Advances in CLIP-derived methods have enabled high-resolution mapping of individual RNA binding protein-RNA interactions as well as RNA binding protein-associated RNA–RNA interactions #RNA #CLIP @evannostrandlab.bsky.social bit.ly/4bYjAsg

One on left is a black dog and above it the words “Reality”. Below it is “I chased a squirrel” One the right is a black dog and above it says “LinkedIn”. Below it says, Proud to announce that I effectively executed a rapid-response squirrel displacement strategy to mitigate potential yard intrusions. Humbled by the unwavering support of my family and local stakeholders. This experience reinforced the importance of vigilance, ownership, and continuous improvement. Looking forward to scaling this impact in future engagements.

😂

You typically give condolence speeches with slides ? 😉

Mechanisms linking cytoplasmic decay of translation-defective mRNA to transcriptional adaptation Transcriptional adaptation (TA) is a genetic robustness mechanism through which mutant messenger RNA (mRNA) decay induces sequence-dependent up-regulation of so-called adapting genes. How cytoplasmica...

Ever notice that when one gene is disrupted, its orthologs get upregulated? This phenomenon, known as transcriptional adaptation, has been controversial and mysterious - glad to see that we are starting to learn how it works.

Clever use of proteomic data to stress-test TWAS and QTL colocalization methods, revealing a high false sign rate. This hypothesis about high-LD and cross-tissue confounding is particularly interesting:

Does the noncoding genome actually carry more genetic information than coding seqs? Motivated by this question we mutated every bp in the 10kb MYC locus. Results are even more exciting: Decoding the MYC locus reveals a druggable ultraconserved RNA element www.biorxiv.org/content/10.6...

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

Embracing Uncertainty in Life, Science

It has been a long time since I wrote a non strictly scientific blog post. The holiday time, often a time of reflection and new resolutions, seems good for getting back to that. But don’t worry, there will be connections to science work as well… 😉 Today’s…

Announcing the 2026 edition of the EMBO workshop on RNA localization and local translation! This meeting will be held June 30 - July 4 near Porto, Portugal. Come for exciting updates in the field from both established investigators and trainees. See the link below for details!

@rnasociety.bsky.social now offers an "undergraduate" category for membership! rnasociety.memberclicks.net/membership #RNA@PUI

Enabling Discovery Through Genomics (EDGE)

The new Enabling Discovery through GEnomics (EDGE) Program page is posted. Please contact us at BIOEDGE@nsf.gov if you have questions. www.nsf.gov/funding/oppo...

The U.S. Is Funding Fewer Grants in Every Area of Science and Medicine (Gift Article) A quiet policy change means the government is making fewer bets on long-term science.

New York Times article on science funding with some depressing but familiar curves with interactive graphics.

www.nytimes.com/interactive/...

Finally, we have new models, more results and more analysis brewing in all those areas so stay tuned! 😀

#3 David Wang led MAJIQTL method development with validations by Peter Choi lab (CHOP/UPenn) and joint students Kevin Yang and Benjamin Wales-McGrath. This project started many years ago with the late and great Casey Brown to whom we dedicated this work 💔

#2: Matthew Gazzara led the APA/DDX55 paper, a joint effort with co-mentor Kristen Lynch

#1 Farica Zhuang led G4mer with Danielle Gutman performing validations, Dan Dominguez lab (UNC) structure validation and Kate Nathanson (UPenn) helped with the Breast cancer analysis.

As I noted, each paper is a different comp approach, and a different element of RNA processing! I just find this so exciting we can do this kind of science in the lab 🙂 This is possible because (a) lab members did terrific job 👏💪(b) great collaborators 🙌😊. Specifically:

A Deep Dive into sQTL Modeling – Part 2 In my previous post, I described how, in our recent sQTL preprint, we broke current sQTL pipelines into their basic elements. This led to identifying potential issues/areas we may be able to improv…

we published blog posts that give an overview of what's new here: biociphers.wordpress.com/2025/01/20/a... biociphers.wordpress.com/2025/01/28/a...

