Colm Ryan

We still can’t predict much of anything in biology Biology is hard. Yes, even for AI.

Biology is much more complicated than most non-biologists can imagine. And AI is not going to change this anytime soon.
blog.genesmindsmachines.com/p/we-still-c...

We think this work will be useful for 1) those choosing an existing method to score a genetic interaction screen and 2) those developing new genetic interaction scoring systems as it provides a framework for benchmarking. Thanks to @researchireland.ie for funding!

We find that no single method performs best across all screens, but one (Gemini) performs well across most and has an available R package (Gemini).

1) we develop a benchmark that allow us to compare the performance of different scoring methods when applied to a single screen and 2) we systematically apply this benchmark to 5 scoring methods applied across 5 published screens.

Multiple methods for scoring genetic interactions from combinatorial screens have been published, but comparison across methods has been limited. Most published screens use distinct scoring methods, making comparison across published work difficult. Here we make two contributions....

Benchmarking genetic interaction scoring methods for identifying synthetic lethality from combinatorial CRISPR screens Abstract. Synthetic lethality (SL) is an extreme form of negative genetic interaction, where simultaneous disruption of two non-essential genes causes cell

Hamda's paper is out: benchmarking different genetic interaction scoring methods for identifying synthetic lethal interactions from combinatorial CRISPR screens.

academic.oup.com/nargab/artic...

Synthetic lethality in cancer drug discovery: challenges and opportunities Nature Reviews Drug Discovery - This Review outlines recent advances in synthetic lethality, from CRISPR-based discovery and machine learning-guided prioritization of gene pairs to new phenotypic...

Enjoyed writing this review of synthetic lethality in drug discovery with @emanuelvgo.bsky.social and @davidjadams.bsky.social rdcu.be/eFBmw

PDTF - Homologous Recombination Defective Cancers ( Profs Chris Lord and Andrew Tutt) in Chelsea | The Institute of Cancer Research View details and apply for this PDTF - Homologous Recombination Defective Cancers ( Profs Chris Lord and Andrew Tutt) vacancy in Chelsea . Salary: Dependent on relevant Postdoctoral exp...

We're hiring ! Specifically....we are seeking to appoint a creative and motivated Postdoctoral Training Fellow to study how drug resistance emerges in homologous recombination defective (HRD) breast cancers and how this could be targeted. jobs.icr.ac.uk/vacancies/13...

2nd European Cancer Dependency Map Symposium - Human Technopole The 2nd European Cancer Dependency Map Symposium is a scientific event open to the national and international scientific community working in computational genomics, pharmacogenomics, and therapeutic ...

📢 The 2nd European Cancer Dependency Map Symposium is coming!
🗓️ 20 Nov 2025
📍 Human Technopole, Milan
Join us for a one-day dive into:
🔹 Cancer genomics
🔹 CRISPR screening
🔹 AI-driven target discovery
With the patronage of AIRC
🔗 humantechnopole.it/en/trainings...

Join Us! @ioriolab.bsky.social

Diverse epigenomic mechanisms underpin transcriptional dysregulation in Polycomb-altered acute myeloid leukemia Background Polycomb Repressive Complex 2 (PRC2) modulates chromatin accessibility and architecture to direct tissue-specific gene expression. PRC2 function is frequently altered in cancer by loss-of-f...

Pleased that the 2nd part of my PhD is now available as a preprint! Here, we investigated the epigenomic and transcriptomic changes occurring upon PRC2 depletion in AML cells. biorxiv.org/content/10.1.... A thread🧵1/17

Balancing off-target and on-target considerations for optimized Cas9 CRISPR knockout library design The continued development of high-dimensional CRISPR screen readouts, such as single-cell RNA sequencing and high-content imaging, necessitates compact libraries to enable functional interrogation at ...

Doomscrolling pause to chat CRISPR libraries! Preprint describes our new, data-driven approach to combine on-target and off-target predictions much more intelligently for *selecting* guides, which we use to develop our newest Cas9 knockout library, Jacquere. Thread: www.biorxiv.org/content/10.1...

just a month to go until the International Conference on Systems Biology #ICSB2025 kicks off in Dublin, still time to submit a poster abstract!

