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Alex Geary

@alextremophile.bsky.social
609 followers 487 following 40 posts

Postdoctoral Bioinformaticial in the Computational Rare Disease Genomics group (Nicky Whiffin). univ. Oxford 🧬💻 Loves Evolution, regulation, cheese and cats. She/Her

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Alex Geary @alextremophile.bsky.social · 04/09/2026
🎺 *fanfare* 📯 🚨 🎉 I am absolutely delighted to announce that we are recruiting for a PhD student to join the Fertility Research Edinburgh Supergroup (Myself, Margot Wyrwoll and Joris Veltman) 💫 at the university of Edinburgh. 🧬🧑‍🔬 ✨ institute-genetics-cancer.ed.ac.uk/igc-graduate...
institute-genetics-cancer.ed.ac.uk
Characterising the role of the spliceosome in dominant forms of monogenic male infertility | IGC Graduate Research & Training | Institute of Genetics and Cancer
Applications Now Open
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Alex Geary @alextremophile.bsky.social · 01/04/2026
I am excited to share that @wbickmor.bsky.social and I are offering a competitively funded PhD project on promoter diversity in vertebrates! www.findaphd.com/phds/project...
findaphd.com
EDCS - Understanding promoter diversity across vertebrates at University of Edinburgh on FindAPhD.com
PhD Project - EDCS - Understanding promoter diversity across vertebrates at University of Edinburgh, listed on FindAPhD.com
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Alex Geary @alextremophile.bsky.social · 02/03/2026
Know a super awesome postdoc who wants to come and work in a gorgeous city full of exciting science and wonderful people? We are recruiting! 💻 🧬🏴󠁧󠁢󠁳󠁣󠁴󠁿 elxw.fa.em3.oraclecloud.com/hcmUI/Candid...
elxw.fa.em3.oraclecloud.com
Post-Doctoral Research Associate in Computational Genomics
We are seeking a highly motivated Postdoctoral Research Associate in Computational Genomics to join our team at the University of Edinburgh. This is a unique opportunity to work on a cutting-edge proj...
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Institute of Genetics and Cancer @uoe-igc.bsky.social · 11/02/2026
Our final post for International Day of Women & Girls in Science is by @margotwyrwoll.bsky.social: "In my day-to-day work, I promote inclusion by mentoring early career researchers, being open about my own career path & advocating for fair recruitment and promotion processes." #EveryVoiceInScience
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Institute of Genetics and Cancer @uoe-igc.bsky.social · 06/01/2026
We are looking for the last ever intake of HGU PhD students to start in September. If you are passionate about biomedical research and are interested in doing a PhD, please apply by 11 January. Find out more here 👉 edin.ac/4srdd6t Apply here 👉https://edin.ac/49aBgPz
edin.ac
MRC four-year International PhD programme: Human Genetics, Genomics and Disease | IGC Graduate Research & Training | Institute of Genetics and Cancer
Applications now open.
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Alex Geary @alextremophile.bsky.social · 15/12/2025
Eeep! I can’t quite believe it! ♥️
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Alex Geary @alextremophile.bsky.social · 15/12/2025
Thanks Kaitlin! ♥️
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Alex Geary @alextremophile.bsky.social · 15/12/2025
It has been a big day, full of big emotions, but the biggest is the gratitude I feel to all the members of the CRDG, past and present, especially @nickywhiffin.bsky.social, and to @jorisveltman.bsky.social and @margotwyrwoll.bsky.social for already making me feel so welcome! 🧬Exciting times ahead!👩‍💻
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Alex Geary @alextremophile.bsky.social · 15/12/2025
I am SO excited to be joining the group of @jorisveltman.bsky.social where together with @margotwyrwoll.bsky.social we will focus on solving challenges in reproductive genomics and genomic medicine, and improving the lives of patients and their families.
Photographs of Joris Veltman and Margot Wyrwoll smiling
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Alex Geary @alextremophile.bsky.social · 15/12/2025
From January the first I will be taking my first steps into independence as the shiny new Lecturer in Computational Genomics, in the Institute of Genetics and Cancer (@uoe-igc.bsky.social) at the University of Edinburgh (@edinburgh-uni.bsky.social)
Purple logo of the Institute of genetics and cancer
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Alex Geary @alextremophile.bsky.social · 15/12/2025
In that time, under the phenomenal guidance of @nickywhiffin.bsky.social it has grown into a powerhouse of awesome science, empowerment and joy. I am devastated to be leaving, but am doing so with all the tools and support I need to succeed - a testament to Nicky's skills as a leader and mentor!
