ksamocha.bsky.social
Kaitlin Samocha
@ksamocha.bsky.social
1.5K followers 230 following 58 posts
Assistant Investigator @ MGH / Broad / HMS. Focus on human genomics and modeling rare variation. She/her
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Reposted by Kaitlin Samocha
pragskore.bsky.social
Pragati Kore @pragskore.bsky.social · 2d
📃 We’re excited to share our latest work, now published in Nature Communications — a major update to the Genome Aggregation Database (gnomAD) that improves allele frequency resolution for two gnomAD-defined genetic ancestry groups using local ancestry inference (LAI).
Improved allele frequencies in gnomAD through local ancestry inference - Nature Communications
This study incorporates local ancestry into the Genome Aggregation Database (gnomAD) to improve allele frequency estimates for admixed populations, enhancing variant interpretation and enabling more accurate and equitable genomic research and clinical care.
www.nature.com
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Reposted by Kaitlin Samocha
mattneville.bsky.social
Matthew Neville @mattneville.bsky.social · 18h
Now published! Our paper on:
(1) Accurate sequencing of sperm at scale
(2) Positive selection of spermatogenesis driver mutations across the exome
(3) Offspring disease risks from male reproductive aging
[1/n]
www.nature.com/articles/s41...
Sperm sequencing reveals extensive positive selection in the male germline - Nature
A combination of whole-genome NanoSeq with deep whole-exome and targeted NanoSeq is used to accurately characterize mutation rates and genes under positive selection in sperm cells.
www.nature.com
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Reposted by Kaitlin Samocha
nickywhiffin.bsky.social
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 👇

🧵 1/4
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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Reposted by Kaitlin Samocha
nickywhiffin.bsky.social
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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Reposted by Kaitlin Samocha
jamesfasham.bsky.social
James Fasham @jamesfasham.bsky.social · May 24
🗣️ Quote of #ESHG2025 (so far)

"Who licks bone !?!" 🦴
- Johannes Krause

Anyone have that on your bingo card?

Well apparently archeologists do, to distinguish bone from stones and it causes problems in DNA sequencing. 🤔
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ksamocha.bsky.social
Kaitlin Samocha @ksamocha.bsky.social · May 24
We are just wrapping up day 1 at #ESGH2025 in beautiful Milan. For those who want some extra fun while listening to the great science, you can play bingo.👇

I know multiple of these have already occurred.
ahoischen.bsky.social
Alex Hoischen @ahoischen.bsky.social · May 23
Getting ready for #eshg2025 …and our postdoc @lydiasagath.bsky.social made a nice BINGO card again.
Paying a lot of attention to the entire event will pay off!
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Reposted by Kaitlin Samocha
ahoischen.bsky.social
Alex Hoischen @ahoischen.bsky.social · May 24
Buongiorno Milano! Ready for a great day 1 of #eshg2025?
Packed program of excellent science 8.30am-8.00pm - plus networking event till 9.30pm to meet many friends, colleagues and collaborators! …andiamo @eshg.bsky.social @eshgyoung.bsky.social
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Reposted by Kaitlin Samocha
zornitza.bsky.social
Zornitza Stark @zornitza.bsky.social · May 23
🤗 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!
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...
www.medrxiv.org
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Reposted by Kaitlin Samocha
deciphergenomics.bsky.social
deciphergenomics.bsky.social @deciphergenomics.bsky.social · May 7
Human Developmental Cell Atlas (HDCA) expression data is now displayed. Expression is displayed in 12 sections of a 6-7 post-conception week human embryo, alongside a sagittal view which displays the region of the embryo represented by each section @mhaniffa.bsky.social
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Reposted by Kaitlin Samocha
nickywhiffin.bsky.social
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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ksamocha.bsky.social
Kaitlin Samocha @ksamocha.bsky.social · Feb 21
Yes, I've done this once before for a paper (listing in the system only first and last authors). It is easy to get those handful of people to approve additional authors in the future if the journal requires it.

Not sure if recommended, but it saved time.
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Reposted by Kaitlin Samocha
eventswcs.bsky.social
Wellcome Connecting Science Learning and Training @eventswcs.bsky.social · Feb 17
Join leading experts working in #RareDisease research at our #GRD25 conference.

📅 Dates: 9-11 April 2025
💭 Share insights in person

Explore the latest #genomics advances accelerating improvements in clinical care for rare disorders, globally.

