Thank you @natgenet.nature.com for this nice Research Briefing www.nature.com/articles/s41... on our recent paper reporting live-cell measurements of Sox2 promoter bursting kinetics when varying its genomic distance from the SCR enhancer 👉 www.nature.com/articles/s41...

The genomic position of an enhancer modulates bursting dynamics of the cognate promoter - Nature Genetics

We show that, in a genomic locus with minimal complexity, the distance between promoter and enhancer modulates the frequency of clustered transcriptional bursts. Thus, besides the nucleotide sequence,...

nature.com

Jian Ma, et al. generated multiscale view connecting genome structure, gene expression, & tissue organization in #Alzheimers. They linked alterations in genome folding to disrupted gene regulation, providing a new layer of insight into biology of #Neurodegeneration. 👉 www.science.org/doi/10.1126/...

Single-cell multiomics connects 3D genome and transcriptome alterations in Alzheimer’s disease

Alzheimer’s disease (AD) disrupts brain function through cell type–specific transcriptomic and epigenomic alterations, yet the contribution of three-dimensional (3D) genome organization to AD remains ...

science.org

Admirable clarity @science.org

David Roberts@volts.wtf · 2w ago

Whew, the editors of @science.org are getting real.

"Hence our dismal conclusion: rather than finding that LLMs free us to do a better job of what we were doing before they came along, they shift scientific incentives (and the playing field of academic competition) in ways that compel us to do more and more, faster and faster, less and less well."

Carl T. Bergstrom@carlbergstrom.com · 2w ago

1. We—@eduede.bsky.social, @mjcrockett.bsky.social, Kevin Gross, and I—have a new preprint on the arXiv today, based on ideas that emerged during an @sfiscience.bsky.social workshop in November 2024: The unintended consequences of large language models as a labor-augmenting technology in science.

Directed evolution of compact synthetic promoters via AlphaGenome and genetic algorithms [new] ...by integrating virtual assay & GFM-guided evolution, iteratively optimizing promoter selectivity, off-target activ., & sequence length.

Adding experimental data made RNA structure predictions worse. Not because the chemistry was wrong. Because the signal alignment upstream was noisy. That is the problem segSHAPE was built to fix. www.biorxiv.org/content/10.6... #Trinobia #ComputationalBiology

segSHAPE: RNA secondary structure prediction from nanopore direct RNA sequencing

RNAs adopt complex structures that regulate key biological processes, making accurate structure prediction essential. Chemical probing coupled with Nanopore direct RNA sequencing (DRS) offers a route ...

biorxiv.org

How can a splicing factor bind to thousands of exons but regulate only a few of them? In our new preprint, we show that SRSF6 resolves this paradox through two distinct binding modes. @lab-nmr.bsky.social & @julianvonehr.bsky.social. Check it out: www.researchsquare.com/article/rs-9...

A new Science study shows that bumble bees can position a ball underneath a fake “flower” to reach a reward, suggesting they can exhibit spontaneous problem-solving and challenging the notion that such advanced cognitive abilities are exclusive to large-brained vertebrates. https://scim.ag/4vs08dC

Code and pipeline are open source: github.com/czbiohub-sf/comparison-RNAVelo Paper: journals.plos.org/ploscompbiol... Need help with your single-cell workflows? trinobia.com/contact/ #RNAvelocity #scRNAseq #Bioinformatics #SingleCell #ComputationalBiology

GitHub - czbiohub-sf/comparison-RNAVelo: Comparison of single-cell RNA Velocity methods in developmental contexts

Comparison of single-cell RNA Velocity methods in developmental contexts - czbiohub-sf/comparison-RNAVelo

github.com

New paper! How do RNAs "know" where to go inside a cell? We dug into the sequence elements that route RNAs to the right place. It turns out that, in mammals, they're surprisingly massive (>200 nt), multipartite, and wonderfully complicated. 🧵

Folddisco is now published @natbiotech.nature.com. It’s a fast motif search for similar 3D DISCOntinuous residues like catalytic sites or zinc fingers across the entire protein universe. 📄 www.nature.com/articles/s41... 💾 folddisco.foldseek.com​​​​​​​​​​​​​​​​ 🌐 https://search.foldseek.com/folddisco

Structural motif search across the protein universe with Folddisco - Nature Biotechnology

Folddisco enables protein structural motif search in million scale databases.

nature.com

Martin Steinegger 🇺🇦@martinsteinegger.bsky.social · last yr.

Folddisco finds similar (dis)continuous 3D motifs in large protein structure databases. Its efficient index enables fast uncharacterized active site annotation, protein conformational state analysis and PPI interface comparison. 1/9🧶🧬 📄 www.biorxiv.org/content/10.1... 🌐 search.foldseek.com/folddisco

What fraction of the human genome is essential for cellular viability? More precisely, how much of the genome is DISPENSABLE for the growth of a haploid cell line? Somewhere between 50 and 96% (nb. as expected). www.biorxiv.org/content/10.6...