Photograph of Nicky Whiffin smiling in a snowy forest
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Alex Geary @alextremophile.bsky.social · 15/12/2025
It is a big day for me : a 🧵🪡 For the last five years I have had the absolute honour of being a postdoc in the 💜INCREDIBLE🩷 Computational Rare Disease Genomics group at the Nuffield Department of Medicine (@ndm.ox.ac.uk @ox.ac.uk), Uni. of Oxford (@ox.ac.uk).
Photograph of Computational Rare Disease Genomics group at a Christmas party.
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Alex Geary @alextremophile.bsky.social · 29/08/2025
And a special shout out to the absolutely awesome senior author on this - @ruebenadawes.bsky.social who was a total delight to work with from start to finish!
media.tenor.com
a cartoon character says you are my hero
ALT: a cartoon character says you are my hero
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Alex Geary @alextremophile.bsky.social · 29/08/2025
I would also like to thank all my co-authors for the time, effort and input that has made this a super little bit of work! I'm looking at you @francois-leco.bsky.social Suzi Walker and @nickywhiffin.bsky.social 👀
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Alex Geary @alextremophile.bsky.social · 29/08/2025
We would like to thank everyone who has contributed to this work, but most of all the team at Genomics England, all the participants and their families, without whom all this would not have been possible.
media.tenor.com
a man with long hair and a beard is smiling and saying thank you .
ALT: a man with long hair and a beard is smiling and saying thank you .
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Alex Geary @alextremophile.bsky.social · 29/08/2025
We therefore developed a command-line tool, ‘SpliceAI-splint’, to identify the subset of variants for which the precomputed scores may have decreased accuracy, to allow reannotation of a smaller overall variant set. github.com/Computationa...
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Alex Geary @alextremophile.bsky.social · 29/08/2025
These findings have real implications for the continued use of precomputed scores. However, despite these issues, precomputed scores still have substantial utility in limiting the computational resources required to identify predicted splice-altering variants.
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Alex Geary @alextremophile.bsky.social · 29/08/2025
By correcting these issues we found an increase of 18.2% predicted splice-altering variants compared with variants identified using precomputed scores alone. When assessed using diagnostic variants, updated SpliceAI scores resulted in a diagnostic increase of 11.7%.
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Alex Geary @alextremophile.bsky.social · 29/08/2025
To determine the potential impact of these issues we annotated variants in a subset of participants recruited with neurodevelopmental disorders in the @genomicsengland.bsky.social National Genomics Research Library, using both precomputed scores, and SpliceAI with updated parameters.
genomicsengland.co.uk
Homepage
Genomics England analyses sequenced genomes for the NHS and then equips researchers to use data to help find the cause of disease.
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Alex Geary @alextremophile.bsky.social · 29/08/2025
Precomputed scores were calculated using a distance parameter of 50nt, however the suggested threshold has increased to 500nt. They can’t handle larger insertions and deletions. And there are errors within the file itself, likely arising from conversion of the original annotations to GRCh38.
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Alex Geary @alextremophile.bsky.social · 29/08/2025
Unfortunately these scores have limitations that can reduce their accuracy in certain contexts: For example changes in transcript annotations, altered transcript boundaries, absence of annotated genes, and changes to exon composition can mean that scores are missed or altered.
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Alex Geary @alextremophile.bsky.social · 29/08/2025
These scores also underlie spliceAI annotations in many variant effect predictors such as the @ensembl.org VEP, forming the basis for annotation in many diagnostic pipelines.
ensembl.org
Ensembl Variant Effect Predictor (VEP)
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Alex Geary @alextremophile.bsky.social · 29/08/2025
SpliceAI is an invaluable tool to identify splice-altering variants. The provision of precomputed scores for all theoretically possible SNVs, 1 base insertions, and 1-4 base deletions has extended this further, massively reducing the time and cost associated with running spliceAI directly.
spliceailookup.broadinstitute.org
SpliceAI Lookup
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Alex Geary @alextremophile.bsky.social · 29/08/2025
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...
medrxiv.org
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 ...
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alexblakes.bsky.social @alexblakes.bsky.social · 18/08/2025
I learned so much from this work and I hope that and discoveries like this can make a real difference to the lives of people living with #RareConditions. Please do share! 😊 www.medrxiv.org/content/10.1...
medrxiv.org
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) ...
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alexblakes.bsky.social @alexblakes.bsky.social · 18/08/2025
The headlines? 1) Variants on both copies of #RNU4-2 cause a recessive neurodevelopmental disorder with prominent speech delay 2) One of the hallmarks is distinct white matter changes on MRI 3) It is clinically and genetically distinct from #ReNU syndrome www.medrxiv.org/content/10.1...
medrxiv.org
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) ...
