David A Knowles

Inferring fungal cis-regulatory networks from genome sequences via unsupervised and interpretable representation learning Abstract. Gene expression patterns are determined to a large extent by transcription factor (TF) binding to noncoding regulatory regions in the genome. How

Alan's elegant work on evolutionary contrastive learning for understanding promoter regulatory logic out in @GeneticsGSA! academic.oup.com/genetics/art... Was really fun having him visit my lab for his sabbatical & work on this. New bucket list item: write a first-author paper as a PI!

If you like larger sample sizes, then do check out our reprocessed and fine mapped cis-eQTLs and cis-sQTLs (leafCutter and MAJIQ!) from the INTERVAL cohort (whole blood, n up to 4,729)!
zenodo.org/records/1795...

These will be on the eQTL Catalogue FTP soon as well.

cc @yosephbarash.bsky.social

Mapping isoforms and regulatory mechanisms from spatial transcriptomics data with SPLISOSM - Nature Biotechnology Differential isoform usage is identified with high statistical power from spatial transcriptomics data.

Excited to see this out www.nature.com/articles/s41...! Nonparametric kernel-based tests for spatially variable isoform usage in spatial transcriptomics. So many interesting examples in the CNS and cancer, we're only scratching the surface!

#MLCB2025 proceedings are up at proceedings.mlr.press/v311/ !

Why we made Affinity free, and how we’ll keep it that way We’ve made Affinity completely free, empowering professional designers with studio-grade creative software, supported by Canva’s sustainable ecosystem.

I'm a longtime fan of Affinity Designer as an affordable Illustrator-killer for figures, and... it's now free?! www.canva.com/newsroom/new...
Highly recommended if you're sick of paying Adobe $. Maybe Canva can buy NPG too and get rid of the OA fees.

I'm always amazed when SciENcv works at all!

Get COA coauthor list for NSF including affiliations from PUBMED Get COA coauthor list for NSF including affiliations from PUBMED - coa.py

Little gist for getting coauthor list from PubMed for NSF COA list. Thanks to coauthors gpt5 and claude. gist.github.com/davidaknowle...

The 21st Century version of corvée work for academics is reviewing papers or grants, writing letters of recommendation, giving public outreach lectures.

Large-scale causal discovery using interventional data sheds light on gene network structure in k562 cells - Nature Communications The authors give a method for learning causal gene networks using Perturb-seq data. In K562 cells, they find a network with small-world and scale-free properties. Analysis shows a relationship between...

@brielin.bsky.social's fantastic work on causal gene network inference from Perturb-seq is published! We estimate total causal effects using guides as instruments, then deconvolve into direct & mediated effects with a directed analog of graphical lasso. Deets: nature.com/articles/s41467-025-64353-7

Anyone else not able to log into dbGaP? Can't tell if it's shutdown-related or just the usual struggles. eRA commons seems fine.

MLCB2025 day 2 kicking off with Jacob Schreiber on DL for interpreting and designing regulatory DNA sequence. youtube.com/@mlcbconf

Back up again now, sorry for the interruption after lunch!

Machine Learning in Computational Biology 2025 YouTube video by Machine Learning in Computational Biology

YouTube link for MLCB2025 is up! Starting in 30 min. www.youtube.com/live/19I7xTh...

MLCB - Schedule The in-person component will be held at the New York Genome Center, 101 6th Ave, New York, NY 10013.

#MLCB2025 is tomorrow & Thursday with a fantastic lineup of keynotes & contributed talks www.mlcb.org/schedule. We'll be livestreaming through our YouTube channel www.youtube.com/@mlcbconf. Thanks to www.corteva.com, instadeep.com, the Simons Center at CSHL & NYGC for generous support!

Shiny new probabilistic model, gruyere 🧀, for powering up rare variant associations w/ DL effect prediction! We find novel associations for Alzheimer's disease, e.g. nuclear pore protein NUP93 in microglia. Big thanks to NIH/NIA/ADSP and Anjali for the hard work! authors.elsevier.com/a/1ldzwgeXDzHj

That is one hell of a recruitment photo!

