Caleb Lareau

Caleb Lareau

@caleblareau.bsky.social

assistant professor @mskcancercenter.bsky.social clareaulab.com

1.2K followers468 following78 posts

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It's cool to see we aren't the only ones that think rationally designed probes + gapfilling is the future. Check out a corroborating workflow from @mgrillo.bsky.social, @lgmartelotto.bsky.social, Anna Nam, and colleagues: bsky.app/profile/mgri... 7/n

Marco Grillo@mgrillo.bsky.social

Capturing somatic mutations in single-cell probe-based assays (ie. 10X Flex) is a hard task, especially if you don't know *exactly* the mutations you want to capture, or if your target sequence is a mutational hotspot with many possible alternative alleles. Here's the way we pulled this off. Enjoy!

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3. This design enables genotyping hundreds of loci in individual cells at an accuracy much higher than other workflows for genotyping off of flex. GIFT simply works incredibly well. 5/n

I lied-- here's a fourth thing you should know. GIFT is fully loaded and ready to go in your lab. > The experimental protocol is fully open-sourced. > We have 3 git repos for probe design, parsing, and downstream analyses > We've validated it in primary samples and preserved FFPE tissues 6/n

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The three things you need to know: 1. GIFT uses short DNA probes to enable genotyping anywhere in a transcript and reads out potential mutations with a short 'gapfilling' reaction between adjacent probes. 3/n

2. GIFT builds on the 10x Genomics Flex kit, enabling a multi-step combinatorial barcoding that scales cell capture for genotype-to-phenotype mapping by ~an order of magnitude. 4/n

Caleb Lareau reposted

Caleb Lareau reposted

I defended my PhD 10 years ago today. That was the least remarkable thing that happened that day. Sharing something I wrote about it last year. Since then "the horrors persist but so do we." And with dignity.

Caleb Lareau reposted

Re-analysis of human population-scale whole genome seq data elucidates genetic architecture of EBV DNA persistence, a framework for the broader human virome @nature.com @caleblareau.bsky.social @sherrynyeo.bsky.social @erinmayc.bsky.social @ryandhindsa.bsky.social www.nature.com/articles/s41...

Caleb Lareau@caleblareau.bsky.social

Today in @nature.com, we describe how discarded reads in biobank-scale WGS can help resolve the genetic predictors and consequences of Epstein-Barr Virus (EBV) infection. Wonderful working with @ryandhindsa.bsky.social @sherrynyeo.bsky.social @erinmayc.bsky.social www.nature.com/articles/s41...

Caleb Lareau reposted

This was a fun and rewarding collaboration! A great example of extracting biological signal from data hiding in plain sight

Caleb Lareau@caleblareau.bsky.social

Today in @nature.com, we describe how discarded reads in biobank-scale WGS can help resolve the genetic predictors and consequences of Epstein-Barr Virus (EBV) infection. Wonderful working with @ryandhindsa.bsky.social @sherrynyeo.bsky.social @erinmayc.bsky.social www.nature.com/articles/s41...

Our prior thread digesting this work is available here. The key findings are the same from the preprint, but there's a boatload of new analyses for corroboration and interpretation of this new biomarker. bsky.app/profile/cale...

Caleb Lareau@caleblareau.bsky.social

Excited to share a new preprint from the lab with @ryandhindsa.bsky.social ! www.biorxiv.org/content/10.1... Led by @sherrynyeo.bsky.social, @erinmayc.bsky.social, and friends, we continue our journey to find viral DNA in our favorite place-- the overlooked and discarded reads in existing data! 1/

Caleb Lareau reposted

Caleb Lareau reposted

i see this all the time with no mention of structural suppression: - Electoral College winner-take-all - working day elections - voter registration burden turnout in battleground states is fairly high. people aren't lazy. they are responding to disincentivization and disenfranchisement.

Ashlie Weeks, Esq.--"Mo"@ashlieweeks.bsky.social

Close to 90 million people did NOT vote in the 2024 election. 90 million. It bears repeating over and over and over.

Caleb Lareau reposted

Caleb Lareau reposted

How can mitophagy be an effective quality control mechanism if mtDNA mutations reach high enough levels to cause disease? This question led us into a dark path, full of concepts of evolutionary genetics, germline stem cell biology and mito-nuclear compatibility. www.science.org/doi/10.1126/...

science.orgUbiquitin-mediated mitophagy regulates the inheritance of mitochondrial DNA mutationsMitochondrial synthesis of adenosine triphosphate is essential for eukaryotic life but is dependent on the cooperation of two genomes: nuclear and mitochondrial DNA (mtDNA). mtDNA mutates ~15 times as...

Caleb Lareau reposted

Two group leader positions available in the broader areas of RNA science, RNA technologies, and RNA medicine. Attractive packages and a great environment. Come and join us at Helmholtz RNA Würzburg, Bavaria.

Caleb Lareau reposted

We’re excited to report work led by postdoc Jennifer Porat in the lab, finding that DNA accumulates on the surface of living cells and that the secreted extracellular protein DNASE1L3 can modulate its levels on B and T cells. With a new twist for ATAC-seq as well www.biorxiv.org/content/10.1...

biorxiv.orgDNASE1L3 surveils mitochondrial DNA on the surface of distinct mammalian cellsThe extracellular space is a critical environment for discriminating self versus non-self nucleic acids and initiating the appropriate immune responses through signaling cascades to relay information ...

Caleb Lareau reposted

A new Nature Medicine study analyzing health records from >100 million people in the US offers compelling evidence that reactivation of varicella-zoster virus (VZV) ,the same virus that causes chickenpox and shingles may contribute to dementia risk. www.nature.com/articles/s41...

nature.comVaricella-zoster virus reactivation and the risk of dementia - Nature MedicineLarge-scale longitudinal health records reveal consistent association of varicella-zoster virus reactivation with dementia.

Caleb Lareau reposted

BREAKING: The Nobel Prize in Physiology or Medicine has been awarded jointly to Mary E. Brunkow, Fred Ramsdell, and Shimon Sakaguchi "for their discoveries concerning peripheral immune tolerance" Stay tuned for more. #NobelPrize

Caleb Lareau reposted

Caleb Lareau reposted

Does anyone have a good, reasonably up-to-date review of cryo-EM uses and methodology for (relatively) high-resolution protein structure determination? For someone who doesn't have a cryo-EM background.

Caleb Lareau reposted