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...
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/...
ha, pool party! what a great name
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...
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.
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...
starting to suspect that we won't hear the outcome of the Research Ireland Investigators Stage 1 call by the end of January
Thanks to @researchireland.ie for funding, and to the DepMap teams @broadinstitute.org and @sangerinstitute.bsky.social for generating the data that our approach depends on 9/9
More broadly, we think this is a useful a foundation for cell line–specific prediction of synthetic lethality beyond paralog gene pairs. Paper's on @biorxivpreprint.bsky.social, predictions available on @figshare.com
figshare.com/articles/dat... 8/9
Using this approach, we generate a genome-scale map of predicted paralog pair dependencies across >1000 cell lines. This resource can be used to prioritise paralog pairs that will cause strong fitness defects in specific contexts (e.g. in HER2 amplified breast cancer models). 7/9
We identify multiple predictive features, including the expression and essentiality of the paralogs themselves and their interaction partners, allowing paralog buffering to be modeled in a cell line–specific network context. 6/9
However, this screening approach is not easily scalable. Instead, here we develop a machine-learning framework to predict pairwise paralog dependencies from existing single-gene CRISPR screening data — both which paralog pairs cause defects and in which specific cell lines. 5/9
One solution is to perform combinatorial CRISPR screens focused on paralogs, as has been done for subsets of paralog pairs in relatively small numbers of cell lines (<30). This has been very informative and has revealed context-specific paralog-pair dependencies. 4/9
A limitation of the DepMap is that it is currently based on single-gene perturbation screens. This is a problem for the ~70% of human genes with paralogs (duplicates). Because pairs of paralogs often share functions, many only cause a fitness defect when perturbed in combination. 3/9
The DepMap enables the discovery of genetic vulnerabilities associated with specific biomarkers and can inform drug development (e.g. identifying WRN as a vulnerability in microsatellite instability–high cells has led to multiple clinical trials of WRN inhibitors). 2/9
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
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.6...
all slightly different gene sets, but a lot of DDR factors
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...
thanks!
Great new work from @colmr.bsky.social predicts a cancer dependency map for paralogs: doi.org/10.64898/202....
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...
Photo containing the following text: "Their paper was published a year before Guyon defended her Ph.D. thesis, for which she had tested numerous algorithms for linear classification—but none of these was an optimal margin classifier, meaning the algorithms found some linear boundary, not necessarily the best one. Guyon could have used Krauth and Mézard's algorithm to implement an optimal margin classifier; she didn't. "One of the examiners of my Ph.D. asked me why I did not implement the algorithm of Mézard and Krauth and benchmark it against the other things I was trying. I said, 'Well, I didn't think it would make that much of a difference,'" Guyon told me. "But the reality is that I just wanted to graduate, and I didn't have time."
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)
yay! top of the to-read pile for January!
Merry Christmas, genetic interaction nerds:
www.biorxiv.org/content/10.6...
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...
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.
#Postdoc alert! We are looking for motivated individual with experience in computational systems biology to join our NetworkCommons initiative to benchmark and democratise network contextualisation methods across multiple applications. Deadline Dec 17th link here: tinyurl.com/yrrzxa94
Last chance to register. Hurry Up!
Anyone with a lower h-index than me is ineffectual, while anyone with a higher h-index is just better at playing the game and cutting corners. I'm sorry, that's just how numbers work!