Exciting breakthrough technology from the lab, now live in @cellcellpress.bsky.social ! Instead of cutting the genome where proteins bind (e.g., Cut&Tag), D&D-seq scars the DNA with a deaminase, allowing single cell genome mapping of TFs and chromatin remodellers!

Between 1985--2023, MIT's faculty grew 9%. Administrative staff grew 189%. 📈 Why? In new @pnas.org paper, we use dynamical system model to show administrative bloat can emerge without empire-building--just from well-intentioned problem-solving gone awry www.pnas.org/doi/10.1073/...

Large-scale transcriptomic data across four mammalian species and multiple tissues identify conserved molecular signatures associated with ageing and mortality risk. The integration across species, tissues, perturbations, and interventions is a notable strength.

The ZMBH welcomes Dr. James Sáenz @jamessaenz.bsky.social as new Professor in Molecular Biology. James previously led a research group at B CUBE - Center for Molecular Bioengineering of Dresden University of Technology.

Beautiful short Nature Methods N&V “Teaching an old dog new cells” led by J Linder & D Kelley. Also on scooby, pushing seq2func models toward true cell-state–specific reg modeling 🧬 Fitting disc here at CSHL with Anshul & others on this next frontier www.nature.com/articles/s41...

🔬 New in Bioinformatics Advances: "Refining sequence-to-activity models by increasing model resolution"  Read it here: https://doi.org/10.1093/bioadv/vbag122 Authors include: @jbuenrostro.bsky.social, @saramostafavi.bsky.social, @lxsasse.bsky.social

"(...) plasmids are chromatinized in an organized, sequence-dependent manner and adopt a heterogeneous and incomplete chromatin architecture relative to nuclear-encoded chromatin fibers" www.cell.com/molecular-ce...

Chromatin architectures underlying plasmid-based assays for regulatory variant effects

Mallory et al. develop plasmid Fiber-seq to map chromatin architecture along individual transfected plasmids at near-nucleotide resolution, which reveals that plasmids adopt heterogeneous chromatin pa...

cell.com

Game over, phylogeneticists! New DNA foundation model "Carbon" reconstructs the tree of life. 🙃 huggingface.co/spaces/Huggi...

A Review in Communications Medicine explores Long COVID — which affects more than 400 million people globally — including current knowledge, gaps and future directions for research, diagnosis and treatment. go.nature.com/4unyxtI #medsky 🧪

🚨 New preprint! How does noncoding variation drive complex traits? We built a massive atlas of cattle regulatory variants (>150k emVars!) and directly tested them in both bovine AND human cells. 🐄🧬🚶‍♂️ Read it here: www.biorxiv.org/content/10.6...

Why do guinea pigs have so many natural bypass arteries — and mice and humans almost none? We develop in vivo Perturb-seq for endothelial cells to ask how protective collateral arteries are built. Preprint with by Irene Fan, Ronghao Zhou, and Kristy Red-Horse: www.biorxiv.org/content/10.6...

For 40 years the 8-nt ‘Kozak Sequence’ was thought to mark sites of translation initiation. In a new study, we revise this model by identifying an ~80-nt sequence—the extended Translation Initiation Sequence (eTIS)— that guides ribosomes to correct start sites. 🧵 www.biorxiv.org/content/10.6...

Huge congrats from our whole lab to Sir David Attenborough on his 100th birthday!!! 🎉🥳❤️ I had the honor of meeting him - and being interviewed by him - in 2013 for his BBC documentary "Rise of Animals: Triumph of the Vertebrates", which featured part of our work.

Excited to share our new study on CpG islands (CGIs) regulation by transcription factors (TFs)! CGIs drive most transcription initiation with unclear regulation. We find that chromatin-opening TFs are key players—following a surprisingly simple rule. 🧵 www.biorxiv.org/content/10.6... 1/9

Delighted to share our lab's latest (w/ inimitable @genophoria.bsky.social) in final form at @nature.com. Enormous lift by Sean Wang, @palindromephd.bsky.social & @martyyang.bsky.social to address extensive & constructive reviewer comments & see this through. (1/n) www.nature.com/articles/s41...

Pervasive and programmed nucleosome distortion on single chromatin fibres - Nature

An analytical pipeline called Iteratively Defined Lengths of Inaccessibility (IDLI) maps the genome-wide occupancy of a range of nucleosome types and shows that most nucleosomes exhibit programmed ‘di...

nature.com

This a very important, and extremely well-executed study from Ralph Grand’s group @uniheidelberg.bsky.social. Congrats to all the authors! www.biorxiv.org/content/10.6...

Modeling Dynamics, Cell Type Specificity, and Perturbations in Gene Regulatory Networks - www.annualreviews.org/content/jour...

Modeling Dynamics, Cell Type Specificity, and Perturbations in Gene Regulatory Networks

Gene regulatory networks (GRNs) define the regulatory relationships among molecules such as transcription factors, chromatin remodelers, and target genes. GRNs play a critical role in diverse biologic...

annualreviews.org

Very happy to see this review online annualreviews.org/content/journa… where we review current approaches and challenges in GRNs with a focus on dynamics, perturbations and cell type specificity.