Simone Zaccaria

UCL – University College London UCL is consistently ranked as one of the top ten universities in the world (QS World University Rankings 2010-2022) and is No.2 in the UK for research power (Research Excellence Framework 2021).

🚨 We're hiring a sequencing technician in #TRACERx!
Join world-leading teams at @TheCrick & @uclcancer, working at the forefront of cancer research.
Want to apply cutting-edge genomic tech to understand cancer evolution? Apply now!

👉 www.ucl.ac.uk/work-at-ucl/...

#Genomics #CancerResearch

Computational Cancer Genomics (CCG) Research Group We are the Computational Cancer Genomics (CCG) Lab at the UCL Cancer Institute, a group of passionate scientists and clinicians who work on developing computational methods to unravel cancer's mysteri...

1 in 2 people will get cancer in their lifetime. Our team'll still run @cancerresearchuk.org Muddy Race also this May to highlight the importance of funding cancer research and improving patient outcomes

Please support us if you can! #RaceforLife
👉 fundraise.cancerresearchuk.org/team/computa...

Not only are you a brilliant PI and an incredible mother, but you’re also a role model for women in science. Your strength and dedication inspire us all!

I'm participating the ISMB/ECCB 2025 conference, join me! Register now

I'm attending #ISMBECCB2025 in Liverpool, United Kingdom from July 20-24. Who else is going? Register here and don't miss it! invt.io/1bxbyktm0wq

Huge congratulations to now PhD @alexsteinresearch.bsky.social and supervisor @benjaminwerner.bsky.social , well deserved! It has been a pleasure to listening to and discussing such a great amount of work and how it all came together

Manuscript logo, phylogenetic tree of mouse strains with different but highly reproducible patterns of cancer evolution. Demonstrated by rerunning cancer evolution in a controlled system.

To what extent is cancer development deterministic and predictable..?

Does the germline genome affect that predictability...?

Preprint: www.biorxiv.org/content/10.1...

A big moment for our Centre - the first algorithm to identify cells responsible for aggressive tumour growth.

SPRINTER can measure proliferation of distinct clones within the same tumour, using DNA sequencing data. This could facilitate better prediction of cancer progression, informing treatment.

Tumor Evolution Reconstruction Is Heavily Influenced by Algorithmic and Experimental Choices Tumor progression is an evolutionary process during which cells acquire distinct genetic alterations. Several cancer evolutionary studies reconstruct this evolutionary process by applying bulk DNA seq...

How much do algorithmic and experimental choices drive the accuracy of reconstructing tumour evolution?

In this Cancer Research commentary, @zaccasimo.bsky.social and I discuss a recent Nature Biotech benchmarking paper exploring this question:

bit.ly/3VAMRQs

🚨 Very proud of this commentary led by @rijazaidi.bsky.social reasoning on the impact of methods and experimental design on cancer evolution understanding, motivated by the outstanding work of @TheBoutros, @VanLooLab, @kellrott et al

Original work 👉 doi.org/10.1038/s415...

Our Commentary 👇

Reposting this list of #cancer #evolution scientists, in case its useful for the many newcomers.

So proud that our paper introducing SPRINTER to characterise clone proliferation through cancer evolution is out in Nature Genetics!

Twenty-seven scientists become EMBO Young Investigators – Press releases – EMBO The group leaders join an international network of nearly 800 life scientists and receive financial support

🎉 Hugely honoured & happy to be selected for the
@embopress.org EMBO Young Investigator Programme 2024!

Exciting opportunity for our group @ccg-ucl.bsky.social & grateful for the support of @uclofficial.bsky.social @uclnews.bsky.social & funders @cancerresearchuk.org

www.embo.org/press-releas...

We are so grateful to @qianxidu.bsky.social for this outstanding News&Views piece highlighting our recent SPRINTER work and framing it so beautifully within the literature. A truly valuable resource! 🙏

Read it here: 👉 doi.org/10.1038/s415...

🧵 Dive into SPRINTER's work: 👉 bsky.app/profile/zacc...

Luminal breast epithelial cells of BRCA1 or BRCA2 mutation carriers and noncarriers harbor common breast cancer copy number alterations - Nature Genetics Single-cell DNA sequencing identifies recurrent copy number changes in healthy breast tissue from women with wild-type or germline BRCA1 or BRCA2 mutations.

