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Nicky Whiffin

@nickywhiffin.bsky.social

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rarediseasegenomics.org

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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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Nicky Whiffin @nickywhiffin.bsky.social · 1d

She was fab! Sorry I couldn't stay for some 🍾

Reposted by Nicky Whiffin

Gautam Dey @gautamdey.bsky.social · 4d

If you’re applying to your dream lab for an internship/PhD/postdoc, always send a second email 1-2 weeks after the first one if you don’t hear back.

I promise we will be grateful rather than annoyed. My email inbox is a disaster and I’m quite junior - and very few of us have secretarial support

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Reposted by Nicky Whiffin

Bethany Brookshire @beebrookshire.bsky.social · 12d

In reporting this piece on the new trial for a Huntington's treatment, I was struck by one thing in particular:

The joy.

One of my sources wept for joy. He has spent his entire career studying this disease, he said it was the happiest day. www.sciencenews.org/article/hunt...

Huntington's progression slowed by experimental gene therapy

An experimental gene therapy slowed Huntington’s by up to 75 percent in a small clinical trial. While not a cure, it may give patients longer lives.

www.sciencenews.org

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Reposted by Nicky Whiffin

Greg Findlay @gregfindlay.bsky.social · Sep 8

We now have an open post-doc position in the lab:

crick.wd3.myworkdayjobs.com/External/job...

Please apply if you have a background in functional genomics or a related field and are eager to develop methods to map variant effects at scale.

crick.wd3.myworkdayjobs.com

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Nicky Whiffin @nickywhiffin.bsky.social · Sep 8

Not sure about long reads, but definitely higher depth and in more relevant cell types than the clinically accessible tissues we have so far. Hopefully there will be a useful biomarker too 🤞 Analysis tools more geared towards these subtle signatures would be helpful too!

Nicky Whiffin @nickywhiffin.bsky.social · Sep 8

@ewanbirney.bsky.social and @jeffbarrett.eu might be interested in this one. RNU2-2 (191 nts) is slightly longer than RNU4-2 (145 nts), but still pulling a lot of weight for diagnoses per base-pair 🤓

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Nicky Whiffin @nickywhiffin.bsky.social · Sep 8

(2) but even cooler is the flip of frequency between dominant and recessive forms in RNU4-2 and RNU2-2, driven by different signatures of mutation and selection - variants across RNU2-2 tend to be more common, driving a higher comp het frequency.

We have a lot to learn from these genes yet!!! 🧬🤓

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Nicky Whiffin @nickywhiffin.bsky.social · Sep 8

I absolutely love this figure in a second paper led by Adam Jackson, @alexblakes.bsky.social, and Sid Banka (www.medrxiv.org/content/10.1...) of RNU gene diagnoses in @genomicsengland.bsky.social 100k genomes project.

(1) showing just how many new diagnoses are found across these genes ❤️

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Two pie charts. On the left, a small segment of a grey pie chart labelled 'Unsolved NDD (N=7,968, 100%)' is shaded dark. A zoom out from this small segment shows individuals with new "RNU-opathies" in 100KGP (N=118, 1.48%). This has five segments, in order of size: (1) RNU4-2 dominant (N=59, 0.74%), (2) RNU2-2 recessive (N=38, 0.48%), (3) RNU2-2 dominant (N=11, 0.14%), (3) RNU4-2 recessive (N=5, 0.06%), (4) RNU5B-1 dominant (N=5, 0.06%).

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Nicky Whiffin @nickywhiffin.bsky.social · Sep 8

While I was taking a holiday last week, 2 super exciting preprints dropped, adding to another posted 6 days prior.

These papers describe a remarkable role for *recessive* variants in *RNU2-2* causing developmental and epileptic encephalopathy

🧵 by the amazing @christeldepienne.bsky.social 👇

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Christel Depienne @christeldepienne.bsky.social · Sep 5

After our study on RNU4-2 and RNU5B-1 published in May (Nava et al, Nature Genetics 2025), I am excited to share our new preprint reporting dominant and recessive variants in RNU2-2 as a frequent cause of developmental and epileptic encephalopathy (DEE).

📄 www.medrxiv.org/content/10.1...

Systematic analysis of snRNA genes reveals frequent RNU2-2 variants in dominant and recessive developmental and epileptic encephalopathies

Variants in spliceosomal small nuclear RNA (snRNA) genes RNU4-2 (ReNU syndrome), RNU5B-1 , and RNU2-2 have recently been linked to dominant neurodevelopmental disorders (NDDs), revealing a major, prev...

www.medrxiv.org

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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 Nicky Whiffin

yuyangchen.bsky.social @yuyangchen.bsky.social · Aug 26

1st Bluesky post with recent updates:
1/3 It was incredible to attend and speak at the ReNU Hope Conference in Long Island, NY. This was the first time I met the families and the ReNU warriors, sharing many touching stories. I hope to continue advocacy in China where few are currently diagnosed.

