Leopold Parts

High frequency body site translocation of nosocomial Pseudomonas aeruginosa - Nature Communications Here, the authors report within-host diversity and body site translocation dynamics in hospital samples of Pseudomonas aeruginosa and reveal that body site sharing was likely due to within-patient tra...

Really pleased to share the first paper to come out of the lab.
We found that hospital patients were frequently colonised with P. aeruginosa and that the same clone was shared between the gut and the lung.
The phylogenies indicate that the clones moved from lung->gut

www.nature.com/articles/s41...

New paper “Proteome-wide model for human disease genetics” is now live at Nature Genetics: rdcu.be/eRu7K
popEVE (pop.evemodel.org) finds the needles in the haystacks of human genetic variation:

final week to apply for @sangerinstitute.bsky.social PhD programme (due Nov 27th) -- free to apply, open to anyone anywhere, and a superb training opportunity for students interested in genomic approaches applied to biodiversity, pathogens, vectors, and of course us pesky humans.

Yes, this is where you would work (the round building, not the boat)

We are looking for a postdoc to join our team! If you're interested in translating a cutting edge genomics technology (www.nature.com/articles/s41...) to real-life applications in hematology, this is for you. We offer a unique working environment ON THE BEACH: recruitment.crg.eu/content/jobs...

Our new preprint is online! Viruses, bacteria and parasites use effector proteins to evade immunity and rewire host cell pathways. Together with @AlexanderStark8, we wondered if we could systematically map what these effectors, regardless of their origin, do in human cells. 1/8

Major new direction in the lab: hacking human cell biology with pathogen effectors (eORFs) - amazing collaboration with @miketilapia.bsky.social lab. Huge congrats to first authors Tomas & He & all co-authors! Check out the pre-print on @biorxivpreprint.bsky.social www.biorxiv.org/content/10.1...

Join us and these amazing speakers next March'26 at Synthetic Biology for Health and Sustainability - an international conference held at the Wellcome Genome campus near Cambridge UK.

Abstracts deadline: December 1st, 2025

Register here - x.com/gallowaylabm...

Congratulations @hilarycmartin.bsky.social from @sangerinstitute.bsky.social on being awarded the 2026 Balfour Lecture!

Congratulations to Richard Durbin on being awarded our Genetics Society Medal!

Genotype-level quality control substantially reduces error rates in population-scale whole-genome sequencing Population-scale whole-genome sequencing data will contain many individual-level genotype errors, even after allele-level quality control (QC). We establish the need for genotype-level QC using UK Bio...

New paper on everyone’s favourite topic, QC!
We show why you should do genotype-level QC on your WGS data

www.biorxiv.org/content/10.1...

Very real quotes about this paper -
“The most exciting, mind-blowing paper of the year!”
“On a par with Fisher 1918”
“I read it every night. Just so beautiful”

tinyurl.com/GenGenFaculty

GenGen is hiring group leaders! If you want to generate data at scale to train the next generation of AI models to make molecular biology predictive and programmable, we want to hear from you.

Overall, we showed that paired prime editing can generate ultra-long deletions, and that it can be used to interrogate the genome in a pooled manner - ultimately promising to unlock functional secrets from all the gigabases of our genome.

Our pooled deletion screen was surprisingly efficient, with high replicate reproducibility (R=0.84) and 75% recall of positive controls. Most signal was from deletions in protein-coding genes, but some deletions in regulatory elements near promoters, splice junctions, and 5′UTRs were also depleted.

Then we scaled up. Using improved long oligo synthesis (@twistbioscience.com), we encoded both pegRNAs in a single construct, enabling true pooled paired prime editing. We designed 10,471 deletions across 149 genes using the PE7 system from Britt Adamson's lab.

Precise and ultra-long deletions enable the correction of disease-relevant mutations. For retinitis pigmentosa, we deleted entire exons at up to 84% efficiency, and for Duchenne muscular dystrophy, we could engineer therapeutic 340kb deletions at up to 13% efficiency.

We also wanted to understand the role of 3D proximity of the deletion ends on editing efficiency and measured contact frequency using micro-capture C. There was a strong correlation between proximity and deletion length, but even for deletions >100kb, contact frequency correlates with efficiency.

To understand which deletion features explain the observed editing rates, we build a XGBoost model and identified deletion length, contact frequency, the GC content of the PBS, spacer efficiency (DeepCas9), and pegRNA efficiency (PRIDICT2, Nicolas Mathis and Schwank lab) as key drivers.

We first tested the limits of deletion length for prime editing by screening >3.8k deletions of up to 1.2 Mb in a reporter locus. Efficiency was best for <5 kb deletions, but even megabase-scale ones worked at single-digit rates, to our knowledge, the largest prime-edited deletions ever reported.