A nice write up about this work just came out on #alzforum www.alzforum.org/news/researc... and also

Co-localization of sQTLs and AD and PD GWAS variants increased by 64% and 92% respectively compared to current standard, and we experimentally test an sQTL associated with exon 7 in MS4A3 co-localized with AD that disrupts the RBP YBX3 binding site by blocking that region with ASO.

A deep dive into statistical modeling of RNA splicing QTLs reveals variants that explain neurodegenerative disease Current methods for detecting splicing quantitative trait loci (sQTLs) miss many disease-associated genetic variants. MAJIQTL introduces improved statistical modeling and comprehensive splicing repres...

#3: Last but not least, we released a new method for splicing #QTL which uses #MAJIQ under the hood but then adds new statistical modeling. The new MAJIQTL results in major power increase (can be > 2 fold in some cases) with improved control over false positives. www.cell.com/ajhg/fulltex...

We identify a new role for DDX55 as APA regulator with an associated mechanism where it can unwind local structure to either hide APA signals or bring those to be in the “right” distance - cool beans! 😎🫘

Integrative analysis of RNA binding proteins identifies DDX55 as a novel regulator of 3’UTR isoform diversity - Genome Biology Background The 3’ untranslated regions (3’UTRs) of mRNAs play a critical role in controlling gene expression and function because they contain binding sites for microRNAs and RNA binding proteins (RBP...

#2: We performed a large scale analysis of alternative polyadenylation ( #APA ) changes after RNA Binding Protein (RBP) Knockdown (KD). The entire APA quantifications across ENCODE is given as a resource you can use but we focus on DDX55. genomebiology.biomedcentral.com/articles/10....

Negative selection, effect of mutations...subtypes matter! We validate effect on effect on structure and downstream gene translation of Breast cancer associated variants that either create or disrupt rG4. Transcriptome wide predictions are available for gnomAD as well as online prediction tool

G4mer: An RNA language model for transcriptome-wide identification of G-quadruplexes and disease variants from population-scale genetic data - Nature Communications RNA G-quadruplexes (rG4s) are structures formed in guanine-rich regions of RNA that can serve as crucial regulatory elements in gene expression. Here the authors present an RNA language model for tran...

#1: G4mer is an #LLM to predict #RNA G-Quads (rG4) and their subtypes. www.nature.com/articles/s41.... Yes, it's much more accurate... more interestingly, we show current experimental data used by ML/AI methods is biased to short, canonical, rG4 and that not all rG4 are created equal:

I'll preface, each of these papers represents a different facet of the labs research both in terms of the RNA and the Comp methods, making me very happy and proud about them 😊. So let’s start.. (no particular order)

📣📣📣 (one for each new paper from the lab😀): Within ~1 week we had 3 papers published (two in the same day!), each took years... This calls for a quick tweetorial to explain why these may be interesting for you if you are into #RNA processing ( #Splicing #APA #UTR #rG4) with #AI #StatisticalGenetics.

Really cool paper that changed the way I think about what GWAS and Burden tests are doing, and also basically made me pleiotropy-pilled

Enabling options for review: from training and transparency to author-centered AI tools - openRxiv Peer review is widely viewed as a critical aspect of biomedical communication. Ideally, it provides authors with feedback so they can improve manuscripts and gives readers, particularly nonspecialists...

Excited to launch an openRxiv partnership with the scientist-run AI review service qed (@qedscience.bsky.social), the brainchild of @odedrechavi.bsky.social 1/n

openrxiv.org/enabling-rev...

Choose your human genome reference wisely - Nature Methods Scientists can choose between multiple human genome references, and a pangenome reference is coming. Deciding what to use when is not quite straightforward.

As new human assemblies become available on beta.ensembl.org - which human reference genome will you choose? This article explores the question with insights from Ensembl’s own Fergal Martin - www.nature.com/articles/s41...

#HumanGenomics #Pangenomes #ReferenceGenomes