Check out our new article if you are interested in disorder-mediated protein interactions, AlphaFold-based structural modeling and variant characterization: Https://rdcu.be/fw2oz Dx.doi.org/10.1038/s41594-026-01846-z

Variant characterization in the intrinsically disordered human proteome - Nature Structural & Molecular Biology

Proteome-wide prediction and structural modeling of disordered protein interaction interfaces advance characterization of disease-associated variants in disordered protein regions.

dx.doi.org

Excited that the final version of our experimental assessment of AI protein interaction predictions is out: www.nature.com/articles/s41... Brief summary below:

Experimental assessment of AI-based interactome mapping - Nature Communications

AlphaFold’s success in protein structure predictions has led to similar attempts to predict interactomes. Here, the authors demonstrate that AI-based screens are very limited in discovering truly nove...

nature.com

Yours truly is a proper scientist now! TL;DR: we used AI to redesign parts of essential cell machinery with only 19 canonical amino acids instead of 20. Why? Great thread by @harriswang.bsky.social provides more context and details. Let me talk a bit about the AI design part of this. 1/

Harris Wang@harriswang.bsky.social · 3mo ago

1/ Excited to share our new paper in Science @science.org: “Toward life with a 19-amino acid alphabet through generative artificial intelligence design.” A great collab w/ Sergey's group @sokrypton.org at MIT @columbiasysbio.bsky.social science.org/doi/10.1126/... 🦠🧬🛠️🖥️💥

New work led by Hasan Cubuk: moving from interpreting variants individually to combining both alleles in recessive disease. DMS of >8000 ADSL variants → inferred enzyme activity → additive biallelic scores that track patient phenotypes. Great collab with the Kudla lab! www.cell.com/cell-systems...

Mechanistic modeling of recessive disease through allelic integration of variant effects

Recessive diseases arise from the combined effects of two alleles, yet most variant interpretation methods consider variants individually. Çubuk et al. map more than 8,000 variants in the recessive en...

cell.com

Out Now! Effector–host interactome map links type III secretion systems in healthy gut microbiomes to immune modulation #MicroSky

Effector–host interactome map links type III secretion systems in healthy gut microbiomes to immune modulation

Nature Microbiology, Published online: 26 January 2026; doi:10.1038/s41564-025-02241-yLarge-scale computational and in vitro analyses identify commensal type III secretion systems and substrates in the human gut microbiome that can interact with human proteins to modulate immune pathways.

go.nature.com

Very happy and proud that our paper “Effector–host interactome map links type III secretion systems in healthy gut microbiomes to immune modulation” is out today in #NatureMicrobiology @natmicrobiol.nature.com Paper 👉 t1p.de/v42xb #microbiome #commensal #pathomechanism #T3SS #immune #health #IBD

Effector–host interactome map links type III secretion systems in healthy gut microbiomes to immune modulation - Nature Microbiology

Large-scale computational and in vitro analyses identify commensal type III secretion systems and substrates in the human gut microbiome that can interact with human proteins to modulate immune pathwa...

t1p.de

delighted to share our review, out today in @cp-trendsgenetics.bsky.social! check it out if you're curious about how recent advances in technology & biology have contributed to our understanding of how alternative isoforms diversify the proteome.

Trends in Genetics@cp-trendsgenetics.bsky.social · 8mo ago

"Beyond the Gene: Decoding Alternative Isoforms" by Kaia Mattioli (@kaiamattioli.bsky.social) & Martha Bulyk "The degree to which alternative isoforms actually contribute to the complexity of the human proteome in their endogenous contexts has been the subject of much debate..." shorturl.at/YbNoB

I am happy to finally share this preprint of my PhD project in @guillaumediss.bsky.social lab at the FMI in Basel. We used ddPCA to map the genetic architecture of the entire human bZIP interaction network. www.biorxiv.org/content/10.1... Thanks to all our co-authors for the great collaboration!

The genetic architecture of the human bZIP family

Generative biology holds the promise to transform our ability to design and understand living systems by creating novel proteins, pathways, and organisms with tailored functions that address challenge...

biorxiv.org

Excited to share this collaborative review with @dsegre.bsky.social and @devmoy.bsky.social. We discuss common issues with context-specific genome-scale metabolic network models and provide recommendation for future model development.

Daniel Segrè@dsegre.bsky.social · 12mo ago

Just published @cp-trendsbiotech: Flux sampling and context-specific genome-scale metabolic models for biotechnological applications: www.cell.com/trends/biote... by @devmoy, with @fuxmanlab

Exited to share our recent work on viral cis-regulatory elements in collaboration with @tewhey.bsky.social! We identified >2000 CREs across the genomes of 27 human-infecting dsDNA viruses from the Herpesvirus, Adenovirus, Papillomavirus, and Polyomavirus families. www.biorxiv.org/content/10.1... 1/8

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/...

