Yuri Pritykin

Using Gloss, we’ve uncovered molecular programs underlying myeloid-T cell interactions in cancer immunotherapy and T cell-T cell interactions during viral infection.

Hope Gloss is useful for your own LIPSTIC + scRNA-seq!
It is efficient, interpretable and even generalizable to CITE-seq.

Universal recording of immune cell interactions in vivo - Nature A paper reports the development of a universal tool for studying cellular interactions in biological systems, and demonstrates its coupling with single-cell transcriptomics methods to provide insights...

Gloss uses overlapping group lasso regression to systematically link gene and pathway activity to LIPSTIC-measured interaction intensities.

It is applicable to both uLIPSTIC (doi.org/10.1038/s415...) and 1st generation LIPSTIC (doi.org/10.1038/natu..., doi.org/10.1126/scii...)

Happy to present Gloss, our new computational method for the analysis of multi-modal LIPSTIC + scRNA-seq data coupling cell-cell interaction measurements with intracellular transcriptomes.

Paper: doi.org/10.1016/j.cr...

Led by an amazing PhD student Tamjeed Azad, with @victora.bsky.social

Predictive modeling of molecular activity underlying physical cell-cell interactions Azad et al. introduce Gloss, a computational framework that links intracellular gene programs measured with scRNA-seq to physical cell-cell interactions measured by LIPSTIC. Using a group lasso approach, Gloss robustly identifies the molecular drivers of immune communication in models of cancer and viral infection.

Predictive modeling of molecular activity underlying physical cell-cell interactions

Benchmarking cell type deconvolution in spatial transcriptomics and application to cancer immunotherapy https://www.biorxiv.org/content/10.64898/2026.01.13.699379v1

Thrilled to announce a new PhD from the lab, Dr. Sarah Walker!

A well-deserved congratulations on a successful defense last week! The amazing work speaks for itself:
doi.org/10.1101/2025...
doi.org/10.1038/s415...
doi.org/10.1038/s415...
and more coming soon

Excited to follow her future success!

Huge congrats to Gabe Dolsten on a fantastic PhD defense last week!!! The 1st PhD from the lab! So proud of his many research achievements e.g.:
doi.org/10.1038/s415...
doi.org/10.1101/2025...
doi.org/10.1016/j.xg...

He's bound to do amazing things ahead!

Happy to present today at AAI Introduction to Computational Immunology Course today at UPenn

Temporal and context-dependent requirements for the transcription factor Foxp3 expression in regulatory T cells @natimmunol.nature.com @yuripritykin.bsky.social Rudensky @princetonupress.bsky.social @mskcancercenter.bsky.social www.nature.com/articles/s41...

Temporal and context-dependent requirements for the transcription factor Foxp3 expression in regulatory T cells - Nature Immunology Rudensky and colleagues demonstrate a context-dependent differential requirement for Foxp3 for Treg cell transcriptional and functional programs.

Our paper is out today at @natimmunol.nature.com! Very timely!
We performed extensive exploration of Foxp3 in Treg cells, using inducible protein degradation in vivo.
Wonderful collaboration led by Sasha Rudensky and Wei Hu, computation led by talented Gabe Dolsten.
Read it here: rdcu.be/eJ0hH

Extremely happy about the Nobel prize recognizing regulatory T cells! A fascinating concept with so many potential clinical applications.
Very lucky to have been working on the genomics of Treg cells in collaboration with the giant in the field, Sasha Rudensky @mskcc.bsky.social !

Excited to share our new study:
Single-cell multiomics reveals archetypal regulatory programs shared across CD4 and CD8 T cell subsets in viral infection
bioRxiv: doi.org/10.1101/2025...

🧵 Key findings below 👇

Metadomain and metaloop genome interactions in mammalian T cells https://www.biorxiv.org/content/10.1101/2025.09.19.677419v1

Single-cell multiomics reveals archetypal regulatory programs shared across CD4 and CD8 T cell subsets in viral infection T cells protect against pathogens and tumors and can differentiate into various functionally distinct subsets. While each subset exhibits a characteristic epigenomic and transcriptional profile, essen...

This work is a wonderful collaboration led by amazing Sarah Walker, with Joris van der Veeken and Sasha Rudensky.
More details in the preprint: doi.org/10.1101/2025...