Cas13d-mediated isoform-specific RNA knockdown with a unified computational and experimental toolbox - Nature Communications The majority of human genes can produce multiple isoforms, but studying their functional relevance requires tools to target specific isoforms. Here, the authors develop a CRISPR-based exon-exon juncti...

Excited for this to be out officially! It was a great team effort and has a lot of useful tidbits for studying isoform function. www.nature.com/articles/s41...

Good question. Certainly trickier - you could assume independence across splicing events (quantified via SR) within in a gene and see how well that matches what you get from LR for a matched sample.

Perplexity as a Metric for Isoform Diversity in the Human Transcriptome Long-read sequencing (LRS) has revealed a far greater diversity of RNA isoforms than earlier technologies, increasing the critical need to determine which, and how many, isoforms per gene are biologic...

New work from the lab trying to wrap our heads around the massive complexity of the human transcriptome revealed by long-read RNA-seq! Fun collab with Gloria Sheynkman. www.biorxiv.org/content/10.1...

We had a bunch of requests so we're extending the #MLCB2025 deadline to June 3rd (anywhere on earth)! cmt3.research.microsoft.com/MLCB2025 to submit.

Machine Learning in Computational Biology Youtube channel for the Machine Learning in Computational Biology conference.

Just under a week until the #MLCB2025 paper/abstract deadline on June 1st! In-person registration is full but you can join the wait list forms.gle/gnj6AAV7oWj6... or watch online at youtube.com/@mlcbconf. Sept 10-11 at @nygenome.org. Full deets at mlcb.org! Please RP.

Machine Learning in Computational Biology Youtube channel for the Machine Learning in Computational Biology conference: https://mlcb.github.io/

Free in-person registration is open for #MLCB2025! Sept 10-11 at @nygenome.org and online at youtube.com/@mlcbconf. Paper/abstract deadline is June 1, more deets including our fantastic invited speaker lineup at mlcb.org! Please RP.

Genome-wide mapping of mesoscale neuronal RNA organization and condensation Subcellular RNA organization can affect critical cellular functions. However, our understanding of RNA microenvironments, particularly biomolecular condensates, remains limited, largely due to a lack ...

What drives cytoplasmic mRNA organization? We created unbiased, genome-wide maps of mesoscale RNA-RNA spatial proximity, revealing impact of encoded protein function. Fantastic work from @lindsayabecker.bsky.social @sofiquinodoz.bsky.social @davidaknowles.bsky.social www.biorxiv.org/content/10.1...

Dire wolf cosplay.

Did you know that science labs work like small business entrepreneurs? Faculty hired on strength of ideas, get some startup $ to last 3-4 yrs. After that is grants- grants pay all our + our trainees’ salaries + scientific work. Funding in this country is frozen. That means scientific work stops

Wow. "NIH" canceled my co-mentored (with Dave Sulzer) PhD student's F31 funding. His work is on understanding the genetics and neuroscience of language learning disorders. F31 provides no indirect $ to Columbia, just pays his salary. Not that it should matter, but he's an American citizen. W.T.F.

Just anti funding any science, completely different!

NIH cuts billions of dollars in biomedical funding, effective immediately The move halts a large slice of money for most universities and research institutions virtually overnight, imperiling vital research in everything from cancer to heart disease.

This is dangerously irresponsible on every level. Indiscriminately slashing this funding will cripple lifesaving research on everything from cancer to opioid addiction.

Thinking back on all this I better understand the pain I feel to see science under devastating attack here. It’s not just about my livelihood or my university. It’s about my identity. And it’s about a pursuit that I see as standing along with art, literature, and music as among our highest callings.

An Intuitive Primer on Effective Functional Genomics Study Design Amazon.com: An Intuitive Primer on Effective Functional Genomics Study Design: 9798218585952: Gilad, Yoav: Books

@ygilad.bsky.social has what looks like a useful book just released:
An Intuitive Primer on Effective Functional Genomics Study Design
www.amazon.com/Intuitive-Pr...

I just bought a copy for the lab.