(1/14) Excited to share our new preprint: ArChIPelago — classic ML on top of multiple PWMs improves genomic TFBS prediction. shorturl.at/jnxDA Builds on our MEX paper (Vorontsov et al., 2025). w/ @pensarata.bsky.social @vorontsovie.bsky.social @sevamakeev.bsky.social @halfacrocodile.bsky.social

New paper showing that much of the apparent success of protein language models in predicting mutational effects is a mirage: These models mostly memorize sites. 1/ www.biorxiv.org/content/10.6...

Our team achieved first place in the CAGI7 lentiMPRA challenge on predicting the effects of single-nucleotide mutations in regulatory elements, surpassing the nearest competitors by a significant margin.

(1/13) Excited to share the outcome of the IBIS Challenge! The IBIS challenge united dozens of teams across the world in tackling the problem of modeling transcription factor (TF) binding specificity using a diverse collection of experimental datasets for understudied human TFs.

Excited / nervous to share the “magnum opus” of my postdoc in Andreas Wagner’s lab! "De-novo promoters emerge more readily from random DNA than from genomic DNA" This project is the accumulation of 4 years of work, and lays the foundation for my future group. In short, we… (1/4)

De-novo promoters emerge more readily from random DNA than from genomic DNA

Promoters are DNA sequences that help to initiate transcription. Point mutations can create de-novo promoters, which can consequently transcribe inactive genes or create novel transcripts. We know lit...

biorxiv.org

Out in Cell @cp-cell.bsky.social: Design principles of cell-state-specific enhancers in hematopoiesis 🧬🩸 screen of fully synthetic enhancers in blood progenitors 🤖 AI that creates new cell state specific enhancers 🔍 negative synergies between TFs lead to specificity! www.cell.com/cell/fulltex... 🧵

Design principles of cell-state-specific enhancers in hematopoiesis

Screen of minimalistic enhancers in blood progenitor cells demonstrates widespread dual activator-repressor function of transcription factors (TFs) and enables the model-guided design of cell-state-sp...

cell.com

Finally published! We developed an epigenomics to therapeutics screening approach that identifies naturally occurring elements that can titrate expression of transgenes at various levels including single elements stronger than the B-globin LCR. www.nature.com/articles/s41...

Large-scale discovery of potent, compact and erythroid specific enhancers for gene therapy vectors - Nature Communications

This study presents a large-scale enhancer screening approach to optimize gene therapy vectors. A compact, potent, erythroid-specific enhancer used in a therapeutic vector, improved viral titers, tran...

nature.com

Our preprint on designing and editing cis-regulatory elements using Ledidi is out! Ledidi turns *any* ML model (or set of models) into a designer of edits to DNA sequences that induce desired characteristics. Preprint: www.biorxiv.org/content/10.1... GitHub: github.com/jmschrei/led...

Programmatic design and editing of cis-regulatory elements

The development of modern genome editing tools has enabled researchers to make such edits with high precision but has left unsolved the problem of designing these edits. As a solution, we propose Ledi...

biorxiv.org

We share a lot of our ideas, code, datasets (that we spend years sanitizing) early. Often way before we release preprints. We do this so that others can use, build on, improve & even "beat" our approaches. But I want to say a few things about some simple expectations 1/

We wrote a review article on modelling and design of transcriptional enhancers using sequence-to-function models. From conventional machine learning methods to CNNs and using models as oracles/generative AI for synthetic enhancer design! @natrevbioeng.bsky.social www.nature.com/articles/s44...

Modelling and design of transcriptional enhancers - Nature Reviews Bioengineering

Enhancers are genomic elements critical for regulating gene expression. In this Review, the authors discuss how sequence-to-function models can be used to unravel the rules underlying enhancer activit...

nature.com

Super excited to announce our latest work. On a personal note, it's not an exaggeration to say that blood, sweat, and tears got us to the finish line on this: working w/ an outstanding global team of scientists in Germany, Japan, Russia, and USA responding in >100 pages of complex reviewer comments.

Massively parallel characterization of transcriptional regulatory elements - Nature

Lentivirus-based reporter assays for 680,000 regulatory sequences from three cell lines coupled to machine-learning models lead to insights into the grammar of cis-regulatory elements.

nature.com

Finally out! We present EXTRA-seq, a new EXTended Reporter Assay to quantify endogenous enhancer-promoter communication at kb scale! www.biorxiv.org/content/10.1... A 🧵about what it can do: #SynBio #DeepLearning #GeneRegulation

EXTRA-seq: a genome-integrated extended massively parallel reporter assay to quantify enhancer-promoter communication

Precise control of gene expression is essential for cellular function, but the mechanisms by which enhancers communicate with promoters to coordinate this process are not fully understood. While seque...

biorxiv.org

Wonderful. Just two weeks ago I was explaining to a junior colleague the problem of exaggerated claims in science. This paragraph is exactly what should be printed in place of a user agreement when anybody submits a paper.

