David A Knowles

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.

It's been very helpful around NYGC in Soho, no more stationary honking cars trying to squeeze into the Holland tunnel.

It's been 3 weeks since Congestion Relief Zone tolling went into effect, and the program is working!

We're seeing traffic move quicker into and within Manhattan, which benefits all New Yorkers—drivers, bus riders, emergency vehicle operators, pedestrians, and more.

#MLCB2025 will be Sept 10-11 at @nygenome.org in NYC! Paper deadline June 1st & in-person registration will open in May. Please sign up for our mailing list groups.google.com/g/mlcb/ for future announcements. More details at mlcb.github.io. Please RP!

Cellular behavior analysis from live-cell imaging of TCR T cell–cancer cell interactions T cell therapies, such as chimeric antigen receptor (CAR) T cells and T cell receptor (TCR) T cells, are a growing class of anti-cancer treatments. However, expansion to novel indications and beyond l...

First post in the Good Place! Our preprint on cellular behavior analysis in TCR T cells & cancer cell live-cell imaging data is out! This 3-year collaboration led by pd Archit Verma w/ Alex Marson & Julia Carnevale, with segmentation & tracking by @davidvv & team! www.biorxiv.org/content/10.1...

Who will protect our environment from Trump?

Non-profit environmental lawyers. They won hundreds of cases against Trump 45 and have been hiring new lawyers for months. They are ready for this moment.
Follow and donate to:
@earthjustice.bsky.social @nrdc.org @centerforbiodiv.bsky.social

Reviewing is getting ridiculous. On 7th Jan I agreed to review a manuscript. I just got an email telling me my review was due on 2nd Jan. Adding time travel to the skill set expected of junior faculty.

Just explain Bayesian credible intervals instead!

Probabilistic Modeling in Genomics Cold Spring Harbor Laboratory Meetings & Courses -- a private, non-profit institution with research programs in cancer, neuroscience, plant biology, genomics, bioinformatics.

There are 10 days left to submit abstracts to ProbGen meetings.cshl.edu/meetings.asp...! Fantastic line-up of speakers and topics.

Error with enumeration for hierarchy of GLMs Hi all. I have a model which is a hierarchy of GLMs where I want to test a null vs full model for each sub-GLM (there are params shared between these GLMs in the real version although not in the MWE b...

Do any pyro aficionados have insight on what I'm doing wrong here? forum.pyro.ai/t/error-with...

python/torch, all fp32. it's a floating point (and order of operation) issue, so could happen in any language.

Curious if any of the LLMs would have spotted this as a potential gotcha.

After ~2h of bug hunting: needed to replace lgamma(a+n-y) with lgamma(n-y+a). For tiny a and n=y>0, the former evaluates to +inf and breaks everything, the latter doesn't. 🫠

Gotta love that the only way to give feedback on the reporting burden of NIH's data management & sharing plan template is by 🐌 mail.

Most of the talks from our Oct meeting are now online, with a few more to come: www.precisionmedicine.columbia.edu/videos

Within-Family GWAS does not Ameliorate the Decline in Prediction Accuracy across Populations As polygenic prediction extends beyond the research domain to involve clinical applications, the urgency of solving the “portability problem” becomes amplified—that is, the fact that polygenic indices...

A surprising (to me) result! Polygenic score portability across groups does not improve if based on within-family GWAS, which accounts for most forms of environmental confounding. Suggests genetic architecture is main driver and shows within-family GWAS aren't a solution to poor PGS transferability.

Our new (social media) era at @plos.org has officially started - this is the first @plosbiology.org research paper to be posted on Bluesky and *not* on X. Give it some love!