Nicky Whiffin
@nickywhiffin.bsky.social
Associate Professor @ Big Data Institute, University of Oxford
2024 Lister Institute Fellow
genomics | rare disease | gene regulation | genetic therapies
https://rarediseasegenomics.org/
(field) hockey player | cyclist | hiker
2024 Lister Institute Fellow
genomics | rare disease | gene regulation | genetic therapies
https://rarediseasegenomics.org/
(field) hockey player | cyclist | hiker
Feeling exhausted after a fantastic but (as always) full-on #ashg25 . Great to catch-up with so many folks!
So long Boston, for a little while at least...
So long Boston, for a little while at least...
October 18, 2025 at 8:53 PM
Feeling exhausted after a fantastic but (as always) full-on #ashg25 . Great to catch-up with so many folks!
So long Boston, for a little while at least...
So long Boston, for a little while at least...
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 🧬
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 🧬
October 16, 2025 at 2:55 PM
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 🧬
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 🧬
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 ❤️
2/3
(1) showing just how many new diagnoses are found across these genes ❤️
2/3
September 8, 2025 at 8:43 AM
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 ❤️
2/3
(1) showing just how many new diagnoses are found across these genes ❤️
2/3
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)
🤯🤓🧬❤️
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)
🤯🤓🧬❤️
August 18, 2025 at 2:03 PM
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)
🤯🤓🧬❤️
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)
🤯🤓🧬❤️
📣 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
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
July 31, 2025 at 4:12 PM
📣 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
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
I also couldn't resit embracing the new #blue4ReNU awareness campaign with some (very) blue nails 💅
(although I am now realising that I have limited my wardrobe choices for a while...)
(although I am now realising that I have limited my wardrobe choices for a while...)
July 28, 2025 at 9:03 AM
I also couldn't resit embracing the new #blue4ReNU awareness campaign with some (very) blue nails 💅
(although I am now realising that I have limited my wardrobe choices for a while...)
(although I am now realising that I have limited my wardrobe choices for a while...)
Last week was the first #ReNUhopeConference
It was an enormous privilege to meet many ReNU warriors (they give the best hugs!) and their families, and scientists and clinicians working on ReNU.
ReNU Syndrome United have achieved so much in only a single year, building an incredible community 💙
It was an enormous privilege to meet many ReNU warriors (they give the best hugs!) and their families, and scientists and clinicians working on ReNU.
ReNU Syndrome United have achieved so much in only a single year, building an incredible community 💙
July 28, 2025 at 9:03 AM
Last week was the first #ReNUhopeConference
It was an enormous privilege to meet many ReNU warriors (they give the best hugs!) and their families, and scientists and clinicians working on ReNU.
ReNU Syndrome United have achieved so much in only a single year, building an incredible community 💙
It was an enormous privilege to meet many ReNU warriors (they give the best hugs!) and their families, and scientists and clinicians working on ReNU.
ReNU Syndrome United have achieved so much in only a single year, building an incredible community 💙
Huge bonus of a hybrid conference - even if you have to fly home, you can log on to listen to two amazing and inspiring award lectures!
Including from my absolutely incredible mentor, collaborator, and friend @dgmacarthur.bsky.social 🤩👏
Importantly, accompanied by a proper cup of tea 😊
#eshg2025
Including from my absolutely incredible mentor, collaborator, and friend @dgmacarthur.bsky.social 🤩👏
Importantly, accompanied by a proper cup of tea 😊
#eshg2025
May 27, 2025 at 1:02 PM
Huge bonus of a hybrid conference - even if you have to fly home, you can log on to listen to two amazing and inspiring award lectures!
Including from my absolutely incredible mentor, collaborator, and friend @dgmacarthur.bsky.social 🤩👏
Importantly, accompanied by a proper cup of tea 😊
#eshg2025
Including from my absolutely incredible mentor, collaborator, and friend @dgmacarthur.bsky.social 🤩👏
Importantly, accompanied by a proper cup of tea 😊
#eshg2025
Thank you Milan and #eshg2025, you have been fab!
Getting out early as two back-to-back meetings is a little too intense for me.
Great to catch up with so many, and sorry to everyone I missed this time out.
Looking forward to being back in my own bed!
Getting out early as two back-to-back meetings is a little too intense for me.
Great to catch up with so many, and sorry to everyone I missed this time out.
Looking forward to being back in my own bed!
May 26, 2025 at 3:30 PM
Thank you Milan and #eshg2025, you have been fab!
Getting out early as two back-to-back meetings is a little too intense for me.
Great to catch up with so many, and sorry to everyone I missed this time out.
