🧵1/ Excited to share our new paper introducing a new #singlecell assay: scTF-seq, a high-throughput single-cell approach to explore how transcription factor (TF) dose shapes cell identity and reprogramming outcomes. 🔗 www.nature.com/articles/s41... Big congrats to the entire team @EPFL & @SIAT_China

Outstanding Faculty opportunity in the broad area of 'life sciences engineering' @EPFL School of Life Sciences, open to both junior and senior researchers. We may prefer metabolism-centric applications but remain open to outstanding applications across domains: www.epfl.ch/about/workin...

Our new review on how #microfluidics has been key for (#single-cell) #genomics & how it will remain essential to support this new era of single cell #phenomics: www.nature.com/articles/s41.... Great timing for the Microfluidics Gordon Research Conference here in Lucca! www.grc.org/physics-and-...

🚀 study: www.cell.com/cell/fulltex... from @larsplus.bsky.social et al: via enhancer design from scratch, 3 principles emerged: 1) TF binding strength = activation 'or' repression; 2) Same motif ≠ same output in all cell states; 3) 2 activators ≠ activation - combos can repress! #geneRegulation

Impressive, new snRNA-seq atlas across 8 mouse strains & tissues reveals how genetics shapes cell-type-specific gene expression. A key resource for decoding trait variation, disease mechanisms & guiding mouse model design. #Genomics #SingleCell #PrecisionMedicine. www.biorxiv.org/content/10.1...

Amazing 🚀 study w/ DNA seqFISH+, enabling mapping of 100,049 genomic loci, together with the nascent transcriptome for 17,856 genes, yielding unpredented insights into subnuclear structures in single cells www.nature.com/articles/s41...

Great opportunity! 🎆

New tool 💪 from @steinaerts.bsky.social lab: CREsted, a DL-based approach for predicting cell type-specific reg. elements, applying it to many datasets, incl. mouse cortex, human PBMCs & glioblastoma, demonstrating its ability to identify key TF binding sites: www.biorxiv.org/content/10.1...

Science under attack: a growing list of statements from journals @jama.com jamanetwork.com/journals/jam... @plos.org theplosblog.plos.org/2025/02/plos... @science.org www.science.org/doi/10.1126/... @nature.com www.nature.com/articles/d41... @embopress.org www.embopress.org/doi/full/10....

#scRNAseq to the next level: www.biorxiv.org/content/bior.... Mindbogglingly 100M cell large dataset involving 50 cancer cell lines and 1,100 molecule perturbations 🤩 — an absolute feast for the data-hungry ML/AI field, poised to advance cell understanding and modeling.

Really cool method 'Trace-n-seq' that allows for the molecular characterization of single neurons that innervate the pancreas and how this is altered in a cancer context at high resolution. www.nature.com/articles/s41...

wow 🚀! Need to look into the details, but sounds really exciting: Seq-Scope-X --> new spatial transcriptomics & proteomics technology that achieves sub-200 nm super-resolution, surpassing the diffraction limit of optical microscopy by physically enlarging tissues. www.biorxiv.org/content/bior...

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A new mechanism for cancer-induced immune evasion. We knew about cancer cells hijacking mitochondria. Now we learn about how their mitochondrial transfer to T cells impairs the tumor immune response. www.nature.com/articles/s41... www.nature.com/articles/d41...

Interesting study showing how a heart disease-linked TF, TBX5, regulates 3D chromatin independently of transcription, via structural and cohesin-regulating roles in a dose-dependent fashion www.biorxiv.org/content/10.1...

Cool new method (PERFF-seq) for profiling rare cell states via #scRNAseq, allowing for the isolation of rare cell populations by fluorescently labeling specific transcripts after which the respective cells are sorted, thus uncovering more phenotypic heterogeneity. www.nature.com/articles/s41...

Fantastic opportunity: 🚀 Calling early-career scientists! Apply for the 2025 ELISIR Scholar at EPFL. From outstanding PhD straight to group leader. Join an interdisciplinary research community to conduct independent research in any area of #lifesciences in Lausanne, CH 👉 go.epfl.ch/ELISIR

Interesting study showing that Bicoid clusters in fly embryos preserve nuclear concentration info, guiding gene expression despite non-linear LLPS models. These clusters also act as high-fidelity sensors, key for fast, precise transcriptional regulation. www.science.org/doi/10.1126/...

Superb work by Wouter @Zouters & @OlgaPushkarev developing ChromatinHD, two scale-adaptive #machinelearning models & interpretation tools that use #scRNAseq + #scATACseq data to better understand how chromatin accessibility relates to gene expression doi.org/10.1038/s414... Happy 2025 everyone 🎆 !

Cool framework to systematically compare & evaluate methods that integrate scRNA+ATAC-seq data to infer GRNs, highlighting limitations & variability in performance across different tasks and clear challenge to capture causal relationships from perturbation assays www.biorxiv.org/content/bior...

Interesting study on the use of #scRNA-seq data for protein level prediction. It highlights the limitations of mRNA as a predictor of protein expression and the effectiveness of #machine-learning models in improving protein abundance estimations. www.biorxiv.org/content/10.1...

