Elzo de Wit lab @ NKI

Elzo de Wit lab @ NKI

@dewitlab.bsky.social

Computational & Genomics Lab studying 3D genome function and dynamics @ Netherlands Cancer Institute

763 followers301 following113 posts

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(1/10) The majority of human genetic variation is located in non-coding regions. The great challenge of the post-genomic era is to assign function to these variants. We reasoned that combining haplotyping with allele-specific multiomics can help pinpoint the functional ones: rdcu.be/fgr5W. A thread:

rdcu.beMapping functional non-coding variation in individual human genomes through haplotyping, multiomics, and deep learningNature Communications - How non-coding mutations in DNA contribute to phenotypes is a largely unresolved question. Here the authors integrate personal genomics and machine learning to identify...

Elzo de Wit lab @ NKI reposted

Ever wanted to watch chromosomes fold? lefsim simulates loop extrusion live in your browser. Add, remove and drag CTCF sites around, watch contact maps emerge, and more. Underneath is a blazing fast Rust engine with Python and JS packages, for research-scale use. Try it: lefsim.abdenlab.org

Elzo de Wit lab @ NKI reposted

Elzo de Wit lab @ NKI reposted

Come join #teamstembryo! We’ll be hiring this round. If you’re broadly interested in the metabolic regulation of mammalian body plan formation, metabolo-mechanics, stem-cell-based embryo models, developmental trajectories… Apply!!

The call for our PhD program is still open until October 20th! Apply now: dipp.cmcb.tu-dresden.de/ausschreibun... We are looking forward to your application!

Elzo de Wit lab @ NKI reposted

🚨 Job Alert - Please share 🙏 Interested in 3D gene regulation in development & evolution? 🤓🧬 💥 Our lab @cabd-upo-csic.bsky.social is expanding! ✅ 4 years fully funded PhD position 🧪 Experimental backgrounds welcome 👇 Details below #PhDPosition #PhDOpportunity #AcademicJobs

Elzo de Wit lab @ NKI reposted

Elzo de Wit lab @ NKI reposted

Elzo de Wit lab @ NKI reposted

Elzo de Wit lab @ NKI reposted

Everything you wanted to know about single-molecule epigenomics but were too afraid to ask! Wonderful to co-write (h/t ENORMOUS lift by @arnaudkr.bsky.social) this primer on our nascent field. Also, a 💯 example of wonderful colleagues building something *together*, not in competition =)

nature.comA practical guide to studying genome function using single-molecule genomicsNature Reviews Molecular Cell Biology - Single-molecule genomics methods are used to study the activity of regulatory factors on individual DNA molecules genome-wide, thereby enabling...

Elzo de Wit lab @ NKI reposted

Reposting this ongoing search (any discipline of biology) for an Assistant to Associate level colleague in the Division of Basic Sciences at Fred Hutch. Great city, great colleagues, great core facilities, great trainees.

Harmit Singh Malik@harmitmalik.bsky.social

Come be our colleague. I have been in this Division for 27 years (4 as a postdoc and 23 as a PI). It is an amazing place to work, collaborate, and be inspired. If you are applying to be an Assistant or Associate Professor this Fall, don't miss this deadline.

Elzo de Wit lab @ NKI reposted

Elzo de Wit lab @ NKI reposted

Elzo de Wit lab @ NKI reposted

And finally—a bit of personal news: 🔬 I’m on the faculty job market this year! I’m looking for tenure-track opportunities where I can build a lab at the intersection of developmental biology, mechanobiology, reproductive biology & aging.

