Tetsuya Yamada

Causal modelling of gene effects from regulators to programs to traits - Nature Approaches combining genetic association and Perturb-seq data that link genetic variants to functional programs to traits are described.

GWAS has been an incredible discovery tool for human genetics: it regularly identifies *causal* links from 1000s of SNPs to any given trait. But mechanistic interpretation is usually difficult.

Our latest work on causal models for this is out yesterday:
www.nature.com/articles/s41...
A short🧵:

Programmatic design and editing of cis-regulatory elements The development of modern genome editing and DNA synthesis has enabled researchers to edit DNA sequences with high precision but has left unsolved the problem of designing these edits. We introduce Le...

After a huge amount of work w/ @alex-stark.bsky.social's group, a new version of our Ledidi preprint is now out!

In an era of AI-designed proteins, the next leap will be controlling when, where, and how much of these proteins are expressed in living cells.

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

Thank you Alex! Excited to see our paper published in @nature.com ! Huge thanks to @jeffspence.github.io , @tkyzeng.bsky.social , @emmamarydann.bsky.social, @nikhilmilind.dev, @marsonlab.bsky.social, @jkpritch.bsky.social, and all the members of the Pritchard and Marson labs for your enormous help!

New preprint from our lab, spearheaded by @maelledaunesse.bsky.social and in collaboration with Diego Villar!

In which we ask, can we detect joint signatures suggestive of positive selection on transcriptomes and epigenomes?

It was a pleasure meeting you. I really appreciated hearing about your work and enjoyed our conversation. Thank you for coming to Japan!

Happy to present TOGA2, developed by Yury Malovichko @ymalovichko.bsky.social, the faster, memory-efficient & more accurate TOGA1 successor (github.com/hillerlab/TO...). And annotations, orthologs & gene loss/dup data generated with 4 references for 883 placental mammal and with 5 refs for 676 ...

NEW pub in @science.org 🥳

Is it sponges (panels A & B) or comb jellies (C & D) that root the animal tree of life?

For over 15 years, #phylogenomic studies have been divided.

We provide new evidence suggesting that...

🔗: www.science.org/doi/10.1126/...

Excited to share Nona: a unifying multimodal masking framework for functional genomics.

Models for DNA have evolved along separate paths: sequence-to-function (AlphaGenome), language models (Evo2), and generative models (DDSM).

Can these be unified under a single paradigm? 1/15

Are you using any of our factor models, such as MOFA? 🛵
You might’ve found it challenging to tailor them to your specific use cases - not anymore!

Introducing MOFA-FLEX: a flexible, modular factor analysis framework designed for customizable modeling across diverse multi-omics data scenarios. 1/n

Our latest paper has just been published in Cell!

doi.org/10.1016/j.ce...

We developed a new method called MCC ultra, which allows 3D chromatin structure to be visualised with a 1 base pair pixel size.

Programming human cell type-specific gene expression via an atlas of AI-designed enhancers Differentially active enhancers are key drivers of cell type specific gene expression. Active enhancers are found in open chromatin, which can be mapped at genome scale across tissue and cell types. T...

🚀Excited to share our new preprint: “Programming human cell type-specific gene expression via an atlas of AI-designed enhancers”

We built the largest repository of AI-designed enhancers, validated across 10 human cell lines + mouse retina.

👉 www.biorxiv.org/content/10.1...

#AI #Genomics #SynBio

New preprint led by the brilliant @aleksandra-marconi.bsky.social on cichlid brain diversification, fgf8a signalling and regulatory divergence with TEs on the mix! All part of a wonderful collaboration with @ebablab.bsky.social

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

@camzoology.bsky.social

🧠🌟🐭 Excited to share some of my postdoc work on the evolution of dexterity!

We compared deer mice evolved in forest vs prairie habitats. We found that forest mice have:
(1) more corticospinal neurons (CSNs)
(2) better hand dexterity
(3) more dexterous climbing, which is linked to CSN number🧵

Thank you!

Thank you so much, Mari 😊 I’m also really looking forward to seeing all the amazing science coming from your lab!

So excited to see this out on bioRxiv! Huge thanks to @kaessmannlab.bsky.social and the amazing cerebellum team (@marisepp.bsky.social and @ioansarr.bsky.social) for all the support and insightful discussions that made this work possible!!

