Tetsuya Yamada

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
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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.

Now published @natecoevo.nature.com with @annika-nichols.bsky.social, our latest on the evolution of 𝘴𝘭𝘦𝘦𝘱 across 𝟲𝟬 𝘀𝗽𝗲𝗰𝗶𝗲𝘀 of cichlid fishes! doi.org/10.1038/s415...
with members of the @schierlab.bsky.social and Salzburger labs, as well as the burgeoning Shafer lab @uoftcellsysbiol.bsky.social

The evolution of hominin bipedalism in two steps - Nature The human pelvis exhibits distinct spatiotemporal ossification patterns and an ilium cartilage growth plate that is shifted perpendicularly compared with those of other mammals and non-human primates—...

1) I am delighted to present this terrific tour de force research conducted by my post-doc Dr. Gayani Senevirathne @gayani.bsky.social and published today in Nature -
www.nature.com/articles/s41...

In the genomics community, we have focused pretty heavily on achieving state-of-the-art predictive performance.

While undoubtedly important, how we *use* these models after training is potentially even more important.

tangermeme v1.0.0 is out now. Hope you find it useful!

Evolution of Cajal-Retzius Cells in Vertebrates from an Ancient Class of Tp73+ Neurons In the developing cerebral cortex, Cajal Retzius (CR) cells are early-born neurons that orchestrate the development of mammalian-specific cortical features. However, this cell type has not been conclu...

Excited to share our latest work on brain evolution, where we dive into the evolution of Cajal-Retzius cells! If you are interested in cell type evolution and cerebral cortex evo-devo, please read on… www.biorxiv.org/content/10.1... 🧵 1/7

Activity of most genes is controlled by multiple enhancers, but is there activation coordinated? We leveraged Nanopore to identify a specific set of elements that are simultaneously accessible on the same DNA molecules and are coordinated in their activation. www.biorxiv.org/content/10.1...

Please RP.
We are thrilled to announce that our lab’s first preprint is out!
”Whole-genome single-cell multimodal history tracing to reveal cell identity transition”

We report HisTrac-seq, a multiomic single-cell molecular recording platform.
www.biorxiv.org/content/10.1...

A busy tool wall in a shed. At the bottom there are instructions saying "Find the 10 hidden enhancers!" Across the wall between the tools are 10 enhancers, represented as DNA helices, but they are difficult to find in the style of a "hidden object" puzzle. Original photo by Lachlan Donald, https://www.flickr.com/photos/lox/9408028555

Hiding in plain sight - how close are we to mapping ALL 🧬enhancers🧬 in the genome?

Our new paper by Mannion et al. takes a systematic look at "hidden enhancers" and why they remain so hard to find. With @mosterwalder.bsky.social, @jlopezrios.bsky.social & many more

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

Excited to see this published with additional data following our preprint a while back. Cool combination (in our biased view) of controlled TF expression and machine learning to decode chromatin sensitivity. www.sciencedirect.com/science/arti....

Three major trends in comparative transcriptomics

🧬🧬🧬 New review from the lab:

Evolution of comparative transcriptomics: biological scales, phylogenetic spans, and modeling frameworks

authors.elsevier.com/sd/article/S...

By @mattezambon.bsky.social & @fedemantica.bsky.social, together with @jonnyfrazer.bsky.social & Mafalda Dias.

Beeswarm plot of the prediction error across different methods of double perturbations showing that all methods (scGPT, scFoundation, UCE, scBERT, Geneformer, GEARS, and CPA) perform worse than the additive baseline.

Line plot of the true positive rate against the false discovery proportion showing that none of the methods is better at finding non additive interactions than simply predicting no change.

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!

🧵

You link #phenotype 🦜 to #genotype 🧬 with #comparative #genomics 💻?

This #review is for you 📜: authors.elsevier.com/sd/article/S...

We review new #methods, remaining #challenges and #future directions and highlight recent key studies.

Thanks @hillermich.bsky.social!

Please share! 🙂

Under which circumstances do genomic neural networks learn motifs and their interactions? The use of neural networks to model genomic data in sequence-to-function scenarios has soared over the last decade. There remains much debate about whether these models are interpretable, either inher...

Under which circumstances do genomic neural networks learn motifs and their interactions?https://www.biorxiv.org/content/10.1101/2025.07.25.666754v1

Marsupial single-cell transcriptomics identifies temporal diversity in mammalian developmental programs Menchero et al. generate a single-cell transcriptomic atlas in the opossum and show rapid progression of transcriptional programs in specific tissues relative to morphological landmarks. This shift in...

Thrilled to share that our latest work on marsupial heterochrony is now online at @cp-devcell.bsky.social @cellpress.bsky.social @lab-turner.bsky.social @crick.ac.uk We used scRNAseq to understand the asynchronous progression of developmental programmes in marsupials www.cell.com/developmenta...

Diet/microbes place the gut epithelium as a nexus for evolutionary change. With Jason Spence and Craig Lowe labs we use #organoids to explore how evolution prepared the developing human intestine for exposure to the environment. @science.org #evodevo www.science.org/doi/10.1126/... 1/11

Borzoi-informed fine mapping improves causal variant prioritization in complex trait GWAS Genome-wide association studies (GWAS) have identified thousands of trait-associated loci. Prioritizing causal variants within these loci is critical for characterizing trait biology. Statistical fine...

I'm excited to share work on a research direction my team has been advancing: connecting machine learning derived genetic variant embeddings to downstream tasks in human genetics. This work was led by the amazing Divyanshi Srivastava! www.biorxiv.org/content/10.1...

A phylogenetic approach uncovers cryptic endogenous retrovirus subfamilies in the primate lineage A phylogenetic approach reveals cryptic LTR subfamilies and functional insights at nucleotide resolution in primates.

Is the annotation of viruses in the human genome accurate? We think not. Take a look at our new paper and let us know if you agree! www.science.org/doi/10.1126/...

Check out our latest work co-led by @dcsoto.bsky.social and @jmuribescr.bsky.social identifying hundreds of human duplicated gene families using the new T2T-CHM13 assembly, with a focus on those potentially contributing to brain evolution 🧪: authors.elsevier.com/a/1lTQtL7PXu...

Thrilled to see our revised preprint now published in Nature Ecology & Evolution!
If you’re curious about how to build a bat wing by re-using existing gene programs, check out the link or the tutorial below. Big congratulations to all co-authors!! Thanks to reviewers!

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

A male-essential miRNA is key for avian sex chromosome dosage compensation - Nature Birds have evolved a unique sex chromosome dosage compensation mechanism involving the male-biased microRNA (miR-2954), which is essential for male survival by regulating the expression of dosage-sens...

Our study on a male-essential microRNA and the evolution of other dosage compensation mechanisms in birds is now out in Nature! www.nature.com/articles/s41...

My postdoc work at Treutlein lab and @graycamplab.bsky.social with @jasperjanssens.bsky.social is out in @science.org ! We screen for neuron subtypes using pro-neural TFs + morphogen combinations + scRNA-seq and profiled over 700,000 cells in 480 conditions. www.science.org/doi/10.1126/...