned his diagnosis in April, thanks to a network of eagle-eyed moms". #mumPower

www.washingtonpost.com/dc-md-va/202...

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Reposted by Ruby Dawes

Nicky Whiffin @nickywhiffin.bsky.social · May 24

It's #eshg2025 #eshg25 time 🥳

Here is where you can catch the team over the next few days.

Please go and say hi!

A flyer advertising four talks and one poster:
Yuyang Chen - 11:30am Saturday 24th; talk (C01) - De novo variants in small open reading frames harbour new rare disease diagnoses
Anthony McGuigan - 6:45pm Saturday 24th; talk (C09) - Gene knockouts across 120,404 individuals for novel rare disease gene discovery
François Lecoquierre - 7:15pm Saturday 24th; talk (C09) - A map of predicted pseudoexons in human genes
Hyung Chul Kim - 1pm Sunday 25th; poster (P18.006.A) - Rare variant association study reveals small open reading frames (smORFs) as novel regulators of cardiometabolic diseases
Nicky Whiffin - 10:30am Monday 26th; talk (C29) - Saturation genome editing of RNU4-2 reveals distinct dominant and recessive neurodevelopmental disorders

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Ruby Dawes @ruebenadawes.bsky.social · May 15

thanks so much for having me jodie!

Jodie Ingles @jodieingles27.bsky.social · May 13

Super lucky to host the amazing @ruebenadawes.bsky.social today at Garvan! @garvaninstitute.bsky.social @nickywhiffin.bsky.social @dgmacarthur.bsky.social @ginaravenscroft.bsky.social #genesky

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Reposted by Ruby Dawes

Paul Gardner @ppgardne.bsky.social · Apr 30

Talk about impactful: ReNu syndrome linked to the RNU4-2 variation was discovered this time last year & now a global community has grown around those affected by the disease: www.renusyndrome.org/map

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Reposted by Ruby Dawes

Centre for Personalised Medicine @cpmoxford.bsky.social · Apr 10

Come and join us @stannescollege.bsky.social on Tuesday 29th April at 17:30 for an evening of talks on the discovery of ReNU syndrome, from the key people involved. Register here for your free place: cpm.ox.ac.uk/event/the-di...

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Reposted by Ruby Dawes

Anna Landre @annalandre.com · Jan 7

Do you know a UK-based wheelchair user who works in a lab and would be willing to user-test our prototype of what is believed to be the first-ever lab coat adapted for wheelchair users?

Please share far & wide! Interest form: forms.office.com/e/66FhcQjqRT

More info: www.ucl.ac.uk/ucl-east/new...

Two photos of Anna, a young white woman using an electric wheelchair, wearing a blue lab coat that fits her well with tables and dry-lab equipment in the background. Text reads: "A team of researchers and designers led by UCL is looking for wheelchair users working in wet lab environments to user-test what is believed to be the first-ever prototype of a lab coat adapted for wheelchair users."

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Reposted by Ruby Dawes

Alex Geary @alextremophile.bsky.social · Apr 14

I am delighted to share with you the news that our shiny new paper has hit the shelves in Genome Medicine!!

link.springer.com/article/10.1...

Key points (A 🧵):

Systematic identification of disease-causing promoter and untranslated region variants in 8040 undiagnosed individuals with rare disease - Genome Medicine

Background Both promoters and untranslated regions (UTRs) have critical regulatory roles, yet variants in these regions are largely excluded from clinical genetic testing due to difficulty in interpre...

link.springer.com

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Reposted by Ruby Dawes

Nicky Whiffin @nickywhiffin.bsky.social · Apr 11

🚨I could not be more excited to share our new preprint on saturation genome editing of the small nuclear RNA (snRNA) RNU4-2:
www.medrxiv.org/content/10.1...

A super fun collaboration with incredible duo @gregfindlay.bsky.social @joachimdejonghe.bsky.social from @crick.ac.uk
🧬🖥️🩺

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Saturation genome editing of RNU4-2 reveals distinct dominant and recessive neurodevelopmental disorders

Recently, de novo variants in an 18 nucleotide region in the centre of RNU4-2 were shown to cause ReNU syndrome, a syndromic neurodevelopmental disorder (NDD) that is predicted to affect tens of thous...

www.medrxiv.org

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Ruby Dawes @ruebenadawes.bsky.social · Apr 7

congrats jenny!

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Ruby Dawes @ruebenadawes.bsky.social · Mar 25

congrats gareth! very well deserved!!

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Reposted by Ruby Dawes

Nicky Whiffin @nickywhiffin.bsky.social · Mar 2

A few weeks ago, I had an incredibly emotional call with James Coney, a writer for the Sunday Times whose son Charlie was in the @genomicsengland.bsky.social 100k project and was recently diagnosed with ReNU syndrome. This beautiful article tells their story ❤️ www.thetimes.com/article/0bcc...

My son Charlie — and the breakthrough that changed our lives

James Coney and his wife, Sarah, struggled not knowing why their 12-year-old was born with a severe learning disability. In their darkest moments, they blamed themselves. Then, out of the blue, came a...

www.thetimes.com

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Ruby Dawes @ruebenadawes.bsky.social · Dec 18

it was lovely to have you christy!

Christy LaFlamme (she/her) @cwlaflamme.bsky.social · Dec 17

I want to extend a huge thank you to the @nickywhiffin.bsky.social lab for having me this past month to work on various projects using the @GenomicsEngland data. I learned a ton during my time @ox.ac.uk and continue to drink tea at least 3 times per day. Cheers!

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Ruby Dawes @ruebenadawes.bsky.social · Nov 22

The wonderful people I did my PhD with are looking for a bioinformatician to work on the ‘RNA for Rare Disease project’ (RNA4RD), in beautiful Sydney (best city in the world) - if you're in the market I can't recommend this opportunity enough!

www.linkedin.com

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Ruby Dawes @ruebenadawes.bsky.social · Nov 20

Congrats Emilie! Such a beautiful paper!

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Reposted by Ruby Dawes

Emilie Wigdor @emiliewigdor.bsky.social · Nov 20

📣 Big news! Our tag-team effort on common variants in rare neurodevelopmental conditions is now out in Nature 📣

Co-first authoring with the brilliant Qinqin Huang🌟—proof that teamwork does make the dream work. 💪 www.nature.com/articles/s41...

a couple of cartoon characters standing next to each other with one wearing a purple earring

Alt: a couple of cartoon characters standing next to each other with one wearing a purple earring

media.tenor.com

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Ruby Dawes @ruebenadawes.bsky.social · Nov 19

I'm going great thanks! Hopefully we can catch up sometime when we are in the same country 😂

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Ruby Dawes @ruebenadawes.bsky.social · Nov 19

Congrats huw!

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Ruby Dawes @ruebenadawes.bsky.social · Nov 18

lol thanks for exposing me @nickywhiffin.bsky.social ! Also it makes more sense when you see it with my messy desktop 😂

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Reposted by Ruby Dawes

Nicky Whiffin @nickywhiffin.bsky.social · Nov 11

Back home and reflecting on a fantastic week at #ASHG24.
It was wonderful to reconnect with friends, make new connections, and be surrounded by amazing science! 🧬

This was my first time attending ASHG with many of my amazing team (see below). They did an incredible job representing the group 🥰 1/2

Picture of six people smiling in the snow in the city of Denver

A picture of Yuyang Chen giving a presentation. In the background a large screen has a slide saying "Variants in RNU4-2 cause a neurodevelopmental disorder (ReNU syndrome)". In the foreground, many people sit listening to the talk.

A poster is being presented while others listen.

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