Judith's magnum opus from her postdoc in our lab: a genome-integrated massively parallel reporter assay for quantitative insights into enhancer-promoter communication, AI benchmarking, variant dissection, & promoter motif characterization. It will be the foundation of her new lab @USC, Jan 2025! 🚀

📣 Please share: We’re hiring a tenure-track Group Leader in Multicellular Systems to explore the molecular and cellular mechanisms driving the formation, maintenance, or destabilization of tissues, organs and organisms. Apply at: www.fmi.ch/education-ca...

1/7 Planning to build a single-cell atlas? Or wondering how atlases can be useful to your research? Read our guide on single-cell atlases www.nature.com/articles/s41... published in Nature Methods, by @lisasikkema.bsky.social, @khrovatin.bsky.social, Malte Luecken, @fabiantheis.bsky.social et al.

Major milestone: Tabula Sapiens 2.0 maps tissue composition & TF expression in 175 cell types, identifying 745 ubiquitous & 890 cell type-specific TFs (many still uncharacterized -> #Codebook) w/ roles in tissue homeostasis, stress response & metabolism. #SingleCell www.biorxiv.org/content/10.1...

A grand milestone in single cell drug screening!

A deep learning-based image analysis algorithm, MouseMapper, to enable comprehensive analysis of disease-associated changes at the whole-body scale, and applied to study nervous and immune systems in high-fat diet induced obesity. One word: wow!

Really cool 'synthetic' approach to better understand the molecular mechanisms underlying endogenous (!) gene regulation, something that the field has so far been lacking!

Massive study to identify functional relationships between genes and understand how genetic background influences gene perturbation effects. www.biorxiv.org/content/10.1...

Huge effort resulting in improved TF binding site models. Congrats to the winners but also all participants for pushing analytical borders and finally also to Vanja Kulakovskiy @halfacrocodile.bsky.social‬ & team for organizing it all!

Interesting study showing that the incorporation of Med15 into Gcn4 condensates and the formation of soluble complexes with Med15 are better predictors of transcriptional activity than homotypic phase separation www.biorxiv.org/content/10.1...

Please share broadly! We (Molecular Genetics, University of Toronto) are looking for a new faculty member! Deadline Dec 19. Those working on model organisms and using genomics, computational and systems approaches are strongly encouraged to apply! Reach out w/ Qs! jobs.utoronto.ca/job/Toronto-...

How do cells remember transient signals? New work reveals that a transient pulse of histone deacetylase inhibition leaves a lasting mark on 3D genome architecture in mESCs, linking chromatin dynamics to cellular memory and gene expression robustness. www.biorxiv.org/content/10.1...

I think we all do & those who claim otherwise I don't believe ;). As PIs, it's simply hard to keep up with many rapidly evolving fields at the same time, making us feel superficial. But it's also the beauty of being a scholar: we can learn from our own lab members and colleagues around us!

Amazing 💪

The Institute for Integrative Biology of the Cell #I2BCParisSaclay is seeking to recruit new group leaders in cell biology #UnivParisSaclay #CNRSbiologie #CEAParisSaclay The application dealine is February 28, 2025

Interesting outlook on the anticipated impact of single-molecule temporal omics to track RNA, proteins and metabolites in real-time to capture dynamic molecular heterogeneity doi.org/10.1038/s415...

Really nice new paper using transfer learning with precise TF dose modulation to predict how chromatin accessibility at REs responds to changes in TF levels, also showing how TF dose perturbations can induce distinct phenotypes, even within shared cellular contexts, but lots of questions remain!

This huge effort started >6 yrs ago, using 5 TF-DNA binding assays (ChIP-seq, genomic & conv. HT-SELEX, PBM & SMilE-seq) to probe the uncharacterized TF space, likely reaching the limit of 'human DNA binding capacity'. Great collab. w/ ‪@halfacrocodile.bsky.social‬, @timhughesto.bsky.social & teams

Incredible resource for DNA binding protein specificity from the Codebook consortium. www.biorxiv.org/content/10.1... www.biorxiv.org/content/10.1... www.biorxiv.org/content/10.1... www.biorxiv.org/content/10.1... Am reading these in detail & will have a lot to say. Stay tuned for thoughts.

Excited to contribute a final Codebook paper. Great work by @antonigralak.bsky.social & team using a new methylation-sensitive SMiLE-seq method to explore the methylation-specific DNA binding preferences of (uncharacterized) human #TranscriptionFactors #Epigenetics www.biorxiv.org/content/10.1...

(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 ⬇️.

Very happy w/ our new work, excellently conceived & led by Judith Kribelbauer (new Faculty at USC starting Jan 2025!), uncovering a 'new' TF class: 'context TFs' that boost local enhancer activity and mediate enhancer-enhancer communication, forming ‘chromatin modules’. For details, t.co/Nk6DBD4CGk

👉Great opportunity for those stemming from computer science, physics, engineering, applied mathematics, or other relevant AI fields, aiming e.g. to use their expertise to advance biology/medicine: epfl.ch/research/fun.... Feel free to reach out!