Looking forward to being back in my own bed!
Getting out early as two back-to-back meetings is a little too intense for me.
Great to catch up with so many, and sorry to everyone I missed this time out.
Looking forward to being back in my own bed!
May 25, 2025 at 8:32 AM
After a fantastic few days at #VariantEffect25 in beautiful Barcelona (see below), now hopping my way to Milan for #ESHG25 #ESHG2025.
Looking forward to catching up with everyone 🧬🤓
Looking forward to catching up with everyone 🧬🤓
May 23, 2025 at 8:46 AM
After a fantastic few days at #VariantEffect25 in beautiful Barcelona (see below), now hopping my way to Milan for #ESHG25 #ESHG2025.
Looking forward to catching up with everyone 🧬🤓
Looking forward to catching up with everyone 🧬🤓
Tag teaming workshops on variant interpretation with one of my favourite humans @ksamocha.bsky.social in an Italian castle surrounded by frescos #bertinoro 🇮🇹 @eshg.bsky.social @deciphergenomics.bsky.social
May 8, 2025 at 2:11 PM
Tag teaming workshops on variant interpretation with one of my favourite humans @ksamocha.bsky.social in an Italian castle surrounded by frescos #bertinoro 🇮🇹 @eshg.bsky.social @deciphergenomics.bsky.social
#thatOxfordLife
Cycling through the tiny old streets of Oxford yesterday on my way to the @cpmoxford.bsky.social event on ReNU syndrome @stannescollege.bsky.social
Although staying true to my roots as always with my Cambridge blue / @caiuscollege.bsky.social Green Brompton 💙💚
Cycling through the tiny old streets of Oxford yesterday on my way to the @cpmoxford.bsky.social event on ReNU syndrome @stannescollege.bsky.social
Although staying true to my roots as always with my Cambridge blue / @caiuscollege.bsky.social Green Brompton 💙💚
April 30, 2025 at 10:41 AM
#thatOxfordLife
Cycling through the tiny old streets of Oxford yesterday on my way to the @cpmoxford.bsky.social event on ReNU syndrome @stannescollege.bsky.social
Although staying true to my roots as always with my Cambridge blue / @caiuscollege.bsky.social Green Brompton 💙💚
Cycling through the tiny old streets of Oxford yesterday on my way to the @cpmoxford.bsky.social event on ReNU syndrome @stannescollege.bsky.social
Although staying true to my roots as always with my Cambridge blue / @caiuscollege.bsky.social Green Brompton 💙💚
Friday timeline cleanse - the beautiful colours of UK spring 💙💜
April 25, 2025 at 8:55 AM
Friday timeline cleanse - the beautiful colours of UK spring 💙💜
What my husband sent me when I first told him about this result 🙄
(he is upset I didn't include it in my original thread 😂)
(he is upset I didn't include it in my original thread 😂)
April 14, 2025 at 2:42 PM
What my husband sent me when I first told him about this result 🙄
(he is upset I didn't include it in my original thread 😂)
(he is upset I didn't include it in my original thread 😂)
The regions where these variants are located are where (sometimes exact!) equivalent variants in RNU4ATAC cause recessive RNU4atac-opathies.
Hence, we suspect the mechanism may be distinct too…
ReNU syndrome: altered 5’ splice site usage
RNU4atac: intron retention
10/12
Hence, we suspect the mechanism may be distinct too…
ReNU syndrome: altered 5’ splice site usage
RNU4atac: intron retention
10/12
April 11, 2025 at 10:00 AM
The regions where these variants are located are where (sometimes exact!) equivalent variants in RNU4ATAC cause recessive RNU4atac-opathies.
Hence, we suspect the mechanism may be distinct too…
ReNU syndrome: altered 5’ splice site usage
RNU4atac: intron retention
10/12
Hence, we suspect the mechanism may be distinct too…
ReNU syndrome: altered 5’ splice site usage
RNU4atac: intron retention
10/12
But our insights are not limited to ReNU syndrome. We identified additional variants - in four linear regions of RNU4-2 - in which variants also had significant function scores (see red arrows below).
But unlike ReNU variants most of these variants are also observed in population cohorts 🤔
8/12
But unlike ReNU variants most of these variants are also observed in population cohorts 🤔
8/12
April 11, 2025 at 10:00 AM
But our insights are not limited to ReNU syndrome. We identified additional variants - in four linear regions of RNU4-2 - in which variants also had significant function scores (see red arrows below).