Excited to share the preprint from my main postdoc project! It’s been a long journey—huge thanks to everyone who made it possible, especially @leticiarm1618.bsky.social for being the best collaborator one could ask for, and the amazing @kaessmannlab.bsky.social lab for the invaluable support!

🧠 The Lipid #Brain Atlas is out now! If you think #lipids are boring and membranes are all the same, prepare to be surprised. Led by @lucafusarbassini.bsky.social with Giovanni D'Angelo's lab, we mapped membrane lipids in the mouse brain at high resolution.
www.biorxiv.org/cgi/content/...

We are thrilled to share our new preprint entitled “The origin and molecular evolution of the mammalian liver cell architecture” www.biorxiv.org/content/10.1...

Which mutations rewire function of regulatory DNA?

Excited to share SEAM: Systematic Explanation of Attribtuion-based Mechanisms. SEAM is an explainable AI method that dissects cis-regulatory mechanisms learned by seq2fun genomic deep learning models.

Led by @EESetiz

1/N 🧵👇

Sperm sequencing reveals extensive positive selection in the male germline - Nature A combination of whole-genome NanoSeq with deep whole-exome and targeted NanoSeq is used to accurately characterize mutation rates and genes under positive selection in sperm cells.

Now published! Our paper on:
(1) Accurate sequencing of sperm at scale
(2) Positive selection of spermatogenesis driver mutations across the exome
(3) Offspring disease risks from male reproductive aging
[1/n]
www.nature.com/articles/s41...

New preprint from the lab! We discovered a transient fluidization in the basal region of human forebrains by tracking microdroplets in cerebral organoids.This “basal fluidization”, absent in gorilla and mouse, may contribute to greater surface expansion in human forebrains
1/
doi.org/10.1101/2025...

Happy to share work spearheaded by former grad student Colin Shew testing shared duplicated cis regulatory elements (CREs) using an MPRA. While we find some high effect CREs, collectively paralog differences represent modest effects accounting for observed gene expression divergence.

A human-specific regulatory mechanism revealed in a pre-implantation model Nature - Genetic manipulation of blastoids reveals the role of recently emerged transposable elements and genes in human development.

Today in @nature.com, we present our work leveraging functional genomics and human blastoids to uncover a human-specific mechanism in preimplantation development driven by the endogenous retrovirus HERVK.
Special thanks to the reviewers whose comments improved our manuscript a lot! rdcu.be/eI3tD

New paper from my lab and @jshendure.bsky.social lab! Led by the brilliant @zukailiu.bsky.social and @cxqiu.bsky.social. We tackled how anterior and posterior progenitor cells cooperate to self-organize into an embryonic structure (termed AP-gastruloid). (1/n) www.biorxiv.org/content/10.1...

We are excited to share GPN-Star, a cost-effective, biologically grounded genomic language modeling framework that achieves state-of-the-art performance across a wide range of variant effect prediction tasks relevant to human genetics.
www.biorxiv.org/content/10.1...
(1/n)

bioRxiv - An unbiased survey of distal element-gene regulatory interactions with direct-capture targeted Perturb-seq

New preprint from our lab!

What can we learn about the properties of gene regulatory elements by CRISPR’ing a random set of accessible sites in human cells?

Find out here: www.biorxiv.org/content/10.1...

👇

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Cell-extrinsic controls over neocortical neuron fate and diversity Cell-extrinsic cues are key for neocortical cell identity and diversity.

Ever wondered how robust cellular identity is to external perturbations? Here we disrupt cellular environmnent in vivo and in vitro, and find cell population specific sensitivities. Environment sculpts development yes, but not all cells are made of the same wood. www.science.org/doi/10.1126/...

Species-specific Rates of Fatty Acid Metabolism Set the Scale of Temporal Patterning of Corticogenesis through Protein Acetylation Dynamics Developmental processes display temporal differences across species, leading to divergence in organ size and composition. In the cerebral cortex, neurons of diverse identities are generated sequential...

New from the lab: Fatty Acid Metabolism Sets the Species-specific Tempo of Cortical Development through Protein Acetylation Dynamics. Led by amazing trio: @ryo2iwata.bsky.social , Isabel Gallego, @emirerkol.bsky.social, together with @steinaerts.bsky.social , @fendtlab.bsky.social

🧠🦈Excited to present our latest work🧠🦈Interested in brain evolution? And shark embryos? Then read on… Our work sheds light on the deep origins of our brain’s most complex regions.