Wen-Wei Liao

I'm excited to share our pre-print about a new variant benchmarking tool we've been working on for the past few months!

Aardvark: Sifting through differences in a mound of variants
GitHub: github.com/PacificBiosc...

Some highlights in this thread:
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🦒Long read giraffe is out!🦒
Mapping long reads to pangenome graphs is ~10x faster than with GraphAligner, with veeery slightly better mapping accuracy, short variant calling, and SV genotyping than GraphAligner or Minimap2

Do you know ~60% of human SVs fall in ~1% of GRCh38? See our new preprint: arxiv.org/abs/2509.23057 and the companion blog post on how we started this project and longdust: lh3.github.io/2025/09/29/o.... Work with Alvin Qin

A complete diploid human genome benchmark for personalized genomics Human genome resequencing typically involves mapping reads to a reference genome to call variants; however, this approach suffers from both technical and reference biases, leaving many duplicated and ...

Delighted to finally announce a preprint describing the Q100 project! “A complete diploid human genome benchmark for personalized genomics” For which we finished HG002 to near-perfect accuracy: www.biorxiv.org/content/10.1... 🧵[1/14]

I'm hiring a computational biologist interested in complex trait genetics using deep learning approaches. Reach out to me, if interested.

Phishing site : minimap2.com · Issue #1316 · lh3/minimap2 Not sure how to label this one, but I have come across a website minimap2.com which appears to be AI generated but is serving it's own copy of the Github repository. If you search the address or em...

minimap2.com is potentially a phishing site. Please don't use anything from that website.
github.com/lh3/minimap2...

Now published in GigaScience with minor improvements: academic.oup.com/gigascience/...

* Download: zenodo.org/records/1490...
* More info: github.com/lh3/panmask

GitHub - jltsiren/gbz-base: Prototype for an immutable pangenome graph in SQLite Prototype for an immutable pangenome graph in SQLite - jltsiren/gbz-base

GBZ-base has been a side project for me for a couple of years. It's basically a GBZ graph stored in SQLite instead of a custom file format. You can convert a GBZ graph to GBZ-base quickly and then extract subgraphs around nodes / reference positions on a laptop. 1/n

Interesting job listings 👀 astromech.com

www.sec.gov/Archives/edg...

Postdoctoral Scholar – Genomics, Aging, Somatic Mutation, Structural Variation, Evolution , Cancer – Integrative Biology University of California, Berkeley is hiring. Apply now!

The Sudmant lab at UC Berkeley is seeking a postdoc to work on a fully funded NIH project to understand differences in DNA repair and somatic mutation across the primate tree of life. Please spread widely to those who may be interested aprecruit.berkeley.edu/JPF05052

Higher eQTL power reveals signals that boost GWAS colocalization Expression quantitative trait locus (eQTL) studies in human cohorts typically detect at least one regulatory signal per gene, and have been proposed as a way to explain mechanisms of genetic liability...

Good discussion & study-design recommendations in this new preprint by @mikelove.bsky.social @klmohlke.bsky.social & colleagues:
Higher eQTL power reveals signals that boost GWAS colocalization 🧪🧬

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

This sounds true to me

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!

🧵

Technical blogging for growth and learning Writing a technical blog improves your writing, forces you to learn new things, helps others and yourself, and helps your career. This post: why blog, what to blog about, how to start, and using AI.

Writing a technical blog improves your writing, forces you to learn new things, helps others and yourself, and helps your career. In this essay: (1) why blog, (2) what to blog about, (3) how to get started, and (4) using AI. https://doi.org/10.59350/bqnfd-7p249 🧪

65 Genomes Expand Our Picture Of Human Genetics Researchers closely examined the genomes of 65 individuals to paint a more complex, and more complete, picture of human genetic diversity.

Complete genomes alert! @glennislogsdon.bsky.social, @christinebeck.bsky.social, and I were on @scifri.bsky.social today talking about "Complex genetic variation in nearly complete human genomes"
📄 www.nature.com/articles/s41...
📻 www.sciencefriday.com/segments/65-...