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Nicky Whiffin @nickywhiffin.bsky.social · Aug 21

👋

Susie Dent @susiedent.com · Aug 21

Word of the Day is ‘theic’ (19th century), defined as ‘one given to immoderate tea-drinking; a tea drunkard’.

Nicky Whiffin @nickywhiffin.bsky.social · Aug 20

Just over a week left to apply for these positions - deadline on Thursday 28th August 👇

Nicky Whiffin @nickywhiffin.bsky.social · Jul 31

📣 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 👇

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Image of an old building in Oxford with the heading 'postdoc opportunities' and the text 'computational approaches to improve rare disease diagnosis and treatment' and 'Big Data Institute, University of Oxford'

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Nicky Whiffin @nickywhiffin.bsky.social · Aug 19

The whole area around Harringay Green Lanes / Tottenham is just lies! (used to live near Turnpike Lane)

There is something very eye opening (and magical) the first time walking between two 'islands' the tube map fooled your brain into thinking were miles apart. Slowly piecing real London together ✨

Nicky Whiffin @nickywhiffin.bsky.social · Aug 19

One of the things I love about London are the regular street maps (at least anywhere near the center) which makes it easy to navigate without touching a phone.

My scout leader Dad would be very disappointed if I couldn't use a map 🗺️🧭

Reposted by Nicky Whiffin

Greg Findlay @gregfindlay.bsky.social · Aug 18

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 (...

www.medrxiv.org

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Nicky Whiffin @nickywhiffin.bsky.social · Aug 18

We are in safe hands with @gregfindlay.bsky.social , @leastarita.bsky.social , @dougfowler.bsky.social , Lizzie Radford, @mehurles.bsky.social and the Atlas of Variant Effects crew, but there is an awful long way to go!!!

Nicky Whiffin @nickywhiffin.bsky.social · Aug 18

Interesting idea Ewan! Tricky to calculate in a non-biased way though... 🤔

Nicky Whiffin @nickywhiffin.bsky.social · Aug 18

Isn't genetics cool???

Within only 145 nucleotides(!) of a non-coding RNA (RNU4-2) - different variants in distinct regions / structures cause three distinct disorders!!! (all discovered within the last 18 months)

🤯🤓🧬❤️

Schematic of the U4 and U6 snRNAs with coloured annotations to note nucleotides linked to different disorders:
- Teal in the T-loop and Stem III for ReNU syndrome (Chen et al. Nature 2024 and Greene et al. Nature Medicine 2024)
- Red for variants causing a recessive NDD in Stem II, the k-turn and Sm protein binding sites (De Jonghe et al. medRxiv 2025 and Rius & Blakes medRxiv 2025)
- Yellow for the central loop and Retinitis pigmentosa (Quinodoz et al. medRxiv 2025)

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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 Nicky Whiffin

Nicky Whiffin @nickywhiffin.bsky.social · Jul 31

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Reposted by Nicky Whiffin

Muzz Haniffa @mhaniffa.bsky.social · Aug 1

Great career opportunities in Cellular Genomics @sangerinstitute.bsky.social

Big data (human in vivo + in vitro) + AI to derive biological mechanisms at scale.

We are seeking a range of research expertise including spatial omics and perturbation at scale

Aidan Maartens @aidanmaartens.bsky.social · Jul 31

Group leader positions in @sangerinstitute.bsky.social Cellular Genomics, led by @mhaniffa.bsky.social, to decode and recode human tissues. Broad net - clinical research, in vitro models, single cell, AI. Vibrant, supportive community. Please share!

sanger.wd103.myworkdayjobs.com/en-GB/Wellco...

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Nicky Whiffin @nickywhiffin.bsky.social · Jul 31

🔵 We have a strong focus on professional and personal development and mentorship
🔵 We also do super cool science (at least I think so!!)

Find out more about us here: lnkd.in/dNfku6VS

If you are interested, feel free to reach out for a chat.

Links to apply in post 2 of this 🧵

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This link will take you to a page that’s not on LinkedIn

lnkd.in

Nicky Whiffin @nickywhiffin.bsky.social · Jul 31

Why should you join us?

🔵 We are a highly collaborative team with a passion about making a difference
🔵 We believe in science that is open, collaborative and reproducible
🔵 Our core values focus on kindness, inclusivity, curiosity, and supporting each other

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Nicky Whiffin @nickywhiffin.bsky.social · Jul 31

1️⃣ Early career postdoc: suitable if you have recently finished, or are finishing your PhD, or you have a degree & other (perhaps non-academic) research experience: lnkd.in/dikMam7R

2️⃣ A more senior position for those with post-PhD research experience (in any setting): lnkd.in/dqQsFCJx

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This link will take you to a page that’s not on LinkedIn

lnkd.in