Stefan Holderbach
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sholderbach.bsky.social
Stefan Holderbach
@sholderbach.bsky.social
Playing with programming languages, proteins, and photography. Nerding out about Nushell and niche applications of synthetic biology.
Reposted by Stefan Holderbach
September 16, 2025 at 2:40 PM
Reposted by Stefan Holderbach
Rust 1.90.0 is out! blog.rust-lang.org/2025/09/18/R...

Major features:
* lld as the default linker on x86_64-unknown-linux-gnu
* cargo workspace publishing support built into cargo
* more const context APIs, and stabilization of new useful APIs
Announcing Rust 1.90.0 | Rust Blog
Empowering everyone to build reliable and efficient software.
blog.rust-lang.org
September 18, 2025 at 2:17 PM
Reposted by Stefan Holderbach
Exciting to see our protein binder design pipeline BindCraft published in its final form in @Nature ! This has been an amazing collaborative effort with Lennart, Christian, @sokrypton.org, Bruno and many other amazing lab members and collaborators.

www.nature.com/articles/s41...
August 27, 2025 at 4:14 PM
Reposted by Stefan Holderbach
overheard, with regards to nushell "That is pretty cool that you can just do that kind of stuff with the shell scripting. " 🩵
August 26, 2025 at 4:24 AM
Reposted by Stefan Holderbach
Publication alert: Our paper on domain insertion predictions in proteins is now out in @natmethods.nature.com in its final form: rdcu.be/ey7w3
Also check out the nice perspective by @noahholzleitner.bsky.social and @grunewald.bsky.social : www.nature.com/articles/s41...
Rational engineering of allosteric protein switches by in silico prediction of domain insertion sites
Nature Methods - ProDomino is a machine leaning-based method, trained on a semisynthetic domain insertion dataset, to guide the engineering of protein domain recombination.
rdcu.be
August 4, 2025 at 12:28 PM
Reposted by Stefan Holderbach
Excited to share work with
Zhidian Zhang, @milot.bsky.social, @martinsteinegger.bsky.social, and @sokrypton.org
biorxiv.org/content/10.1...
TLDR: We introduce MSA Pairformer, a 111M parameter protein language model that challenges the scaling paradigm in self-supervised protein language modeling🧵
Scaling down protein language modeling with MSA Pairformer
Recent efforts in protein language modeling have focused on scaling single-sequence models and their training data, requiring vast compute resources that limit accessibility. Although models that use ...
biorxiv.org
August 5, 2025 at 6:31 AM
Reposted by Stefan Holderbach
MMseqs2 v18 is out
- SIMD FW/BW alignment (preprint soon!)
- Sub. Mat. λ calculator by Eric Dawson
- Faster ARM SW by Alexander Nesterovskiy
- MSA-Pairformer’s proximity-based pairing for multimer prediction (www.biorxiv.org/content/10.1...; avail. in ColabFold API)
💾 github.com/soedinglab/M... & 🐍
August 5, 2025 at 8:25 AM
Reposted by Stefan Holderbach
Our paper benchmarking foundation models for perturbation effect prediction is finally published 🎉🥳🎉

www.nature.com/articles/s41...

We show that none of the available* models outperform simple linear baselines. Since the original preprint, we added more methods, metrics, and prettier figures!

🧵
August 4, 2025 at 1:52 PM
Reposted by Stefan Holderbach
Our work on rationally engineering allosteric protein switches is now out in Nature Methods: www.nature.com/articles/s41... Thanks a lot to @grunewald.bsky.social and @noahholzleitner.bsky.social for the comprehensive news and views: www.nature.com/articles/s41...
Rational engineering of allosteric protein switches by in silico prediction of domain insertion sites - Nature Methods
ProDomino is a machine leaning-based method, trained on a semisynthetic domain insertion dataset, to guide the engineering of protein domain recombination.
www.nature.com
August 4, 2025 at 11:41 AM
Reposted by Stefan Holderbach
I talk a lot about Rust for building high-perf (& even non-perf critical) software, & scientific software in particular. I often discuss what's interesting to me, but wanted to offer the chance to those interested for me to answer their questions about Rust in science. Fire away with questions!🧬🖥️
August 3, 2025 at 6:12 PM
Absolutely spoiled by match and if/else being expressions in Rust and Nushell. Really feels pedestrian trying to achieve the same in Typescript or Python.