But unlike ReNU variants most of these variants are also observed in population cohorts 🤔
8/12
But unlike ReNU variants most of these variants are also observed in population cohorts 🤔
8/12
By splitting ReNU syndrome variants into those with strong signals of depletion and those with more moderate scores (grey dotted line in plot above) we show that SGE scores discriminate variants by phenotypic severity (thank you Elsa Leitão, @christeldepienne.bsky.social , Caroline Nava!).
7/12
7/12
April 11, 2025 at 10:00 AM
By splitting ReNU syndrome variants into those with strong signals of depletion and those with more moderate scores (grey dotted line in plot above) we show that SGE scores discriminate variants by phenotypic severity (thank you Elsa Leitão, @christeldepienne.bsky.social , Caroline Nava!).
7/12
7/12
We use these data to redefine the ReNU syndrome CR at nucleotide resolution.
In two regions of 9 and 4 nts 84.3% (75/89) of tested variants, including all ReNU syndrome variants (red), have significant function scores (below black dashed line; function score < -0.39).
6/12
In two regions of 9 and 4 nts 84.3% (75/89) of tested variants, including all ReNU syndrome variants (red), have significant function scores (below black dashed line; function score < -0.39).
6/12
April 11, 2025 at 10:00 AM
We use these data to redefine the ReNU syndrome CR at nucleotide resolution.
In two regions of 9 and 4 nts 84.3% (75/89) of tested variants, including all ReNU syndrome variants (red), have significant function scores (below black dashed line; function score < -0.39).
6/12
In two regions of 9 and 4 nts 84.3% (75/89) of tested variants, including all ReNU syndrome variants (red), have significant function scores (below black dashed line; function score < -0.39).
6/12
SGE function scores accurately discriminate ReNU syndrome variants from those observed in population cohorts (AUC=0.95) enabling us to resolve variant pathogenicity.
We massively outperform in silico tool CADD (AUC=0.65) which struggles due to high cross-species conservation across RNU4-2.
5/12
We massively outperform in silico tool CADD (AUC=0.65) which struggles due to high cross-species conservation across RNU4-2.
5/12
April 11, 2025 at 10:00 AM
SGE function scores accurately discriminate ReNU syndrome variants from those observed in population cohorts (AUC=0.95) enabling us to resolve variant pathogenicity.
We massively outperform in silico tool CADD (AUC=0.65) which struggles due to high cross-species conservation across RNU4-2.
5/12
We massively outperform in silico tool CADD (AUC=0.65) which struggles due to high cross-species conservation across RNU4-2.
5/12
A moment of appreciation for the incredible experimental skills of @gregfindlay.bsky.social and @joachimdejonghe.bsky.social - absolute SGE wizards 🪄!!
They devised an approach to deal with high sequence homology of U4 genes.
The resulting data are absolutely beautiful 😍
4/12
They devised an approach to deal with high sequence homology of U4 genes.
The resulting data are absolutely beautiful 😍
4/12
April 11, 2025 at 10:00 AM
A moment of appreciation for the incredible experimental skills of @gregfindlay.bsky.social and @joachimdejonghe.bsky.social - absolute SGE wizards 🪄!!
They devised an approach to deal with high sequence homology of U4 genes.
The resulting data are absolutely beautiful 😍
4/12
They devised an approach to deal with high sequence homology of U4 genes.
The resulting data are absolutely beautiful 😍
4/12
This preprint describes saturation genome editing (SGE) of RNU4-2: all possible SNVs across the 145-nt transcript, and all single nt insertions/deletions in the 18-nt CR.
We measure variants’ effects on cell fitness in the haploid cell line Hap1, with each variant given a ‘function score’.
3/12
We measure variants’ effects on cell fitness in the haploid cell line Hap1, with each variant given a ‘function score’.
3/12
April 11, 2025 at 10:00 AM
This preprint describes saturation genome editing (SGE) of RNU4-2: all possible SNVs across the 145-nt transcript, and all single nt insertions/deletions in the 18-nt CR.
We measure variants’ effects on cell fitness in the haploid cell line Hap1, with each variant given a ‘function score’.
3/12
We measure variants’ effects on cell fitness in the haploid cell line Hap1, with each variant given a ‘function score’.
3/12
It seems very appropriate for #IWD25 #internationalWomensDay to have spent the morning sharing a hockey pitch with this amazing bunch of women, who are so important for my mental health. A 4-0 win was the icing on the 🍰! 🏑
March 8, 2025 at 1:38 PM
It seems very appropriate for #IWD25 #internationalWomensDay to have spent the morning sharing a hockey pitch with this amazing bunch of women, who are so important for my mental health. A 4-0 win was the icing on the 🍰! 🏑