⏰Secure your place by 11 March: bit.ly/3BpAe44
Genomics of Rare Disease (hybrid conference) Dates: 9-11 April 2025 Location: Hinxton Hall Conference Centre, Wellcome Genome Campus, UK and online In-person registration deadline: 11 March 2025 Virtual registration deadline: 1 April 2025
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ksamocha.bsky.social
Kaitlin Samocha @ksamocha.bsky.social · Apr 19
Projects like this can’t be completed without many others: thanks to Mark Daly for continued mentorship across the years; critical support and work from @anneotation.bsky.social, @konradjk.bsky.social, Predrag Radivojac; the Hail team; and everyone associated with @gnomad-project.bsky.social.

10/10
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ksamocha.bsky.social
Kaitlin Samocha @ksamocha.bsky.social · Apr 19
If this work feels familiar, it is because it is building off older work from our team originally released for ExAC.

I view this iteration as more of a franchise reboot instead of a sequel – we have new leads, but similar themes.

9/10
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ksamocha.bsky.social
Kaitlin Samocha @ksamocha.bsky.social · Apr 19
As with all gnomAD-led projects, we’ve already shared the data and code. Regions are displayed for v2 on the gnomAD browser, the code can be seen on Github (github.com/broadinstitu...), and MPC scores are available for download.

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ksamocha.bsky.social
Kaitlin Samocha @ksamocha.bsky.social · Apr 19
There is still much more to learn: using 125k exomes, our median region size is ~450bp and we see a relationship between transcript length and the number of regions we can identify due to statistical power.

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ksamocha.bsky.social
Kaitlin Samocha @ksamocha.bsky.social · Apr 19
Finally, missense constraint information was incorporated into a deleteriousness metric named MPC (Missense deleteriousness Prediction by Constraint), which separates case from control de novo missense variants well with similar performance to ML models like AlphaMissense.

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ksamocha.bsky.social
Kaitlin Samocha @ksamocha.bsky.social · Apr 19
In collaboration with Predrag Radivojac and team, we demonstrated that coding bases with < 20% of their expected missense variation achieve moderate support for pathogenicity (PM1) following ACMG/AMP guidelines that can be used for clinical classification.

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ksamocha.bsky.social
Kaitlin Samocha @ksamocha.bsky.social · Apr 19
Missense depleted regions show an enrichment of (1) de novo missense variants in neurodevelopmental disorder cases compared to controls, (2) partitioned common variant heritability for >260 independent traits from the UK Biobank, and (3) ClinVar pathogenic (P/LP) variants.

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ksamocha.bsky.social
Kaitlin Samocha @ksamocha.bsky.social · Apr 19
Why try to find subgenic regions that are specifically missense constrained? Splitting up genes reveals patterns of negative and neutral selection that are obscured when looking gene-wide, including highlighting regions that have a large number of known pathogenic variants.

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ksamocha.bsky.social
Kaitlin Samocha @ksamocha.bsky.social · Apr 19
Co-led by the fabulous Katherine Chao and Lily Wang, we used gnomAD v2 and a recursive search to identify ~28% of canonical transcripts that were split into multiple missense constraint regions (measured by variable missense depletion in gnomAD).

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ksamocha.bsky.social
Kaitlin Samocha @ksamocha.bsky.social · Apr 19
Recently out on #bioRxiv: our updated approach to identify regional variability in missense mutation intolerance (“constraint”) in protein-coding genes using the gnomAD database.

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

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ksamocha.bsky.social
Kaitlin Samocha @ksamocha.bsky.social · Mar 8
Some updated guidance on our gnomAD v4 constraint scores: gnomad.broadinstitute.org/news/2024-03...

The @gnomad-project.bsky.social team is hard at work on v4.1 and improvements across the board, so expect more updates.

Thanks to Katherine Chao for spearheading this blogpost.
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ksamocha.bsky.social
Kaitlin Samocha @ksamocha.bsky.social · Dec 8
A freely accessible version of the paper can be found here: rdcu.be/dsVXx
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ksamocha.bsky.social
Kaitlin Samocha @ksamocha.bsky.social · Dec 8
Our data are freely available on the gnomAD browser (gnomad.broadinstitute.org).

A huge thank you to Mike Guo, Laurent Francioli, Sarah Stenton, and Julia Goodrich for their hard work on this. This, of course, wouldn't be possible without everyone involved with @gnomad-project.bsky.social.
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