Looking forward to any feedback! 🙌

In sum, we provide:
– A resource and framework for high-resolution T cell regulatory analysis.
– Archetypal regulatory decomposition of core T cell functions across lineages and infection contexts.
– Insights into shared regulatory logic of CD8 progenitors and CD4 Tfh cells.

A key challenge is to decompose regulatory programs driving overlapping core T cell functions e.g. self-renewal, expansion, cytotoxicity, cytokine production.
For this, we did archetypal analysis.
It revealed that CD8 progenitors combine CD8 exhaustion & CD4 Tfh archetypes.

Surprisingly, these progenitor CD8 T cells were transcriptionally & epigenomically most similar to CD4 Tfh (follicular helper) cells.
Despite distinct lineages, they shared activity of CXCR5, BCL6, TOX, TCF1, ID3 and PD-1.
This suggests converging cellular phenotypes.

Notably, fundamentally and translationally important Tcf1⁺ progenitor CD8 T cells formed a shared population across acute & chronic infection.
These results help reconcile recent studies of several related populations.

We profiled 31k+ T cells with scATAC+RNA-seq during acute & chronic viral infection and built a 285-sample ATAC-seq atlas.
This enabled robust identification of all major T cell states: naive, effector, memory, Treg, Tfh, exhausted & progenitor, shared across infection conditions.

Excited to share our new study:
Single-cell multiomics reveals archetypal regulatory programs shared across CD4 and CD8 T cell subsets in viral infection
bioRxiv: doi.org/10.1101/2025...

🧵 Key findings below 👇

ArchVelo: Archetypal Velocity Modeling for Single-cell Multi-omic Trajectories https://www.biorxiv.org/content/10.1101/2025.09.14.676182v1

Thanks Lee! In short, I think it's possible, and Drosophila is a good system for this, but the outcome depends on the loop. We described several classes, now working on a more detailed classification.
Some perturbations have already been reported, e.g. for tethering elements etc. but not at scale

Pritykin Lab Pritykin Lab at the Lewis-Sigler Institute for Integrative Genomics and the Department of Computer Science at Princeton University.

A wonderful collaboration with the Mike Levine &
Olga Troyanskaya labs!

More papers and preprints from the lab coming soon — stay tuned!

pritykinlab.github.io

We find 3D chromatin structures earlier than previously thought — before zygotic genome activation — and persisting through mitosis. Developmental elements linked to GAF/Zelda act as conserved bookmarks for gene regulation.

3D chromatin structures precede genome activation in Drosophila embryogenesis Dolsten et al. map the 3D chromatin architecture across early Drosophila development using high-resolution Micro-C, and, by integrative analysis with 149 public ChIP-seq datasets, identify four classe...

Happy to share our new paper!

We present high-resolution Micro-C maps across Drosophila embryogenesis, integrated with 149 ChIP-seq datasets. This systematic analysis enabled clustering of loops & boundaries into 4 distinct classes with distinct regulatory roles.

www.cell.com/cell-genomic...

Single-cell multiomics reveals archetypal regulatory programs shared across CD4 and CD8 T cell subsets in viral infection https://www.biorxiv.org/content/10.1101/2025.09.08.675014v1

Come talk to me at #ISMBECCB2025 this week if interested in this opportunity

Pritykin Lab Pritykin Lab at the Lewis-Sigler Institute for Integrative Genomics and the Department of Computer Science at Princeton University.

Comp bio postdoc positions available! Come work with us at Princeton University on computational method development and applications in regulatory genomics, genome editing, immunology and cancer, in mouse and human: pritykinlab.github.io#jobs
Please share among all those who may be interested!

After a long trip and a long sleep, i am ready to enjoy the rich scientific program at #ISMBECCB2025 in Liverpool. This is also the first year of our new COSI in Computational and System Immunology (CSI) happening on Tuesday. And of course looking forward RegSys, as usual with fantastic organizers

For CSI COSI, I am very thankful to my co-chair Jishnu Das and steering committee @yuripritykin.bsky.social, Hatice Ulku Osmanbeyoglu, Aly Azeem Khan. And everyone who submitted their for consideration for this session www.iscb.org/ismbeccb2025...