Rommie Amaro@rommieamaro.bsky.social · 2y ago

@dereklowe.bsky.social honing in on the same bottom line message from @wpwalters.bsky.social @prof-ajay-jain.bsky.social it's so true and hits so hard:

Join us for our next Kipoi Seminar with with Dmitry Penzar, @pensarata.bsky.social @ autosome.org! 👉LegNet: parameter-efficient modeling of gene regulatory regions using modern convolutional neural network 📅Wed Dec 4, 5:30pm CET 🧬 kipoi.org/seminar/

(1/6) 🐦‍🔥 In IBIS #ibischallenge, we challenged teams from all over the world to decipher the DNA recognition code of human transcription factors. The IBIS Final Conference took place on November 27, 2024. Recordings and slides: disk.yandex.ru/d/82FEnwPn15...

Excited to share our latest preprint on scE2G – a new model to link enhancers to target genes using single-cell data – with state-of-the-art performance across multiple perturbation benchmarks. biorxiv.org/cgi/content/... Read more below! 1/12

Mapping enhancer-gene regulatory interactions from single-cell data

Mapping enhancers and their target genes in specific cell types is crucial for understanding gene regulation and human disease genetics. However, accurately predicting enhancer-gene regulatory interac...

biorxiv.org

Pooled CRISPR screens with joint single-nucleus chromatin accessibility and transcriptome profiling go.nature.com/4hXER5O

Pooled CRISPR screens with joint single-nucleus chromatin accessibility and transcriptome profiling - Nature Biotechnology

MultiPerturb-seq profiles gene expression and chromatin accessibility in single-cell pooled CRISPR screen.

go.nature.com

Really nice overview and systematization of things done in the area. I found a few works in there that I've completely missed

Pooja Kathail@poojakathail.bsky.social · 2y ago

Super excited to share our review on genomic deep learning models for non-coding variant effect prediction, with Ayesha Bajwa and Nilah Ioannidis. We’d like this review to be a useful resource, and welcome any feedback, comments, or questions! 1/4 arxiv.org/abs/2411.11158

New on BioRxiv: We report a new, endogenous molecular clock in unmodified human cells and tissues. It is ticking away right now in almost every cell in your body. Paper here: www.biorxiv.org/content/10.1... 1/

Regulatory plasticity of the human genome https://www.biorxiv.org/content/10.1101/2024.11.13.623439v1

Regulatory plasticity of the human genome https://www.biorxiv.org/content/10.1101/2024.11.13.623439v1

Evolutionary turnover in non-coding regions has driven phenotypic divergence during past speciation

biorxiv.org

(1/8)📢Excited to announce the bioRxiv submission of my work from the past three years! Introducing meSMiLE-seq, a microfluidic assay aimed to understand how DNA modifications impact transcription factor (TF) binding, as part of the large Codebook/GRECO-BIT collab dx.doi.org/10.1101/2024... ✨🧵 ⬇️

They say science and cats should be posted here

(1/4) In IBIS (ibis.autosome.org), we challenged teams from all over the world to decipher the DNA recognition code of human transcription factors. Today, we are excited to announce the Final IBIS Conference scheduled for November 27, 2024.

(1/12) Excited to present the results of the large-scale benchmarking of DNA motif discovery tools using the Codebook data compendium on poorly studied human transcription factors and the Codebook Motif Explorer: dx.doi.org/10.1101/2024..., mex.autosome.org ⬇️.

Regulation of transcription by condensates, great review by @bsabari.bsky.social and coll. www.nature.com/articles/s41...

Transcription regulation by biomolecular condensates - Nature Reviews Molecular Cell Biology

Transcriptional condensates, which are formed through dynamic multivalent interactions between proteins, RNA and chromatin, regulate transcription by compartmentalizing its machinery in the crowded nu...

nature.com

Preprint describing the systematic identification of TF binding motifs and of TFs which preferentially bind methylated DNA. #epigenomics

bioRxiv Genomics@biorxiv-genomic.bsky.social · 2y ago

Identification of methylation-sensitive human transcription factors using meSMiLE-seq https://www.biorxiv.org/content/10.1101/2024.11.11.619598v1

Perspective on recent developments and challenges in regulatory and systems genomics arxiv.org/abs/2411.04363 Great perspective piece from an all-star author list on the current state of regulatory genomics and the challenges ahead.

Perspective on recent developments and challenges in regulatory and systems genomics

Predicting how genetic variation affects phenotypic outcomes at the organismal, cellular, and molecular levels requires deciphering the cis-regulatory code, the sequence rules by which non-coding regi...

arxiv.org