We still don’t know what most of the human genome does. To figure that out, we need to delete big stretches of DNA, thousands of times. But classical CRISPR creates toxic double-strand breaks that introduce measurement noise. That’s where paired prime editing comes in.

Generating long deletions across the genome with pooled paired prime editing screens Engineered deletions are a powerful probe for studying genome architecture, function, and regulation. Yet, the lack of effective methods to create them in large numbers and at multi-kilobase scale has...

New 🧬✂️ pre-print! We show that paired prime editing can efficiently generate large deletions — even >1 Mb — with high precision and at scale. We use this to perform the first pooled prime deletion screen across the human genome.

🔗 biorxiv.org/content/10.1...

A short thread (by Juliane Weller)👇

Dr. Leopold Parts initially trained in mathematics and computer science before switching to molecular biology and genomics for his Ph.D., and high-throughput screening for the postdoctoral research. He is currently a group leader at the Wellcome Sanger Institute, where his team aims to understand human DNA function in its cellular context. To do so, they currently focus on generating data from cell lines whose genomes carry many large-scale systematic changes compared to the reference. His team has created several tools and datasets to probe the editing efficacies of CRISPR/Cas systems, as well as applied them to map the extent of variation in gene phenotypes between individuals.

The "High-Content CRISPR Screening" conference will take place on March 18-19, 2026, in Vienna, Austria. Don’t forget to register and submit an abstract!

Conference website: perturb2026.bio

Meet the Speaker: @leopoldparts.bsky.social

TF-MAPS: fast high-resolution functional and allosteric mapping of DNA-binding proteins Transcription factors (TFs) bind specific DNA sequences to control gene expression. Modulating TF activity is of considerable therapeutic interest but very few TFs have been successfully drugged. TF D...

TF-MAPS: fast high-resolution functional and allosteric mapping of DNA-binding proteins by @XianghuaLi2

Are Transcription Factors really 'undruggable'?

www.biorxiv.org/content/10.1...

Please RP! A 4-day synbio and tissue engineering conference #MASSIV to transform biology and medicine together.

Couldn't list all amazing speakers, so please check out this 👉https://www.massivconference.com/

Poster due is Nov 7, but will be extended.

With @stemcellnetwork.ca and JST.

Announcing the new “Functional Genomics and Systems Biology” section in GENETICS The GSA Journals are introducing Functional Genomics and Systems Biology, a new section led by Brenda Andrews and Marian Walhout that highlights systems-level studies of genetic networks and pathways.

🎉 New in #GENETICS: Functional Genomics & Systems Biology section! Highlighting cutting-edge studies on molecular networks, systems-level insights, and innovative methods.

Read more: buff.ly/wWVZdrS%F0%9...

Celebrating the first 1000 genomes of Lepidoptera in Europe, sequenced at @sangerinstitute.bsky.social in collaboration with sampling hubs across the UK via the DToL project www.darwintreeoflife.org & across Europe via
@projectpsyche.bsky.social www.projectpsyche.org &
@10klepgenomes.bsky.social

GitHub - allydunham/dnacomb: CLI tool for flexibly parsing structured sequence reads into count tables and comparing them to expected libraries CLI tool for flexibly parsing structured sequence reads into count tables and comparing them to expected libraries - allydunham/dnacomb

We've been screening across many DNA construct structures with variable number/size of interesting regions - e.g. spacer, extension and barcode for prime editing. There wasn't a widely used tool to process these complex structured reads so I ended up developing github.com/allydunham/d....

Somatic mutation and selection at population scale - Nature A new version of nanorate DNA&nbsp;sequencing, with an&nbsp;error rate&nbsp;lower than five errors&nbsp;per billion base pairs&nbsp;and compatible with whole-exome and targeted capture, enables epidemiological-scale studies of somatic mutation and selection&nbsp;and&nbsp;the generation of high-resolution&nbsp;selection&nbsp;maps across coding and non-coding sites for many genes.

Our latest work is out in Nature today. In this paper, we introduce an improved version of NanoSeq, a duplex sequencing protocol with <5 errors per billion bp in single DNA molecules, and use it to study the somatic mutation landscape of oral epithelium in >1000 people www.nature.com/articles/s41...

Happy to share that this work together with @opentargets.org is now out at Nature Communications.

Group Leader – AI in Biology Are you ready to lead groundbreaking research in AI for Biology? Join us at EMBL! We are seeking a visionary scientist to establish their own independent research group bridging innovations in machine...

Are you an AI expert who wants to stay in academia and change the world by understanding the most complex things we know - living organisms? Want to lead your own group, based in Heidelberg DE, working language English? @embl.org is hiring in AI embl.wd103.myworkdayjobs.com/en-US/EMBL/j...

Genomics continues to revolutionise science.

But there’s untapped potential for new discoveries through collaboration between genomics and the humanities, social sciences, bioethics and wider stakeholders.