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...

biorxiv.org

Congrats to Renata Goncalves who led a study in Gokhan Hotamisligil's lab that has just come out in Nature - ably assisted by Jillian Riveros! www.nature.com/articles/s41...

CoQ imbalance drives reverse electron transport to disrupt liver metabolism - Nature

Reverse electron transport is the mechanism behind excess mitochondrial reactive oxygen species in the livers of obese mice, which has implications for developing therapeutics for fatty liver dis...

nature.com

Widespread variation in molecular interactions and regulatory properties among transcription factor isoforms

Widespread variation in molecular interactions and regulatory properties among transcription factor isoforms

Lambourne, Mattioli, Santoso, et al. compare protein isoforms of the same transcription factor genes through high-throughput profiling of DNA-binding, protein-binding, activation, localization, and condensate formation. Differences between isoforms are widespread, often unpredictable from sequence differences, and inform a disease-associated categorization of alternative isoforms into rewirers or negative regulators.

dlvr.it

Online Now: Widespread variation in molecular interactions and regulatory properties among transcription factor isoforms Online now:

Widespread variation in molecular interactions and regulatory properties among transcription factor isoforms

Lambourne, Mattioli, Santoso, et al. compare protein isoforms of the same transcription factor genes through high-throughput profiling of DNA-binding, protein-binding, activation, localization, and condensate formation. Differences between isoforms are widespread, often unpredictable from sequence differences, and inform a disease-associated categorization of alternative isoforms into rewirers or negative regulators.

dlvr.it

reposting the 🧵 from the other site that I wrote when the preprint came out: TFs, like most genes, are frequently expressed as a series of multiple distinct isoforms. these isoforms (by definition) differ in sequence -- often in annotated protein domain regions (e.g. DNA-binding & effector domains)

The published version of our transcription factor isoforms survey is online www.sciencedirect.com/science/arti... we cloned 100's of isoforms (that arise through alternative splicing etc.) testing them in high-throughput assays for DNA-binding, protein-binding, activation, and more.

our work on the molecular differences between transcription factor isoforms is out now in Molecular Cell! key point: 2/3rds of TF isos differ in properties like DNA binding & transcriptional activity many are "negative regulators" & misexpressed in cancer www.sciencedirect.com/science/arti...

As the first measles death in the US since 2015--an unvaccinated child--is reported, let us read the thoughts of our new Secretary of Health and Human Services on this disease. www.reuters.com/world/us/fir... (Foreword to "The Measles Book", 2021)

On Wednesday 2/26, I’ll be in Boston to give a Harvard Science Book Talk. I’ll have a marvelous relic of aerobiological history to unveil. Details here: www.harvard.com/event/carl-z... 3/5

The STARLING has landed - excited to share new work from @bornanovak.bsky.social and @jefflotthammer.bsky.social in what is also Borna's first Bluesky post! If you're at BPS, I'll be speaking about this this afternoon in IDP SG, and Borna and Jeff both have posters (Sunday B112 and Wed B152).

Borna Novak@bornanovak.bsky.social · last yr.

Excited to announce the newest member of the flock - STARLING (conSTruction of intrinsicAlly disoRdered proteins ensembles efficientLy vIa multi-dimeNsional Generative models). www.biorxiv.org/content/10.1...

Interested in learning about biases in protein-protein interface predictions with AlphaFold2? Check out our new review on this topic: authors.elsevier.com/a/1kbSa_,2Bd...

Btw, the abstract deadline has been extended to Jan 27!

Pascal Falter-Braun@interactome.bsky.social · 2y ago

Hey #networkbiology bubble and affinionados. Don't miss the CSHL Meeting: Network Biology in spring 2025. Great panel of speakers lined up by the organizers @fritzroth.bsky.social @pedrobeltrao.bsky.social, Roded Sharan, and @jsvanleeuwen.bsky.social. meetings.cshl.edu/meetings.asp...

🧪 If you are a network (or network-curious!) biologist, please consider attending the upcoming CSHL Network Biology Meeting. Details + abstract deadline below!

CSHL Meetings@cshlmeetings.bsky.social · 2y ago

FYI 🔔The abstract deadline for #cshlnetworks is coming up - Jan. 27th! Register to submit your abstract here: bit.ly/40cIfSl @fritzroth.bsky.social @jsvanleeuwen.bsky.social @pedrobeltrao.bsky.social

Can a single small molecule rescue the stability of nearly all mutations in a protein? Our new preprint by Taylor Mighell www.biorxiv.org/content/10.1... thread on the other place: x.com/taylor_mighe...

A pharmacological chaperone stabilizer rescues the expression of the vast majority of pathogenic variants in a G protein-coupled receptor

Reduced protein stability is the most frequent mechanism by which rare missense variants cause disease. A promising therapeutic avenue for treating destabilizing variants is pharmacological chaperones...

biorxiv.org