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Alex Geary @alextremophile.bsky.social · 18/08/2025
An awesome piece of work by @alexblakes.bsky.social, @rociorius.bsky.social, @nickywhiffin.bsky.social and team! I am super excited to see more emerging from this tiny, but mighty gene, and am overjoyed at the implications this has for the rare disorders community ❤️
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Nechama Wieder @nechamawieder.bsky.social · 04/07/2025
3/ The review outlines how UTR variants cause disease, such as: - Create or remove upstream AUGs (uAUGs) - Alter splicing - Alter polyadenylation - Interfere with miRNA or protein binding
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Alex Geary @alextremophile.bsky.social · 04/07/2025
This is such an awesome review paper from @nechamawieder.bsky.social! UTRs are more than just 'buffers' for the coding sequence - they contain a wealth of important regulatory features!
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William Shakespeare @shakespeare.lol · 25/04/2025
You seem’d of late to make the law a tyrant
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Alex Geary @alextremophile.bsky.social · 25/04/2025
Want a Friday mood boost whilst also raising awareness of rare disorders? Then this fresh drop from the band of one of the GEL participant panel members is for you! ♥️🎶♥️ Play it loud, share it widely! (Beware - it is _extremely_ catchy!) open.spotify.com/album/1f2CAX...
open.spotify.com
The A The C The G The T
The Rayne · Single · 2025 · 2 songs
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Dr Zoë Ayres @zjayres.bsky.social · 16/04/2025
Love to my trans sisters, always. #TransRightsAreHumanRights
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the Mountain Goats @themountaingoats.bsky.social · 16/04/2025
if you are a cis person it costs you nothing to just say today that you see & hear your trans sisters & brothers & others over in the UK today -- and around the world, too, knowing that rulings like today's ripple out in ugly ways.
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Alex Geary @alextremophile.bsky.social · 14/04/2025
Finally, and most importantly - this would not have been possible without the support, and contributions made by all the participants and families enrolled in @genomicsengland.bsky.social, their clinical teams, and the staff at Genomics England - to whom we are eternally grateful.
media.tenor.com
a white puppy is laying on the ground with the words `` thank you thank you thank you thank you '' written above it .
ALT: a white puppy is laying on the ground with the words `` thank you thank you thank you thank you '' written above it .
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Alex Geary @alextremophile.bsky.social · 14/04/2025
I would like to give my heartfelt thanks to everyone who has contributed to this work, in particular the incredible @nickywhiffin.bsky.social, Alex Blakes, @drjennylord.bsky.social , Sid Banka and Scott Findlay, who have worked very hard to get this out.
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Alex Geary @alextremophile.bsky.social · 14/04/2025
The take 🏡 : Variants that occur outside of protein-coding regions represent a modest but appreciable contribution to rare disease, and should be routinely incorporated into diagnostic pipelines. (We present a systematic framework for doing this!)
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Alex Geary @alextremophile.bsky.social · 14/04/2025
Looking at the burden that these variants may represent in rare disease we did see an appreciable increase in variants with the potential to disrupt regulation in cases vs controls, though this did not meet the threshold for significance. link.springer.com/article/10.1...
Two panels showing the odds ratios of burden testing results for cases vs controls across regions and annotation types. It shows an increased number of variants  in case vs control participants, however this is modest, and for the KOZAK and 3' intron groups the odds ratios are wide.
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Alex Geary @alextremophile.bsky.social · 14/04/2025
After clinical review, 10 were selected that likely contribute to the participant’s phenotype, 6 of which are confirmed diagnoses. (huge thanks to Alex Blakes, Sid Banka and @drjennylord.bsky.social here! ) link.springer.com/article/10.1...
Figure with four panels, each showing the likely mechanism of disease for the four novel diagnostic variants in this paper. Panel A shows the gene SLC2A1 with a red striped bar representing an upstream open reading from that overlaps the grey striped box (the canonical coding sequence) and extends a short distance into the 5' UTR. Panel B shows the sequence of the NIPBL gene immediately prior to the CDS start site. A red A shows the introduction of an A, forming an AG dinucleotide in the AG exclusion zone, shortly after the predicted splice branch point which is shown in blue. Panel C shows methylation analysis for the SETD5 gene in positive controls (shown in green) and negative controls (shown in purple). The two individuals with the same SETD5 identified in this study are shown as overlapping black dots in the centre of the green positive control group. Panel D shows a sashimi plot of the RNA product for the individual with the GNAS variant (black) and two controls (purple). Higher numbers in the middle block (44 vs 7 and 6) indicate retention of this intron in the affected individual vs controls.
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Alex Geary @alextremophile.bsky.social · 14/04/2025
We identified eleven de novo variants with the potential to disrupt regulatory processes, one of which also appeared in an additional participant, but had not been flagged as a de novo variant.