GitHub - lh3/longdust: Identify long STRs, VNTRs, satellite DNA and other low-complexity regions in a genome Identify long STRs, VNTRs, satellite DNA and other low-complexity regions in a genome - lh3/longdust

Longdust, a new tool to identify highly repetitive STRs, VNTRs, satellite DNA and other low-complexity regions (LCRs). Similar to SDUST but for long regions.
github.com/lh3/longdust

Complex genetic variation in nearly complete human genomes - Nature Using sequencing and haplotype-resolved assembly of 65 diverse human genomes, complex regions including the major histocompatibility complex and centromeres are analysed.

Two papers in today's issue of @nature.com ‬: 1) we assemble 65 genomes to near completion, including centromeres and the MHC. tinyurl.com/3huhax6w. 2) we sequence 1,019 genomes from the 1kGP with long reads, revealing SVs down to low allele frequencies tinyurl.com/wbx3we9x.

Preprint on "Finding easy regions for short-read variant calling from pangenome data": arxiv.org/abs/2507.03718

This a really exciting leap forward for genomic sequence to activity gene regulation models. It is a genuine improvement over pretty much all SOTA models spanning a wide range of regulatory, transcriptional and post-transcriptional processes. 1/

Excited to launch our AlphaGenome API goo.gle/3ZPUeFX along with the preprint goo.gle/45AkUyc describing and evaluating our latest DNA sequence model powering the API. Looking forward to seeing how scientists use it! @googledeepmind

An assessment of DNA language models concludes:
◼️ They do not offer compelling gains over baseline models

Their performance is inconsistent and requires much more compute.

arxiv.org/abs/2412.05430

Reply to: Reply to: False positives in the study of memory-related gene expression In the Nature paper “Spatial transcriptomics reveal neuron–astrocyte synergy in long-term memory” published on March 14th, 2024, authors Sun et al. claimed to identify cell-type specifi…

I wrote a review of a recent paper on false discovery and multiple testing correction. liorpachter.wordpress.com/2025/06/16/r...

Preprint on "Improving spliced alignment by modeling splice sites with deep learning". It describes minisplice for modeling splice signals. Minimap2 and miniprot now optionally use the predicted scores to improve spliced alignment.
arxiv.org/abs/2506.12986

A blueprint for the batmobile.

Your genome is not a blueprint. A thread about misleading metaphors in science communication. 🧬🧪 1/n

People always stop me in the street to ask: "Yoav, where are the disease-associated eQLTs? We found a lot in GTEx but we can't find anymore. Do you know where they are?"

(For the record, no one has ever asked me this, but it is a really good question!)

I think we know where they are.

Standard methods are equivalent to a flashlight, looking at each gene independently. We combine signals from multiple genes, turning a floodlight onto the genome.

Excited to share my first PhD paper in the @sbmontgom.bsky.social lab with @tamigj.bsky.social (www.biorxiv.org/content/10.1...)! Standard QTL methods treat each gene independently. But what if a single variant regulates multiple nearby genes at once - what we call “allelic proxitropy”? 🧵 ⬇️

Very excited to share I’ll be starting my own group at University of Utah in the Department of Human Genetics in the new year! Reach out if you are interested! vollgerlab.com

Neng Huang developed longcallR for joint SNP calling and phasing from long RNA-seq reads, AND for identifying allele-specific splicing/junctions (ASJ). Although ASJs of statistical significance are rare, a large fraction involve unannotated junctions. In Rust!

The human pangenome continues to grow and improve! Release 2 is here! Click through for the details, but this is a pretty amazing dataset including not just the phased assemblies, but PacBio HiFi, ONT Ultralong, Dovetail/Illumina Hi-C, PacBio Kinnex, and Illumina WGS for all samples

Four images to illustrate some prominent single-gene myths. Top left shows a photograph of a person deftly rolling their tongue into a U-shape. Top right shows a photograph of a person’s ear, highlighting the shape and features of the earlobe and cartilage. Bottom left shows a close-up photograph of a person’s eye, with a vivid blue colouration. Bottom right shows a photograph of a person poised to write with their left hand on the blank white page of a spiral-bound notebook.

Remember when you first learned about genetics at school? All those fascinating examples of human traits that are each apparently determined by just a single gene? Time to check in on some of your favourites to see how they’re doing. 🧬🧵🧪 1/n