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Stephan Köstlbacher @stephkoe.bsky.social · Aug 22

#MicroSky #mevoSky

Lorenzo Olivi @loreoliv.bsky.social · Aug 22

🧵 Our study on the elusive titration control mechanism of the replication initiator DnaA in Escherichia coli is now out on @natcomms.nature.com‬! @stephkoe.bsky.social
@hohlbeinlab.bsky.social‬ @nicoc-micsynmet.bsky.social @ettema.bsky.social‬ @mib-wur.bsky.social
doi.org/10.1038/s414...

The Escherichia coli replication initiator DnaA is titrated on the chromosome - Nature Communications

A DNA-binding protein, DnaA, regulates the initiation of chromosomal replication in bacteria. Here, Olivi et al. show that the bacterial chromosome sequesters DnaA in a growth rate-dependent manner, s...

doi.org

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Stephan Köstlbacher @stephkoe.bsky.social · Aug 22

If you want to mess around with some motifs, check out:
github.com/stephkoest/E...

GitHub - stephkoest/Ecoli_titration

Contribute to stephkoest/Ecoli_titration development by creating an account on GitHub.

github.com

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Stephan Köstlbacher @stephkoe.bsky.social · Aug 22

Never thought I’d do real E. coli research, so far I used if only for cloning & protist snacks in my MSc 😅

But here I am simulating chromosomes & shuffling motifs.

Watching @loreoliv.bsky.social and the lab turn those predictions into real data was pure magic.✨

Grateful to be part of this team!

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Reposted by Stephan Köstlbacher

Martin Steinegger 🇺🇦 @martinsteinegger.bsky.social · Jul 7

Folddisco finds similar (dis)continuous 3D motifs in large protein structure databases. Its efficient index enables fast uncharacterized active site annotation, protein conformational state analysis and PPI interface comparison. 1/9🧶🧬
📄 www.biorxiv.org/content/10.1...
🌐 search.foldseek.com/folddisco

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Stephan Köstlbacher @stephkoe.bsky.social · Jul 28

It was a pleasure to work with you! 😊

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Stephan Köstlbacher @stephkoe.bsky.social · Jul 21

Hey Felix, good question! Yeah it is different. In short: trimAl/ClipKit aim to remove uninformative sites. WitChi is a second step to remove misleading sites: those that can group unrelated taxa just because their sequence composition looks similar. Hope that helps!

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Reposted by Stephan Köstlbacher

Asaf Levy @asaflevylab.bsky.social · Jul 21

📢 New preprint alert!
We used comparative genomics on 72,000+ bacterial genomes to uncover the genetic basis of microbial adaptation to multicellular hosts—plants and animals alike.
www.biorxiv.org/content/10.1...

The Genetic Basis of Bacterial Adaptation to Hosts

Microbes colonize and interact with diverse multicellular hosts using specialized genes, many of which remain unidentified. Better understanding of host-associated gene functions is a key aspect of mi...

www.biorxiv.org

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Stephan Köstlbacher @stephkoe.bsky.social · Jul 21

Thanks, jolien! ;)

Stephan Köstlbacher @stephkoe.bsky.social · Jul 20

And of course the great work!

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Stephan Köstlbacher @stephkoe.bsky.social · Jul 20

Thanks for that beautiful summary, kassi :)

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Reposted by Stephan Köstlbacher

Kassiani Panagiotou @kassipan.bsky.social · Jul 20

Excited to share our work on WitChi! 🛠️🖥️
We tested it on the GTDB r220 archaeal supermatrix (5,869 taxa & 10,101 cols) removing 55% of sites in <2h.

The phylogeny showed several interesting groupings with overall improved branch support:
#phylogenetics #ArchaeaSky #MSA #opensource #MEvoSky #MicroSky

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Reposted by Stephan Köstlbacher

Daan Speth @daanspeth.bsky.social · Jun 10

I'm happy to announce the latest release of the GlobDB, available at globdb.org.

The GlobDB is a database of "species dereplicated" microbial genomes, and as of release 226 contains twice the number of species-representative genomes (306,260) than the latest GTDB release.

home | GlobDB

globdb.org

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Stephan Köstlbacher @stephkoe.bsky.social · Jul 20

It was a fun project :) Thanks for the support!

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Stephan Köstlbacher @stephkoe.bsky.social · Jul 20

9. TL;DR + link dump
WitChi is:
✔ Fast
✔ Interpretable
✔ Tree- and model-free
✔ Benchmark-validated
Designed to fix compositional bias at phylogenomic scale.
With: @kassipan.bsky.social, @danieltamarit.bsky.social, @ettema.bsky.social
💻 github.com/stephkoest/w...
📄 www.biorxiv.org/content/10.1...

