Josh Popp

Univariate-Guided Sparse Regression

We are excited to share the publication of our new paper "Univariate-guided sparse regression", with commentary by Larry Wasserman, Bin Yu, Lucas Janson, Cynthia Rudin and others.
hdsr.mitpress.mit.edu/pub/3i97j340...
Comments welcome!

Strober Lab The Strober lab is a computational group at Boston Children's Hospital (a Harvard Medical School affiliated hospital) focused on developing statistical and machine learning tools applied to human gene...

Exciting updates!!
(1) I just opened my lab at Boston Children’s Hospital (Harvard-affiliated)
(2) I’m hiring a postdoc focused on integrating GWAS and functional genomic data. Reach out if you’re interested or connect at ASHG next week!
(3) Learn more at stroberlab.com

I’ve spent a good chunk of my career relying on American science and engineering to keep me alive. Yesterday, RFK Jr. testified at the U.S. Senate Finance Committee. It was sad to see him try to destroy the life’s work of so many American scientists. He shouldn’t be in this job.

Exposure accumulation drives age-dependent disease architectures and polygenic risk scores Our understanding of the dependence of the genetic and environmental architecture of common diseases on age is incomplete. Here, we use longitudinal data to quantify age-dependent genetic and environm...

Excited to share our latest manuscript, "Exposure accumulation drives age-dependent disease architectures and polygenic risk scores," led by Xilin Jiang: www.medrxiv.org/content/10.1...

I am attempting an explainer thread for the first time here:
(I am usually too exhausted to post one)

A tweet "Elon Musk thinks our new embryo screening startup, @herasight, is "cool". Cool." with a picture included in the tweet of a web widget showing an embryo selected for IQ.

A quote tweet of Cremieux a pseud who "tweets about race & genetics" see here for more background on Cremieux/Lasker: https://www.theguardian.com/us-news/2025/mar/03/natal-conference-austin-texas-eugenics Text reads: "The widget pictured below gives you the expected range of predicted IQs (or disease risks) for the number of embryos. The difference between the average and the highest gives you the expected gain in IQ if you were selecting the embryo with the highest predicted IQ. "

The startup named Herasightm after the goddess who threw her disabled child off a mountain, seems focused on public outreach using embryo selection for IQ to win over far rightwing pseuds & techbros

Numerous FAQs & think pieces were written promising GWAS participants & the broader public that sociogenomics was focused on education improvement, environmental interventions, and away from the hereditarian past. All quickly betrayed.

Text from an FAQ in Okbay et al 20222: https://www.nature.com/articles/s41588-022-01016-z a similar same statement is made in an FAQ in 2025: https://www.biorxiv.org/content/10.1101/2025.05.14.653986v1.supplementary-material Text reads: "The results of SSGAC studies have sometimes been used by online platforms, including some companies, to predict individual outcomes. We recognize that returning individual genomic “results” can be a fun way to engage people in research and other projects and to feed or stoke their interest in genomics. But it is important that participants/users understand that these individual results are not meaningful predictions and should be regarded essentially as entertainment. Failure to make this point clear risks sowing confusion and undermining trust in genetics research"

It is depressing, but all too predictable, how swiftly we’ve gone from the Social Science Genetic Association Consortium offering reassurances about the uses of behavioural polygenic scores to one of their lead authors marketing embryo selection for IQ

First Patient Treated with Personalized CRISPR Therapy, Developed in Just Six Months The first on-demand CRISPR therapy for an infant with a rare metabolic disease developed by the IGI and collaborators around the world.

This is what can be achieved today due to longstanding federal support of academic basic science alongside close partnership of universities, private industry and NIH intramural initiatives. An ecosystem worth not just saving but doubling down on!

innovativegenomics.org/news/first-p...

1/n 🚨Very excited to share our recent work!🚨
To understand gene regulation across diverse environmental conditions and cellular contexts, we treated a broad array of human cell types with three environmental exposures in vitro.
www.biorxiv.org/content/10.1...

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

I keep coming back to this pithy 1854 statement by Abraham Lincoln about “the legitimate object of government,” which the Trump administration is undermining by offloading to individuals tasks, including life or death matters, that are more effectively, efficiently and fairly done collectively.

