Colm Ryan
@colmr.bsky.social
Systems biology | Bioinformatics | Cancer | Genetic interactions https://cancerdata.ucd.ie/ (he / him)
more complexity in translating synthetic lethal interactions. "interactions observed in vector-based models are often a consequence of IDHmut protein overexpression..." www.sciencedirect.com/science/arti...
Targeting vulnerabilities in IDH mutant tumours: The model matters
Synthetic lethal interactions with IDH1 and IDH2 (IDH) mutations were identified in non-endogenous IDH mutant (IDHMUT) AML and glioma models, but are …
sciencedirect.com
🧬NEW PAPER🧬 To what extent is cancer development deterministic? Does the germline genome affect that predictability? Find out in our #StrainDifferences paper @nature.com "Genetic background sets the trajectory of experimental cancer evolution" www.nature.com/articles/s41... 🧵[1/14]
Genetic background sets the trajectory of experimental cancer evolution - Nature
Experimentally replaying tumour evolution in divergent mouse strains reveals the importance of interactions between genetic ancestry and acquired cancer-driving mutations in shaping the earliest stage...
nature.com
Preprint alert! 🚨 We are very excited to share our new manuscript on Bohring-Opitz syndrome, a devastating rare monogenic disorder driven by truncating variants in ASXL1. This project was led by PhD student Emma Doyle, one of the OG Conway lab members 💪. 1/6 www.biorxiv.org/content/10.6...
Divergent Pathogenic PR-DUB Complex Variants Converge Functionally Via PRC2 Displacement From Chromatin
The PR-DUB complex is responsible for erasing the repressive histone modification, H2AK119ub1. ASXL1-3 proteins are mutually exclusive catalytic partners of BAP1 in the PR-DUB complex. Somatic heteroz...
biorxiv.org
Benchmarks of AI agentic systems remind me of bioinformatics 20 years. And not in a good way! Is anyone else getting tired of everyone reporting that they are better than everyone else according to their own new benchmark? 🤬
New preprint from the group, comparing CRISPRko and CRISPRi via a Perturb-seq readout: www.biorxiv.org/content/10.6...
Direct comparison of CRISPR knockout and interference with Perturb-seq
CRISPR knockout (CRISPRko) and CRISPR interference (CRISPRi) are two workhorse technologies for loss-of-function studies, yet direct comparisons between the two are scant relative to their widespread ...
biorxiv.org
💙💛 Our warmest congratulations to UCD Professor Cormac Taylor, who has been named the recipient of The Physiological Society’s 2027 Widening Participation in Physiology Prize Lecture.
With lab members from both France and Spain, I have to hope for an unprecedented draw in this evening’s semifinal. Perhaps both teams will shake hands, acknowledge how good they both are, and then go for a celebratory smoothie.
Nicely caveated science reporting from the Guardian – 'Thirty is pretty arbitrary', 'scientists still don’t know exactly what a “healthy” microbiome looks like' www.theguardian.com/lifeandstyle...
Is it true that … we should eat 30 plants a week?
A growing supplements market may be trying to capitalise on this claim, but the truth is we still don’t know what a truly healthy gut microbiome really looks like
theguardian.com
Very saddened to learn that @wellcometrust.bsky.social has decided to no longer fund Irish researchers through their discovery grants. This is a major blow for those who do truly blue skies research in Ireland as the ecosystem (i.e. @researchireland.ie) only funds research with perceived "impact"!
Another genetic interaction map of the DNA Damage Response. That makes six maps now! www.biorxiv.org/content/10.6...
Mapping the genetic landscape of the DNA damage response with Cas12a-based combinatorial knockout screens
The DNA damage response (DDR) is a complex network of cellular pathways that ensures the faithful maintenance of our genomes upon a wide array of genomic insults. To elucidate the functional architect...
biorxiv.org
Colm Ryan@colmr.bsky.social · 6mo agoAnother genetic interaction map of DNA repair factors! I think that makes 5 GI maps (including preprints) of DNA Damage / Repair related factors? Potentially enough to do some systematic comparisons. www.sciencedirect.com/science/arti...
My letter to Minister Lawless about Research Ireland's decision to devolve the awarding of doctoral scholarships & postdoctoral fellowships to universities. A disastrous move. Please consider raising this issue in your own institutions and with elected representatives and the media.