Kate Cavanaugh@katecavanaugh.bsky.social

🧵 What if one reason fertility declines with age isn’t just genetic-but mechanical? Thrilled to share our new paper in @NatureCellBio : Elevated contractility drives implantation failure in mouse embryos from aged females… here’s what we found 👇 www.nature.com/articles/s41... 1/11

Elzo de Wit lab @ NKI reposted

How do nuclear compartments form inside cell nuclei? We show RNA glues certain loci together to form a nuclear compartment. This involves special GC-rich regions of highly expressed genes that also associate with nuclear speckles, but interactions between these loci are independent of speckles!

bioRxiv Genomics@biorxiv-genomic.bsky.social

Formation of an RNA-mediated nuclear compartment https://www.biorxiv.org/content/10.64898/2026.08.20.746005v1

Elzo de Wit lab @ NKI reposted

Remember this? bsky.app/profile/did:... Rigorous visualization of the structure in your high-dimensional data. Fantastic work by @dhdegroot.bsky.social With help of the reviewers of Nat Biotech it is now updated, extended an officially published here: www.nature.com/articles/s41... 1/n

nature.comBonsai reconstructs tree representations for distortion-free visualization and exploration of high-dimensional data - Nature BiotechnologyHigh-dimensional data are visualized through representation on tree structures.
Erik van Nimwegen@erikvannimwegen.bsky.social

Here it is! Bonsai. Now there is really no more excuse for using t-SNE/UMAP. Bonsai not only makes cool pictures of your data. It actually rigorously preserves its structure. No tunable parameters. Incredible work by @dhdegroot.bsky.social. I'm so excited about this! www.biorxiv.org/content/10.1...

Elzo de Wit lab @ NKI reposted

🚨 Job Alert - Please share 🙏 Interested in 3D gene regulation in development & evolution? 🤓🧬 💥 Our lab at @cabd-upo-csic.bsky.social is expanding! ✅ 4 years fully funded PhD position 💻🧪 Experimental or computational backgrounds welcome 👇 Details below #PhDPosition #PhDOpportunity #AcademicJobs

Elzo de Wit lab @ NKI reposted

Sign up now for the EMBO meeting 'quantitative biology to molecular mechanisms'. Fantastic speaker lineup and plenty of speakers slots selected from abstracts. Submit your abstract before Sept 11!

EMBL Events@events.embl.org

You only have until 11 Sep to submit your abstract for #EMBOomics! ➡️ s.embl.org/omx26-01-bl Join us to discuss the latest developments in the field with leaders in genomics, dynamic proteomics, quantitative imaging, and synthetic biology.

Elzo de Wit lab @ NKI reposted

Come be our colleague. I have been in this Division for 27 years (4 as a postdoc and 23 as a PI). It is an amazing place to work, collaborate, and be inspired. If you are applying to be an Assistant or Associate Professor this Fall, don't miss this deadline.

Fred Hutch Basic Sciences Division@basicsci.fredhutch.org

Join @FredHutch.org's Basic Sciences Division as an Assistant or Associate Professor and help shape the future of fundamental biology. We welcome applicants whose work will complement, extend, or bring new directions to the division.

Elzo de Wit lab @ NKI reposted

We are looking to hire a technician to join the team. This project focuses on the nuclear lamina, a cellular structure that protects and organizes the genome. Will build skills in genetic screening, genomics, and stem cell culture. Please share, please apply! aprecruit.ucsf.edu/JPF06185

aprecruit.ucsf.eduJunior Specialist, Buchwalter Laboratory, Cardiovascular Research InstituteUniversity of California, San Francisco is hiring. Apply now!

Elzo de Wit lab @ NKI reposted

Elzo de Wit lab @ NKI reposted

We are looking for someone to lead the new Facility for Protein Biochemistry & Biophysics at the MPI of Immunobiology and Epigenetics in Freiburg — please spread the word and apply if you are interested!

🚀 Job alert: We’re starting a new Facility – and you can lead it! The MPI-IE & @mariekeoudelaar.bsky.social are hiring a Head of Protein Biochemistry & Biophysics to launch and lead a brand-new Core Facility in Freiburg 🇩🇪. Once-in-lifetime-chance. Details ⬇️ jobs.ie-freiburg.mpg.de/jobposting/b...