This framing is their framing, and NYT took the bait. The correct and accurate framing is: “Deep cuts to medical research threatens progress on cancer and heart disease research, costs the economy $80B, and threatens 300,000 jobs across red and blue states”

The website for the NIH Office of Research on Women's Health has nearly been dismantled between yesterday morning and today. Piece by piece throughout the day. What, the new administration will no longer support or tolerate discussion of research affecting the health of >50% of humans? Seriously?!?

Join researchers across the country in fighting restrictions on the NIH Please click the link to complete this form.

Academic workers across the country are organizing to call on our congressional representatives on Thursday, 1/30, at 3pm ET / 12pm PT to demand these restrictions be lifted immediately.
There will be a training over zoom at the beginning of the event.
Join us!
form.jotform.com/250226137228...

Modern GWAS can identify 1000s of significant hits but it can be hard to turn this into biological insight. What key cellular functions link genetic variation to disease?

I'm very excited to present our new work combining associations and Perturb-seq to build interpretable causal graphs! A 🧵

Very excited about this new work from our lab! Explainer thread coming soon
@minetoota.bsky.social

How population stratification makes environments look like genes. A short 🧵:

Cellular behavior analysis from live-cell imaging of TCR T cell–cancer cell interactions T cell therapies, such as chimeric antigen receptor (CAR) T cells and T cell receptor (TCR) T cells, are a growing class of anti-cancer treatments. However, expansion to novel indications and beyond l...

First post in the Good Place! Our preprint on cellular behavior analysis in TCR T cells & cancer cell live-cell imaging data is out! This 3-year collaboration led by pd Archit Verma w/ Alex Marson & Julia Carnevale, with segmentation & tracking by @davidvv & team! www.biorxiv.org/content/10.1...

A great paper and a great thread! One point that I partcularly liked was this one:
"In particular, [GWAS] variants can be trait specific in two ways: they can either affect a trait-specific gene or affect a pleiotropic gene in a context-specific manner."

Specificity, length, and luck: How genes are prioritized by rare and common variant association studies Standard genome-wide association studies (GWAS) and rare variant burden tests are essential tools for identifying trait-relevant genes. Although these methods are conceptually similar, we show by anal...

What do GWAS and rare variant burden tests discover, and why?

Do these studies find the most IMPORTANT genes? If not, how DO they rank genes?

Here we present a surprising result: these studies actually test for SPECIFICITY! A 🧵on what this means... (🧪🧬)

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

Why do association studies prioritize trait-specific variants???

A quick thread about the importance of thinking about all traits at once 👇 1/6 (🧪🧬)

Central control of dynamic gene circuits governs T cell rest and activation - Nature Resting and activated T cell states are established by context-specific regulators and dynamic gene circuits.

Beautiful work led by Maya Arce from Marson lab reveals a fascinating story about rewiring of a critical gene regulatory circuit in different T cell types: T effectors and Tregs
www.nature.com/articles/s41...

Leveraging functional annotations to map rare variants associated with Alzheimer's disease with gruyere The increasing availability of whole-genome sequencing (WGS) has begun to elucidate the contribution of rare variants (RVs), both coding and non-coding, to complex disease. Multiple RV association tes...

Excited to share our first foray into (noncoding) rare variant association testing: a probabilistic model that learns functional annotation importance and finds associations missed by existing methods. Anjali did a fantastic job with model assessment and scaling! www.medrxiv.org/content/10.1...

Our study is up! Context-specificity galore -- we explore genetic regulation of gene expression across many cell types and temporal states simultaneously in an efficient experimental system + scRNA-seq:

In vitro systems like this one offer an efficient way to explore gene regulation across many contexts that have been tricky to study thus far: like the cell types and transient cell states that arise during differentiation

To understand the molecular impacts of genetic variation, we need to look beyond healthy adult tissues, and even beyond healthy adult cell types

Cell type and dynamic state govern genetic regulation of gene expression in heterogeneous differentiating cultures Popp et al. generate dozens of cell types from 53 human iPSC lines in order to characterize the dynamic genetic regulation of gene expression across early stages of cellular differentiation. Accessing...

Excited to see our study on genetic regulation in heterogeneous differentiating cultures out in final form!

www.cell.com/cell-genomics/fulltext/S2666-979X(24)00330-6