Diverse epigenomic mechanisms underpin transcriptional dysregulation in Polycomb-altered acute myeloid leukemia Background Polycomb Repressive Complex 2 (PRC2) modulates chromatin accessibility and architecture to direct tissue-specific gene expression. PRC2 function is frequently altered in cancer by loss-of-f...

new from @cosmintudose.bsky.social What happens when tumor suppresor EZH2 is mutated in acute myeloid leukaemia? How does it change transcription, chromatin accessibility & drug response? The Bond lab created CRISPR mutants to find out & Cosmin put it all together www.biorxiv.org/content/10.1...

montage of figures from the article and headshots of the authors

Article by Pádraig Cunningham and Barry Smyth in Communications of the ‪@acm.org‬ analyses the differences in quality and practices of new Open Access and traditional Computer Science journals. bit.ly/41KKQ7s

UCD co-lead breakthrough discovering genetic mechanism driving Weaver syndrome

Delighted that our work on EZH2 dominant negativity in Weaver syndrome is now out in Genes & Development!

This exciting work on chromatinopathies 🧬 was in collab with @adrianbracken.bsky.social and spearheaded by Orla Deevy.

@ucddublin.bsky.social @ucd-sbbs.bsky.social

www.ucd.ie/newsandopini...

Final year PhD students, I know you’re desperately trying to finish experiments/revisions/submissions/write a thesis & just survive - but please spare a few minutes to apply to your dream postdoc labs.

It easily takes A YEAR from first contact, even if everything goes to plan on both sides.

looks like a super resource, congrats on getting it out! I think having a large number of GIs measured in a single genetic background will be a really useful complement to DepMap. we're only starting to dig into the data now, will let you know how we get on!

A global genetic interaction map of a human cell reveals conserved principles of genetic networks We generated a genome-scale, genetic interaction network from the analysis of more than 4 million double mutants in the haploid human cell line, HAP1. The network maps ∼90,000 genetic interactions, in...

Monumental effort from @maxbillmann.bsky.social and colleagues, quantifying genetic interactions among 4 million human gene pairs. Lots of features associated with genetic interaction & GI degree conserved from yeast. www.biorxiv.org/content/10.1...

I too am 'programming' with Claude! it's fun isn't it?

Autocrine interferon poisoning mediates ADAR1-dependent synthetic lethality in BRCA1/2-mutant cancers Nature Communications - The RNA editing enzyme ADAR1 blocks interferon responses triggered by cytosolic RNA sensors, and has been proposed as a potential target in immuno-oncology. Here, the...

With super Roman Chabanon and Sophie Postal Vinay, we show that inhibition of RNA editor ADAR1 causes a new form of BRCA synthetic lethality>autocrine inferferon poisoning. Relevant for ADAR1 drug discovery. Could provide a mechanistically different approach than PARPi. rdcu.be/eyo6t

This is one of those awesome "I always wanted to do that experiment" papers. And a great 🧵.

congrats Tríona!

when an Irish funding agency launches a new grant call in July with a deadline in August it's hard to feel that researcher well-being is one of their priorities...

I'm not the person to ask!

The final day of #ICSB2025 on Thurs, Oct 9, will finish with 3 more outstanding breakout sessions.
✨Clinical Decision Support Tools
✨Evolution & Development
✨AI/ML Approaches in Systems Biology

For more info: bit.ly/4mPNfGQ
@ucddublin.bsky.social @ucd-chas.bsky.social @precisiononcire.bsky.social

I'm in School of Medicine, you would need to approach a relevant School/Department in one of the Irish universities

Research Ireland's remit is broad, so I can't see why not. You would need to find a host institute www.ucd.ie/music/

Unexpectedly, @jurgjn.bsky.social found that running Alphafold3 predictions for protein interactions can yield ipTM scores that are more predictive of true interactions when run in pools of proteins instead of pairwise predictions. Presumably, this reflects some sort of "competition effect".

School of Medicine @ucddublin.bsky.social are interested in expressions of interest. Note that the deadline is relatively tight – 28th August