(1/10) The majority of human genetic variation is located in non-coding regions. The great challenge of the post-genomic era is to assign function to these variants. We reasoned that combining haplotyping with allele-specific multiomics can help pinpoint the functional ones: rdcu.be/fgr5W. A thread:

rdcu.beMapping functional non-coding variation in individual human genomes through haplotyping, multiomics, and deep learningNature Communications - How non-coding mutations in DNA contribute to phenotypes is a largely unresolved question. Here the authors integrate personal genomics and machine learning to identify...
View full thread

(1/10) The majority of human genetic variation is located in non-coding regions. The great challenge of the post-genomic era is to assign function to these variants. We reasoned that combining haplotyping with allele-specific multiomics can help pinpoint the functional ones: rdcu.be/fgr5W. A thread:

rdcu.beMapping functional non-coding variation in individual human genomes through haplotyping, multiomics, and deep learningNature Communications - How non-coding mutations in DNA contribute to phenotypes is a largely unresolved question. Here the authors integrate personal genomics and machine learning to identify...
View full thread

(8/10) With our analyses, we discovered a rare variant that disrupts OCT motif within a distal enhancer of PIK3R5 gene. Using CRISPR-Cas9 variant editing we restored PIK3R5 gene activity, validating predictions and showing variant causality for its expression.

(1/10) The majority of human genetic variation is located in non-coding regions. The great challenge of the post-genomic era is to assign function to these variants. We reasoned that combining haplotyping with allele-specific multiomics can help pinpoint the functional ones: rdcu.be/fgr5W. A thread:

rdcu.beMapping functional non-coding variation in individual human genomes through haplotyping, multiomics, and deep learningNature Communications - How non-coding mutations in DNA contribute to phenotypes is a largely unresolved question. Here the authors integrate personal genomics and machine learning to identify...
View full thread

(6/10) To this end, we used ChromBPNet deep learning models to learn TF motif syntax. We then searched for variants that disrupt TF binding sites thus explaining allele-specific accessibility. This revealed hundreds of TF binding disruptions, which we validated using ChIP-seq data.

(7/10) Looking at the genes we linked to these variants, a number of known and several putative causal variants were picked up, including their likely mechanisms of action through TF motif disruption. And all of this achieved using data from single individuals instead of large cohorts!

(1/10) The majority of human genetic variation is located in non-coding regions. The great challenge of the post-genomic era is to assign function to these variants. We reasoned that combining haplotyping with allele-specific multiomics can help pinpoint the functional ones: rdcu.be/fgr5W. A thread:

rdcu.beMapping functional non-coding variation in individual human genomes through haplotyping, multiomics, and deep learningNature Communications - How non-coding mutations in DNA contribute to phenotypes is a largely unresolved question. Here the authors integrate personal genomics and machine learning to identify...
View full thread

(4/10) The identified regulatory links showed a high degree of concordance between accessibility and expression, particularly at shorter distances, and were consistent with eQTL associations from the population-based data.

(5/10) These results suggest that we can detect functionally relevant variant-gene links using data from only a single individual. But how do we move from correlation to causality and find the mechanisms by which variants drive allele-specific gene regulation?

(1/10) The majority of human genetic variation is located in non-coding regions. The great challenge of the post-genomic era is to assign function to these variants. We reasoned that combining haplotyping with allele-specific multiomics can help pinpoint the functional ones: rdcu.be/fgr5W. A thread:

rdcu.beMapping functional non-coding variation in individual human genomes through haplotyping, multiomics, and deep learningNature Communications - How non-coding mutations in DNA contribute to phenotypes is a largely unresolved question. Here the authors integrate personal genomics and machine learning to identify...

(2/10) To link regulatory variants to gene expression across large distances, we reconstructed chromosome-scale haplotypes using 10X linked-reads and Hi-C. This enabled high-quality phasing of variants in five individuals with diverse genetic backgrounds.

(3/10) Next, we mapped chromatin accessibility and gene expression via ATAC-seq and TT-seq. Integrating these with phased variants, we built a personal-genome pipeline to quantify and connect allele-specific open chromatin peaks to genes.

Elzo de Wit lab @ NKI reposted