Daniel Seaton

An interesting "what have we been doing all these years?" result from this paper is how sub-optimal the widely-used uniform sampling scheme can be (cluster all @50%, sample from all clusters equally). In contrast, strategies that account for the relative differences in cluster size improve val loss

Single task, lightweight, short-context bp res. profile models often perform on par or outperform current large, multi task, long context models on counterfactual prediction. Much to do to improve.

Bonus: robust, efficient interpretation of syntax

Great collab with @jengreitz.bsky.social lab.

📢 new preprint alert: So so excited to share our analysis on the impact of common and rare variants on single-cell gene expression in blood, using WGS and scRNA-seq data from nearly 2,000 individuals and 5.4m cells as part of TenK10K phase 1 🧬 www.medrxiv.org/content/10.1...
🧵👇 (1/n)

Are you a postgraduate student interested in protein modelling and drug discovery?

We have an exciting opportunity to join our team at GSK for a 6-9 months internship, working on an ambitious cross-department research project. Apply before March 14th!

www.linkedin.com/jobs/view/41...

Origins and Implications of Intron Retention Quantitative Trait Loci in Human Tissues Intron retention is a type of alternative splicing in which introns remain unspliced in mature RNA transcripts. In order to explore the landscape and consequences of genetically regulated intron reten...

Very cool paper from Eddie Park and Yi Xing studying the relationship between intron retention QTLs and expression QTLs. Predictably, genetically regulated intron retention can cause changes in gene expression via nonsense-mediated decay (NMD). www.biorxiv.org/content/10.1...

I think the regulatory model (looping etc) first is good with examples that are less extreme and unusual than fto or limb/shh. I think hmgcr and cholesterol is a proximal regulatory effect.

Our ChromBPNet preprint out!

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

Huge congrats to Anusri! This was quite a slog (for both of us) but we r very proud of this one! It is a long read but worth it IMHO. Methods r in the supp. materials. Bluetorial coming soon below 1/

Specificity, length, and luck: How genes are prioritized by rare and common variant association studies Standard genome-wide association studies (GWAS) and rare variant burden tests are essential tools for identifying trait-relevant genes. Although these methods are conceptually similar, we show by anal...

What do GWAS and rare variant burden tests discover, and why?

Do these studies find the most IMPORTANT genes? If not, how DO they rank genes?

Here we present a surprising result: these studies actually test for SPECIFICITY! A 🧵on what this means... (🧪🧬)

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

We are the Stegle Lab: A bioinformatics group advancing computational methods to study molecular variations and their impact on phenotypes. We are jointly hosted at the German Cancer Research Center (@dkfz.bsky.social) and the European Molecular Biology Laboratory (@embl.org) in Heidelberg, Germany.

Characterizing the genetic architecture of drug response using gene-context interaction methods Sadowski et al. propose a framework to study the genetics of response to commonly prescribed drugs in large biobanks. They quantify the heritability of response to statins, metformin, warfarin, and methotrexate, and identify associated genes. Their analysis also shows the importance of accounting for drug use in genetic risk prediction.

New work by Andy Dahl and Michal Sadowski on using GxE to study genetics of drug response now out in Cell Genomics www.cell.com/cell-genomic...

Paired CRISPR screens to map gene regulation in cis and trans https://www.biorxiv.org/content/10.1101/2024.11.27.625752v1 Recent massively-parallel approaches to decipher gene regulatory circuits have focused on the discov

Paired CRISPR screens to map gene regulation in cis and trans https://www.biorxiv.org/content/10.1101/2024.11.27.625752v1

Cross-tissue isoform switches by human transcription factors suggest a widespread regulatory mechanism https://www.biorxiv.org/content/10.1101/2024.11.28.625692v1 Many human genes, including transcription factor (TF) genes, produce alternative coding isoforms. Al

Cross-tissue isoform switches by human transcription factors suggest a widespread regulatory mechanism https://www.biorxiv.org/content/10.1101/2024.11.28.625692v1

To be clear, we do have plans for scaling, we just kinda expected more than a couple days notice before getting blasted with a million new users a day.
The team is rapidly deploying fixes and new software to adapt. More servers in the mail.

My group's work dissecting the contribution of common variants to rare neurodevelopmental conditions is now out at nature.com/articles/s41..., led by co-first authors Qinqin Huang (not yet on blue sky) and @emiliewigdor.bsky.social . See below for Emilie's tweetorial.

Our impact We provide open data that helps scientists understand life and that informs solutions to real-world problems, such as infectious diseases, climate change and food security.

Not enough bioinformatics in your Bluesky feed? We’ve got you covered. Follow us for our latest news, exciting life science research, updates from our data resources, new tools and training resources.

Haven't heard of EMBL-EBI? Take a look at what we’re working on. www.ebi.ac.uk/about/our-im...

Hey, a question for the genetics community. Does genetic fine-mapping work well? How often does it miss?

We usually find that most fine-mapped variants do not fall within coding or regulatory regions. Is it a limitation of epigenomics or a limitation of fine-mapping? Please share your thoughts!

Schematic overview of the proposed mode of action of the newly discovered REX element. Top: An enhancer can activate a gene at a short distance, but not at at long range. Middle: Presence of (C/T)AATTA motifs within an enhancer enable it to act over long distances. Bottom: Coupling a short-range enhancer to the REX element containing the same motifs turns it into a long-range enhancer.

REX - a mammalian "range extender" element that can turn short-distance enhancers into long-distance enhancers.

New preprint from a collaboration led by Grace Bower and Evgeny Kvon.

doi.org/10.1101/2024...

Yes, and also how it informs selection of training datasets. Selecting English language text for English language comprehension, augmenting image datasets by including rotated versions of the same images for image recognition.

I think it already has some physics (eg covalent bond lengths), just less than you might expect (no force field concept). Similar, llms have some knowledge of language (eg the concept of words), just less than you might expect (no verb/noun concept).

Gene regulatory network inference from CRISPR perturbations in primary CD4+ T cells elucidates the g... bioRxiv - the preprint server for biology, operated by Cold Spring Harbor Laboratory, a research and educational institution

Josh Weinstock @joshweinstock.bsky.social at ASHG on inferring GRN from perturbation data

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

Sad to be missing #ASHG23, but check out the talk by the brilliant Wei Zhou talk on Saturday on our new scalable & efficient method for single-cell eQTL mapping!

This is tremendous news, and the quote that "UK Biobank is the world’s most significant resource for health research" is not an exaggeration. Very happy to see it continue to be sustained, especially as we're doing a workshop tomorrow at #ASHG23 on how to use these data!
www.gov.uk/government/n...

Unfortunately I have to miss #ASHG23 this year, but if you are interested in our group's work, do check out these two posters from Ralf Tambets and Krista Freimann:

Presentations from our group at ASHG next week:

Catalogue of Long Read Tools - over 800 entries!

🧬🖥️

long-read-tools.org/table.html

tidyomics Open organizaion of developers creating tidy-style analysis packages in R/Bioconductor and beyond. Reach out to join. - tidyomics

Abdullah @abdnahid.bsky.social first #Bioconductor package {easylift} is released in Bioc 3.18

Facilitates genomic liftover using existing Bioc tools:

ranges |> easylift("hg38")

Abdullah is one of the group that signed up for #tidyomics open challenges: github.com/tidyomics

Very happy to see that our review on gene regulatory networks is being featured by Nature Reviews Genetics and that it inspired its cover! 🥳
doi.org/10.1038/s415...