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Alex Geary @alextremophile.bsky.social · 14/04/2025
Looking at the genomes of 8,040 participants from @genomicsengland.bsky.social’s 100k genomes project, we systematically identified de novo variants that likely disrupt regulatory processes. link.springer.com/article/10.1...
Image with two panels. One shows a schematic of the annotation pipeline used in the analysis, with de novo variant counts at each stage, and within each annotation group, resulting in a final set of 10 variants. 
The second shows the 10 variants highlighted in panel 1 with reference to their genes and annotations. One gold promoter region variant in gene ZBTB18 in the PhyloP annotation group, a star indicates that this was a novel diagnosis in this analysis. One dark red 5' UTR exon region variant in gene SLC40A1 in the PhyloP annotation group, the gene name for this gene is greyed out, indicating it having been excluded from the set of good diagnostic candidates. Two dark red 5' UTR exotic region variants in MEF2C (bold for known diagnosis) and SLC2A1, which is starred to show a new diagnosis. Three 5' Intronic variants in the spliceAI group are shown in teal, two are in the gene PAX6 (bold for known diagnoses) and one in NIPBL which is starred to indicate a novel diagnosis. Two 5' Intronic variants in the spliceAI plus CADD group is shown in teal, one is in RPL26 (bold for known diagnoses) and one in SETD5 which is starred to indicate a novel diagnosis. One 3' Intronic variant in the spliceAI group is shown in teal, this variant is in the gene GNAS and is starred to indicate a novel diagnosis. The final variant is in the 3'UTR exon group with a spliceAI annotation, in the gene MFRP, the gene name is greyed out to indicate it having been excluded as a good diagnostic candidate.
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Alex Geary @alextremophile.bsky.social · 14/04/2025
Individuals with rare conditions often face long diagnostic odysseys, despite advancements in sequencing technologies. We wanted to know if we could find new diagnoses by looking beyond the usual protein-coding candidates, incorporating promoters, and UTRs into a diagnostic framework.
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Alex Geary @alextremophile.bsky.social · 14/04/2025
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 🧵):
link.springer.com
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...
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Greg Findlay @gregfindlay.bsky.social · 11/04/2025
We're quite excited about this story as it showcases the power of SGE to dissect non-coding genes and to uncover new disease associations and diagnoses. This has, indeed, been an excellent collaboration...
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Nicky Whiffin @nickywhiffin.bsky.social · 11/04/2025
🚨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 🧬🖥️🩺 🧵1/12
medrxiv.org
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...
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Alex Geary @alextremophile.bsky.social · 10/04/2025
This is excruciatingly painful to read, and also a really powerful reminder that the participants are always the heart of any study ♥️
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Alex Geary @alextremophile.bsky.social · 02/03/2025
Super late to rare disease weekend, but how awesome is this lady! A stellar scientist, advocate for the rare disease community, mentor, & person. As a rare human, I’m so glad that people like Nicky are doing their absolute best for the rare condition community ♥️ @nickywhiffin.bsky.social
Photo of Nicky Whiffin, the principal investigator of the Rare Disease Genomics group at the university of Oxford. She is smiling in front of a lush green hedge, wearing an excellent teal dress.
The caption reads “Nicky Whiffin, whose team at Oxford University discovered ReNU syndrome’
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Alex Geary @alextremophile.bsky.social · 27/02/2025
I had the honour of accompanying the wonderful Yuyang Chen to the Genetic Alliance #rareDiseaseDay2025 reception today. It was fantastic to meet so many incredible people, and hear such powerful stories. Read the anthology “More than you can imagine” here: geneticalliance.org.uk/campaigns-an...
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Alex Geary @alextremophile.bsky.social · 28/11/2024
Non Science post - I tried to book a GP appointment. They now use an online system requiring an online consultation. This includes a bot that suggests some vaguely horrifying possible diagnoses, and many irrelevant questions. I did submit it - many won't. I still don't have an appointment.
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Gabrielle Brewer @gabriellebrewer.bsky.social · 26/11/2024
If you have any questions about working as an editor at Nature Portfolio, please don't hesitate to reach out.
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Elisa Granato @prokaryota.bsky.social · 26/11/2024
Failure is a cornerstone of scientific research, but it still feels bad. Here is a short article I wrote on how to mentally deal with "failed" experiments. Does a truly "failed" experiment actually exist?? @academic-chatter.bsky.social #academicsky #microsky elisagranato.com/phd-tips-dea...
elisagranato.com
PhD Tips – Dealing with “failed” experiments - Elisa Granato
PhD Tips - Dealing with "failed" experiments "PhD Tips" is a series of articles aimed at graduate students at the University of Oxford (Department of Biology). I wrote this in April 2021. [This articl...
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