Now out in Genome Medicine link.springer.com/article/10.1... Work led by the brilliant Elle Loughran (not on bsky) on the evolution of hypodiploid tumours, who is heading to Montpellier this week to start a postdoc with @aline-muyle.bsky.social!
bioRxiv Cancer Bio@biorxiv-cancer.bsky.social · 12mo agoPervasive Chromosomal Instability Drives the Karyotypic Evolution of Hypodiploid Tumours https://www.biorxiv.org/content/10.1101/2025.08.08.668983v1
Some thoughts on where AI in genomics stands right now, building on a symposium we recently hosted at UChicago. Seven points, ranging from why scaling DNA models hasn't delivered, to why metadata is the real bottleneck, to the weird backlash against AI in academia open.substack.com/pub/blekhman...
Seven points on the current state of AI in genomics
A grounded take from the messy middle of an AI revolution
open.substack.com
Thinking about applying for an MSCA postdoctoral fellowship? The UCD School of Medicine has a list of academics keen to support applicants. I'm one – looking for people interested in synthetic lethality, paralogs in disease, or LLMs for genotype-phenotype analysis. www.ucd.ie/medicine/res...
EoI for MSCA Postdoctoral Fellowships - UCD School of Medicine
ucd.ie
If you are interested in PARP inhibitors and history, this might be of interest to you. www.nature.com/articles/s41.... An attempt to cover the work of thousands and their immense contributions to the development of a targeted approach to treating cancers.
Two decades of PARP inhibitor synthetic lethality in cancer - Nature
The past two decades of PARP inhibitor synthetic lethality in cancer is explored.
nature.com
We have started a project trying to predic the interactions/structures of all yeast protein pairs using an AlphaFold pooling approach. We are making the current dataset open and we welcome collaborations. www.evocellnet.com/2026/03/mapp...
Mapping the yeast atructural interactome with AlphaFold3: an open call for collaboration
We are excited to announce the early-stage release of our S. cerevisiae structural interactome mapping project. Using AlphaFold3 (AF3), w...
evocellnet.com
Our thoughts, impressions, and presentations of the "2nd EuroDepMap symposium" in Milan (Nov 2025) are online at @febsletters.bsky.social. febs.onlinelibrary.wiley.com/doi/10.1002/...
FEBS Press
Held on 20 November 2025 at Human Technopole in Milan, the 2nd European Cancer Dependency Map Symposium convened experimental and computational scientists to discuss how cancer dependency mapping in ...
febs.onlinelibrary.wiley.com
We are very happy to see our study finally appear online @nature.com! This has been work of nearly 10 years in collaboration with the National Institute of Genome Medicine 🇲🇽, the National Cancer Institute 🇲🇽, the @sangerinstitute.bsky.social and others ⬇️ www.nature.com/articles/s41...
Ancestry and somatic profile indicate acral melanoma origin and prognosis - Nature
Analysis of the somatic and transcriptomic profile of 123 acral melanoma samples from Mexican patients helps understand tumour origins and prognosis, and highlights the importance of including samples...
nature.com
Our preprint is now published in MSB. link.springer.com/article/10.1... We decompose multi-omics into distinct phenotypic axes (drug response vs ARID1A-driven cell state), improving interpretation and revealing how baseline cell state rewires signaling and shapes MAPK inhibitor resistance.
Integrative multi-omics defines melanoma drug response networks and ARID1A-dependent resistance mechanisms - Molecular Systems Biology
Resistance to BRAF/MAPK inhibitors is a significant challenge in melanoma treatment, driven by adaptive and acquired mechanisms allowing tumor cells to evade therapy. We explored early signaling respo...
link.springer.com
Evangelia Petsalaki@epetsalaki.bsky.social · 2y agoNew preprint from our group @ebi.embl.org and the Vidal-Puig group! We combined pseudotemporal ordering of cross sectional MASLD patient data with network analysis to describe the disease progression and identify a signature of 24 plasma biomarkers for patient staging www.biorxiv.org/content/10.1...