GitHub - stephkoest/witchi: A compositional bias testing and pruning tool for multiple sequence alignments

A compositional bias testing and pruning tool for multiple sequence alignments - stephkoest/witchi

github.com

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Stephan Köstlbacher @stephkoe.bsky.social · Jul 20

8.
GTDB r220 case study (led by @kassipan.bsky.social )
Applied WitChi to the archaeal GTDB r220 supermatrix:
• 5,869 taxa
• 55% of columns pruned
• Biased taxa: 95.1% → 2.3%
• Runtime: <2h on 4 cores
→ Known clades recovered — without using very complex C60 or CAT models

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Stephan Köstlbacher @stephkoe.bsky.social · Jul 20

7.
Use witchi test to quantify bias per taxon:
• χ² scores
• Empirical p-values (via permutations)
• Z-scores to see how far taxa deviate from expectation
→ Great for screening MSAs or comparing compositional distortion across datasets.

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Stephan Köstlbacher @stephkoe.bsky.social · Jul 20

6.
WitChi solves both problems:
🔹 Builds a null distribution using column permutations — no model, no tree
🔹 Recursively removes columns that distort the taxon-wise χ² profile
🎁 Bonus: 3 scoring strategies, including one capturing distribution-wide effects (Wasserstein)
⚡ Scales linearly with taxa

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Stephan Köstlbacher @stephkoe.bsky.social · Jul 20

5.
Classical χ² pruning trims biased columns once — fast, but naive.
→ As alignment composition shifts, Δχ² must be updated — few tools do this.
BMGE’s stationary-based algorithm prunes iteratively and works well, but scales quadratically with taxa — not feasible for medium sized or large datasets.

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Stephan Köstlbacher @stephkoe.bsky.social · Jul 20

4.
The problem:
χ² assumes taxa are independent and identically distributed samples.

In MSAs, they share history → correlated data.
So parametric χ² nulls are invalid.
Simulations help, but they need known models and trees — which bias distorts.
→ Slow, circular, rarely used.

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Stephan Köstlbacher @stephkoe.bsky.social · Jul 20

3.
We often use χ² stats to detect bias — how much a taxon’s sequence composition deviates from expectation.
χ² pruning removes columns with strong bias signal.
But both steps rely on assumptions that don’t hold in real MSAs.

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Stephan Köstlbacher @stephkoe.bsky.social · Jul 20

2.
What’s compositional bias?
When unrelated taxa convergently evolve similar sequence compositions (e.g. GC-rich, AT-rich), tree algorithms may group them by chemistry, not ancestry — a well-known artefact in deep phylogenies.
Fig modified from: doi.org/10.1007/978-...

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Stephan Köstlbacher @stephkoe.bsky.social · Jul 20

1.
🧵 New preprint out!
WitChi: a fast, open-source Python tool to detect, quantify & prune compositional bias in MSAs.
Lightweight, tree-free, scalable to 5k+ taxa... so we applied it to the GTDB archaea MSA.
#ArchaeaSky #MEvoSky #MicroSky
🔗 doi.org/10.1101/2025...
💻 github.com/stephkoest/w...

WitChi: Efficient Detection and Pruning of Compositional Bias in Phylogenomic Alignments Using Empirical Chi-Squared Testing

Convergent evolution, where unrelated taxa independently evolve similar nucleotide or amino acid compositions, can introduce compositional bias into biological sequence data. Such biases distort phylo...

www.biorxiv.org

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Reposted by Stephan Köstlbacher

cemess_vienna @cemess.bsky.social · Jul 8

Exciting new research! Matthias Horn & Lukas Helmlinger from #CeMESS uncover how chlamydiae thrive in social amoebae by skipping their extracellular stage.

Read their groundbreaking study in Current Biology (@currentbiology.bsky.social):

🔗 cemess.univie.ac.at/news/detail-...

New Paper: Chlamydiae give up extracellular stage to thrive in social amoebae

Many intracellular bacteria rely on an extracellular stage to move between hosts – but what happens when that’s no longer needed? A new study, now published in Current Biology, reveals a striking exam...

cemess.univie.ac.at

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Reposted by Stephan Köstlbacher

Lukas Helmlinger @helm-linger.bsky.social · Jul 9

Excited to share our first paper on the symbiosis between chlamydiae and social amoebae showing in detail the adaptations of endosymbionts to the social life style of their host! 🎉

cemess_vienna @cemess.bsky.social · Jul 8

Exciting new research! Matthias Horn & Lukas Helmlinger from #CeMESS uncover how chlamydiae thrive in social amoebae by skipping their extracellular stage.

Read their groundbreaking study in Current Biology (@currentbiology.bsky.social):

🔗 cemess.univie.ac.at/news/detail-...

New Paper: Chlamydiae give up extracellular stage to thrive in social amoebae

Many intracellular bacteria rely on an extracellular stage to move between hosts – but what happens when that’s no longer needed? A new study, now published in Current Biology, reveals a striking exam...

cemess.univie.ac.at

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Reposted by Stephan Köstlbacher

STCmicrobeblog @stcmicrobeblog.bsky.social · Jun 22

a midsummer night's dream
or
understanding chromosome organization's deep evolutionary roots
#MicroSky #Archaea #ArchaeaSky #ProtistsOnSky et al.

borrowed from https://www.rsc.org.uk/a-midsummer-nights-dream/production-photos

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