(No the ternary operator is not "control flow as expressions" we have at home)
July 9, 2025 at 7:08 PM
Reposted by Stefan Holderbach
#AwesomeTools 1: uv docs.astral.sh/uv/ has transformed how I work with Python projects locally and for development and distribution. No more pip, venv, poetry, etc. seamless package management, virtual environments, development and deployment deliverer FAST & without hassle!
uv
uv is an extremely fast Python package and project manager, written in Rust.
docs.astral.sh
July 8, 2025 at 1:16 PM
Reposted by Stefan Holderbach
Rust 1.88.0 has been released! ✨🎊 🦀

This release brings you let chains, naked functions, automatic Cargo cache cleaning, Cell::update, proc_macro span locations, as_chunks methods on slices, and more!

Check out the blog post and release notes for all the details: blog.rust-lang.org/2025/06/26/R...
Announcing Rust 1.88.0 | Rust Blog
Empowering everyone to build reliable and efficient software.
blog.rust-lang.org
June 27, 2025 at 10:50 AM
Reposted by Stefan Holderbach
Excited to share my main PhD work is finally out! 🥳

We built a phage-assisted evolution platform to evolve allosteric protein switches (POGO-PANCE) and introduce cumulative, targeted mutations/Indels (RAMPhaGE)!

See how we evolved ultra-strong, light-switchable AraC variants 🌚🌞
June 13, 2025 at 9:23 AM
Reposted by Stefan Holderbach
I started tgv to learn Rust and building it has been unbelievably fun! If you wanna pick up a super fast and fun programming language, tgv is open for contribution! There aren't many bioinformatics tools built entirely by the community. If tgv can become one, I'll be so psyched
Terminal Genome Viewer (tgv), written in Rust github.com/zeqianli/tgv
May 28, 2025 at 5:57 AM
Reposted by Stefan Holderbach
New paper alert! We introduce the modular allosteric thermo-control of protein activity. Employing the AsLOV2 domain and mutants thereof as thermoreceptors, we engineered diverse hybrid proteins, whose activity can be controlled by small temperature changes (37-40/41 °C).

doi.org/10.1101/2025...
doi.org
May 3, 2025 at 11:03 AM
Reposted by Stefan Holderbach
Nushell 0.104 is out: www.nushell.sh/blog/2025-04...

gh's @cosineblast continues to iterate on job support, with experimental support for message passing between jobs
April 30, 2025 at 4:23 PM
Reposted by Stefan Holderbach
AFESM: a metagenomic guide through the protein structure universe! We clustered 821M structures (AFDB&ESMatlas) into 5.12M groups; revealing biome-specific groups, only 1 new fold even after AlphaFold2 re-prediction & many novel domain combos. 🧵
🌐 afesm.foldseek.com
📄 www.biorxiv.org/content/10.1...
April 27, 2025 at 12:13 AM
Reposted by Stefan Holderbach
terminal escape codes

wizardzines.com/comics/escap...
April 29, 2025 at 3:10 PM
Reposted by Stefan Holderbach
"If you're used to being able to sit down and bang out code, any time, anywhere, with all kinds of tools (libraries, compilers, virtual machines, what have you) at your fingertips, then yeah, working up a new assay protocol in a cell line is going to seem agonizingly slow" (from 2015)
April 21, 2025 at 7:45 AM
Reposted by Stefan Holderbach
We have an exciting new PhD opportunity!

If you are fsacinated by proteins and their dynamics and want to engineer them to develop new molecular tools: apply now!
We are a young and dynamic team combining state-of-the-art laboratory and bioinformatics approaches.
Please share.
April 1, 2025 at 11:52 AM
The state of academic funding in 2025!!!
The "empty space in plots could be used for advertisements" April Fools paper got me to literally laugh out loud 🔭🧪

arxiv.org/pdf/2503.24254
April 1, 2025 at 5:27 PM
Reposted by Stefan Holderbach
Labeling your axes and then explaining them slowly is perhaps the biggest bang for the buck you can get for making your slides more understandable.
March 12, 2025 at 4:38 PM
Using Rust
for Bioinformatics
tackling the complexity of VCF
with a common scripting language (lua)

Color me intrigued!
github.com/brentp/vcfex...
March 6, 2025 at 5:27 PM