Deirdre O'Sullivan

Tri-Institutional Computational Biology and Medicine PhD candidate | @thenormanlab @ MSKCC | Functional Genomics Tech Dev

[Karthik Guruvayurappan @somet3000]

Super excited to share what we have been working on at the intersection of human genetics and Perturb-seq!

Check out Tom's tweetorial below for more details!

[Thomas Norman @thenormanlab]

1/ Most genes and variants matter somewhere but look silent in any one cell model. Can we build conditions that reveal phenotypes? With @kanishkadey, we engineer cell states to expose hidden disease biology and trace how genetic risk reaches disease genes. https://t.co/pUHPPjxTkX

[Thomas Norman @thenormanlab]

My lab at MSKCC in New York is hiring for two positions. Join us at the frontier of functional genomics, studying fibroblast state transitions, combinatorial genetics, and ECM in disease. Please share with anyone who might be a good fit! (Mustache not required.)

[Thomas Norman @thenormanlab]

In my excitement I forgot to actually link the preprint!

https://t.co/BCSkTy9242

[Thomas Norman @thenormanlab]

CAP cloning instead assembles and amplifies linear DNA in vitro, then uses TelN protelomerase to generate exonuclease-resistant, covalently closed molecules that package directly into lentivirus.

(Shoutout to Touchlight who pioneered this chemistry.)

[Thomas Norman @thenormanlab]

New preprint on technologies to scale up CRISPR screens.

We use them to map 665,856 pairwise genetic perturbations and outline a path to comprehensive interaction mapping in human cells.

We also introduce an approach for cloning lentiviral libraries with billions of elements.

[bioRxiv SysBio @biorxiv_sysbio]

Scaling perturbations: beyond genome-scale CRISPR screens https://t.co/uMbQTXqjuM #biorxiv_sysbio

[Divya Koyyalagunta @divyakoyy]

✨Our paper on inferring patterns of metastatic spread is out in @naturemethods!

Super grateful to mentors @quaidmorris and @KarunaMDPhD, and the Tri-I CBM PhD program @cbm_student!

[Thomas Norman @thenormanlab]

Our paper is now out in final form at Nature Genetics! For those who missed the preprint, we used large-scale Perturb-seq targeting transcription factors to push primary fibroblasts into diverse transcriptional states, including those observed in cell atlas studies.

[Thomas Norman @thenormanlab]

There’s more to come in this space, but I am thrilled to see this work finally published. Huge thanks to first authors @ricocardy and @kmsouthard, and co-authors @tang_anran, @deirdreosull, @elimetzner, and @somet3000.

[Thomas Norman @thenormanlab]

Our Multiome Perturb-seq paper is now out in @CellSystemsCP! As discussed in my thread on the preprint, this is an approach for linking CRISPR-mediated genetic perturbations to their effects on cellular chromatin state and gene expression. https://t.co/SeqTCGM6vH

[Tri-I CBM @cbm_student]

Tri-i CBM held our annual retreat 10/27-28. We welcomed the new first years, had wonderful talks and discussions, and enjoyed rejuvenating group bonding time⭐️!

Application portals are now open for perspective applicants, and we invite you to join our CBM family!

[Deirdre O'Sullivan @deirdreosull]

Comprehensive transcription factor perturbations recapitulate fibroblast transcriptional states https://t.co/CLlkVpmANz

[Thomas Norman @thenormanlab]

Can we recreate the transcriptional states seen in single-cell atlas projects? In our new preprint we try to do this using large-scale Perturb-seq experiments. Along the way we discuss off-target effects of CRISPR epigenetic editors and identify drivers of key fibroblast states.

[Thomas Norman @thenormanlab]

https://t.co/hld6hmGfyG

[Thomas Norman @thenormanlab]

Excited to share our preprint "Multiome Perturb-seq unlocks scalable discovery of integrated perturbation effects on the transcriptome & epigenome". This work extends single-cell CRISPR screens to simultaneously profile gene expression & chromatin accessibility.

[Thomas Norman @thenormanlab]

https://t.co/rtwDRGoIWU

[Deirdre O'Sullivan @deirdreosull]

@mmdarmofal 🎉🎉🎉

[Deirdre O'Sullivan @deirdreosull]

@ATGmsalickTAG !!!!

[Ivy Zhang @ivyzhang__]

Interested in predicting mutational impact on protein:protein binding?

Our new preprint provides a workflow (using open-source software, Perses) for running free energy calculations on protein:protein complexes, focusing on diagnosis of sampling issues: https://t.co/Ww7W7cJY5l