Maximilian Billmann

TF-MAPS: fast high-resolution functional and allosteric mapping of DNA-binding proteins Transcription factors (TFs) bind specific DNA sequences to control gene expression. Modulating TF activity is of considerable therapeutic interest but very few TFs have been successfully drugged. TF D...

TF-MAPS: fast high-resolution functional and allosteric mapping of DNA-binding proteins by @XianghuaLi2

Are Transcription Factors really 'undruggable'?

www.biorxiv.org/content/10.1...

Thank you @ioriolab.bsky.social for having me. It was great to talk science. @humantechnopole.bsky.social is truly a magnificent place to do research.

Systema: a framework for evaluating genetic perturbation response prediction beyond systematic variation - Nature Biotechnology An evaluation framework isolates perturbation-specific effects in perturbation datasets.

"...predicting responses to unseen perturbations is substantially harder than standard metrics suggest". I am not surprised. www.nature.com/articles/s41...

Genetic suppression features ABHD18 as a Barth syndrome therapeutic target - Nature The enzyme ABHD18 is shown to have a key role in cardiolipin metabolism in mitochondria, offering a potential route for a small-molecule treatment of the rare genetic disease Barth syndrome.

Can you find therapeutic targets for cardiomyopathies using simple, clean genetics in a human cell line? www.nature.com/articles/s41...

Combined MEK and PARP inhibition enhances radiation response in rectal cancer Xiao et al. use patient-derived rectal cancer organoids to identify that MEK inhibitors enhance radiation sensitivity by downregulating the DNA damage response protein RAD51. They find synergy with combined PARP inhibition in different preclinical models, thereby offering a promising regimen and potential future alternative to conventional chemoradiation in locally advanced rectal cancer.

Online now: Combined MEK and PARP inhibition enhances radiation response in rectal cancer

Thank you @colmr.bsky.social for the shoutout! It was quite a journey. If it is only nearly as useful as the @depmap.org we are happy. In any case, it complements this data ...as expected!?

Large-scale CRISPR screening in primary human 3D gastric organoids enables comprehensive dissection of gene-drug interactions Nature Communications - CRISPR-Cas9-based screens have allowed the study of gene-drug interactions. Here, the authors develop CRISPR-Cas9 knock-out, activation and repression screens in human...

rdcu.be/eBl5k

RNA Pol II inhibition activates cell death independently from the loss of transcription When RNA polymerase II (RNA Pol II) is inhibited, the inhibition is sensed and signaled to mitochondria, leading to programmed cell death independently of the loss of RNA Pol II transcription activity...

I’m excited to highlight our latest paper, just published in Cell 🎉

We report the existence of a previously uncharacterized signaling pathway that is responsible for activating cell death upon loss of gene expression.

1/n 🧪

www.cell.com/cell/fulltex...

Variant characterization in the intrinsically disordered human proteome Variant effect prediction remains a key challenge to resolve in precision medicine. Sophisticated computational models that exploit sequence conservation and structure are increasingly successful in t...

Variant characterization in the intrinsically disordered human proteome - here is how we did it using short linear motif prediction, AlphaFold, and experimentation. Check out our preprint: www.biorxiv.org/cgi/content/...

One thing that really bothers me with the new "virtual cell" terminology is that it is currently largely focused on a very narrow definition of models that can predict effects of trans perturbations (gene dosage, drugs etc) on gene expression. 1/

Mapping MAVE data for use in human genomics applications - Genome Biology Background Experimental data from functional assays have a critical role in interpreting the impact of genetic variants. Assay data must be unambiguously mapped to a reference genome to make it access...

We are pleased to announce the publication of our manuscript "Mapping MAVE data for use in human genomics applications" in Genome Biology! 🧵 1/3 genomebiology.biomedcentral.com/articles/10....

agree.

Our "Atlas of Variant Effects 2030 Roadmap" is live: zenodo.org/records/1542...

1/n

Jason Moffat at #VariantEffect25

Have you discovered the Night Science Podcast yet?
@nightsciencepod.bsky.social

Kind words from one of the up-and-coming leaders of the field ;)

Thanks @colmr.bsky.social ! I felt this was a suitable place to recognize the substantial efforts that go into perturbation experiments.

I appreciate the recognition! I guess pertomics mostly describes a reverse genetics view and "buffomics" would place the phenotype in the center ;)