Our paper on chromosomal abnormalities in normal breast tissue from BRCA carriers came out last week.
www.nature.com/articles/s41...

What an absolute pleasure to be collaborating with such an incredibly talented team!!

SPRINTER out today in Nature Genetics 🧬

A great pleasure to work with @zaccasimo.bsky.social and his team on this elegant data and tool.

Thank you, Trevor!

Thank you, Wei! 😊

Characterizing the evolutionary dynamics of cancer proliferation in single-cell clones with SPRINTER - Nature Genetics Single-cell Proliferation Rate Inference in Non-homogeneous Tumors through Evolutionary Routes (SPRINTER) allows users to infer proliferation rates of individual clones within a tumor from single-cell...

Single cell genomics was a breakthrough in understanding cancer heterogeneity. Incredible work by Lucas et al. in breaking the next barrier, cancer proliferation heterogeneity tinyurl.com/mjuuk7kt

Honoured I was invited to write the News&Views. tinyurl.com/yc27a4ac

Both out now in Nature Genetics!

All of this was really only possible thanks to the support of our funders @cancerresearchuk.org also inc @RosetreesT @bcrfcure.bsky.social @wellcometrust.bsky.social , our teams @uclofficial.bsky.social @thecrick.bsky.social @CRUKLungCentre, and the patients & participants #TRACERx #PEACEautopsy

This is also the first step and output of my @cancerresearchuk.org Career Development Fellowship, and you can read its overall vision and goal in a recent
@cancerresearchuk.org 's blog post 👇

news.cancerresearchuk.org/2024/02/27/u...

This was led by stellar @ojlucas.bsky.social and wouldn't have been possible without @charlesswanton.bsky.social @NnennayaKanu cosupervision, @sophie-ward.bsky.social key collaboration, @rijazaidi.bsky.social @abibunkum.bsky.social key contributions and help of many others inc. Mariam and Nicky

📰Read full story 👉 rdcu.be/d1S6m

🖥️SPRINTER is fully available in GitHub 👉 github.com/zaccaria-lab...

🚆Distributed through Bioconda (with also related container) 👉 bioconda.github.io/recipes/spri...

💾also with a reproducible capsule in CodeOcean👉 doi.org/10.24433/CO.... pic.x.com/zpL2rhbRhl

Finally, we proved SPRINTER’s broad applicability on prev datasets of 61,914 TNBC and HGSC cells and found other key insights for high prolif clones:
❗️Increased single-cell rates of genomic variants
‼️Enrichment of prolif-related gene amplifications

❔-> Evolutionary advantage?

When integrating serial ctDNA samples across 4 timepoints, we found differential ctDNA shedding between clones, with high prolif clones shedding more ctDNA

🚨It shows that previous similar observations obtained across different tumors also hold for distinct clones within a tumor

What's their role? We reconstructed met dissemination patterns and found that:
1. high prolif clones seeded most mets disseminating from other mets
2. met-seeding clones had high proliferation

❔-> association between high prolif and met seeding potential of individual clones

Maybe non-genetic? Leveraging SPRINTER, we developed an approach to identify clone-specific altered replication timing (ART)

‼️ We found ART unique to the high prolif and metastatic clones affecting key genes like KRAS, and with associated expression changes from matched RNA-seq

To find potential causes of these proliferation differences, we performed a detailed phylogenetic analysis of both SNVs and CNAs, as SPRINTER now enables the simultaneous analysis of clones' evolution and their proliferation.

⛔️ No clearly associated genetic driver was found

SPRINTER revealed widespread proliferation heterogeneity both in primary tumor and mets, and both between and within samples. We validated these with orthogonal analyses, including Ki-67 staining, nuclei imaging and clinical imaging.

❓-> Yes, clones can proliferate differently

To answer the initial questions ❓ and ❔, we generated a unique scDNA, longitudinal, primary-metastasis-matched dataset of 14,994 non-small cell lung cancer cells from a patient enrolled in the #TRACERx and #PEACEautopsy studies, and we applied SPRINTER to it