Experimental demonstrations of ensemble epistasis: mutations interacting by modulating the distribution of conformational states in an ensemble. Cool!

Check out our new preprint (led by Mike Pun University of Washington) on 3D rotationally equivariant model of protein structure micro-environments, with a holographic CNN (H-CNN): doi.org/10.1101/2022.1…

Looking forward to Sebastian Prillo’s talk tomorrow morning 🍿

TIL: postdocs are “part-time” workers? And doing “professionally relevant” research work is itself a form of “support” postdocs are *receiving from* UC, rather than providing to it? 🤨

I had some snow-related airport delays in Seattle last week, but am very thankful for the chance to sneak in a cheeky powder day. So fun! 📷 by David Bacsik

Interested in a fast, accurate method for estimating the parameters of a complex phylogenetic model of molecular evolution (e.g. a general rate matrix describing the co-evolution of protein contact sites in 3D)? If so, please check out our preprint: doi.org/10.1101/2022.1… (1/10)

Really happy to see this paper is out! It’s the brainchild of our dear postdoc Jonatan Ersching, who passed away in 2020. It’s not only a science story, but also the story of how we came together as a lab to finish what Jony started. cell.com/cell/fulltext/…

Andrew Kern and I are organizing a symposium at #SMBE23 on machine learning and evolutionary genomics. We are delighted to have Yun S. Song and Sohini Ramachandran as our invited speakers. Should be a blast! Abstract submissions are due on March 15. We hope to see you in Ferrara!

Recently Richard Wang Matthew Hahn et al inferred past human generation times from changes in the mutation spectrum over time. We think this approach is heavily biased by uncertainties in allele age and de novo mutation rate estimates. See biorxiv.org/content/10.110… and below:

Deeply concerning to see that the model and data are so inconsistent in Wang et al.

Thrilled about this publication (with a beautiful cover image) from a collaboration with the Tishkoff lab, which started 6 years ago! The article is freely available at the following link for 50 days: authors.elsevier.com/c/1ggtbL7PXmbco

Last year, a team led by @tomsasani and I found that germline mutation rates and spectra differ between C57BL/6 and DBA/2J lab mice. We mapped the C>A mutator phenotype to the DNA repair gene Mutyh. Now with Aaron Quinlan we show there's more to the story! biorxiv.org/content/10.110…

Very exciting news, Pengyao!!! I look forward to seeing all kinds of great science from you and your trainees, and encourage any potential trainees interested in molecular mechanisms of evolution to head your way.

We've developed new machinery to quickly compute likelihoods under the discrete-time Wright Fisher model, motivated by estimating selection from exomes. We also looked at how much info can be gained by sequencing more exomes (spoiler: not much!) doi.org/10.1101/2023.0… 🧵👇

We think the mutation spectrum is evolving b/c it tends to cluster by population and species. Now in a study led by Annabel Beichman, we measure the mutation spectrum’s phylogenetic signal across 100 million years of mammalian evolution biorxiv.org/cgi/content/sh…

Very glad to see our CherryML method published online in Nature Methods. The published version has updated and expanded results, so please check it out. doi.org/10.1038/s41592… (1/3)

Today out in Nature Reviews Genetics: our review on how evolutionary control should be devised to improve synthetic biology, molecular design, and drug and vaccine design against pathogens. with Michael Lässig, & Ville Mustonen nature.com/articles/s4157…

We're hiring! Please pass this announcement on to people who like thinking about genealogical trees, genomic data, and/or data structures! (And, contact me by email or on 🐘, probably not here.)