And more isogenic CRISPR screens coming out of Toronto @sickkidsto.bsky.social, this time by Mike Tyers and team - congrats! www.biorxiv.org/content/10.6...
biorxiv.org
starting to suspect that we won't hear the outcome of the Research Ireland Investigators Stage 1 call by the end of January
New paper from Narod Kebabci – “A predicted cancer dependency map for paralog pairs” www.biorxiv.org/content/10.6... Background: The Cancer Dependency Map from @depmap.org is a fantastic resource that characterises genetic dependencies at genome-wide scale across ~1,000 cancer cell lines. 1/9
A predicted cancer dependency map for paralog pairs
Background Genome-wide CRISPR screening has enabled the development of dependency maps in hundreds of cancer cell lines, facilitating the identification of genetic vulnerabilities associated with specific biomarkers. Paralogs, despite being common drug targets, are often missed in these screens as their individual disruption rarely causes a significant fitness defect. Combinatorial screens have revealed that paralog pairs are often synthetic lethal but that these effects are highly context specific. To develop paralogs as therapeutic targets we must identify which paralog pairs are synthetic lethal in which cancer contexts. Results We develop a machine learning classifier to predict cell-line specific synthetic lethality between paralog pairs. We demonstrate the utility of features derived from the cell-line specific expression and essentiality of the pair and their protein-protein interaction partners for this purpose. We evaluate our predictions across multiple scenarios: predicting for the same pairs in unseen cell lines, for new gene pairs in seen cell lines, and for entirely uncharacterized pairs in unseen cell lines. We show that we can make predictions across all scenarios. We validate our predictions using independent combinatorial CRISPR screens and show that the agreement between our predictions and published experiments approaches the agreement across experiments. Conclusions Our classifier predicts cell-line-specific synthetic lethality between paralog pairs and provides insights into the underlying features driving these interactions. We make our predictions for 1,005 cell lines available as a resource to facilitate the discovery of context-specific paralog synthetic lethalities and to guide the design of more targeted combinatorial screens. ### Competing Interest Statement The authors have declared no competing interest. Research Ireland, 20/FFP-P/8641, 18/CRT/6214
biorxiv.org
Another genetic interaction map of DNA repair factors! I think that makes 5 GI maps (including preprints) of DNA Damage / Repair related factors? Potentially enough to do some systematic comparisons. www.sciencedirect.com/science/arti...
Uncovering genetic interactions in the DNA repair network in response to endogenous damage and ionizing radiation
Genomic integrity relies on a complex network of DNA damage response (DDR) pathways that repair endogenous and exogenous lesions, yet how individual f…
sciencedirect.com
Great new work from @colmr.bsky.social predicts a cancer dependency map for paralogs: doi.org/10.64898/202....
doi.org
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.
very sad news. Peer Bork was one of the leaders of our field, a wonderful scientist, and he's much too young to be gone. www.embl.org/news/embl-an...
In remembrance of Peer Bork | EMBL
EMBL and its community are deeply saddened by the death of Peer Bork, the organisation’s Interim Director General.
embl.org
Enjoying 'Why Machines Learn' by Anil Ananthaswamy, including this anecdote highlighting that there's always more that *could* be in a PhD but that you have to draw a line somewhere. Guyon here is Isabelle Guyon, who was later key to the development of SVMs (especially the kernel trick)
Merry Christmas, genetic interaction nerds: www.biorxiv.org/content/10.6...
Functional modules predict cancer-relevant genetic interactions in mammalian cells
Genetic interactions can reveal gene function and identify cancer-relevant synthetic lethals, but systematic mapping in human cells is constrained by inefficient reagents, vast combinatorial search sp...
biorxiv.org
Great to see this out, collaboration with the Bond lab @sysbioire.bsky.social to understand consequences of EZH2 mutation in T-acute lymphoblastic leukaemia (T-ALL). Congrats to @lefeivret.bsky.social @cosmintudose.bsky.social and other authors not on bluesky! ashpublications.org/bloodadvance...
Reduced PRC2 function causes asparaginase resistance in T-ALL by decreasing WNT pathway activity
Key Points. Reduced PRC2 function in T-ALL is associated with asparaginase resistance that is linked to reduced WNT/STOP pathway activity.Asparaginase resi
ashpublications.org
Replacing my still functioning 2017 Mac because it's no longer compatible with our two factor authentication software (preventing me logging on to any work related system). This really doesn't seem optimal.
