I'm excited to share that our work studying gene dosage response curves (GDRCs) is now out in Cell Genomics (@cellpress.bsky.social). www.cell.com/cell-genomic... [1/n]

Buffering of gene dosage response curves for human complex traits

Milind et al. explore why loss-of-function variants and duplications tend to have average effects in the same direction on 94 complex traits. Using gene dosage response curves (GDRCs), they gather evi...

cell.com

Why do schizophrenia GWAS signals look so flat across the genome? In our recent preprint, we explored why psychiatric disorders — and, more broadly, brain-related traits involving the central nervous system — appear to have unusual genetic architectures. 🧵1/n

It's out! I hope this work encourages folks to move beyond a standard "one variant, one gene" QTL paradigm and consider proxitropic variant effects. Big thanks to the reviewers and editors at @ajhgnews.bsky.social for their help! @sbmontgom.bsky.social www.sciencedirect.com/science/arti...

Together with @ronghuizhu.bsky.social, we are thrilled to present our new perturb-seq study of 22M primary CD4+ T cells, across donors and timepoints – the result of a decade-long collaboration between the Marson @marsonlab.bsky.social and Pritchard @jkpritch.bsky.social labs 🧵 tinyurl.com/gwt2025

Genome-scale perturb-seq in primary human CD4+ T cells maps context-specific regulators of T cell programs and human immune traits

Gene regulatory networks encode the fundamental logic of cellular functions, but systematic network mapping remains challenging, especially in cell states relevant to human biology and disease. Here, ...

tinyurl.com

How well does TWAS estimate a gene’s direction of effect on a trait? We think of this as an important stress-test for the accuracy of TWAS. In a new pre-print, we find that TWAS gets the sign wrong around 20-30% of the time! doi.org/10.64898/202... 1/n

High false sign rates in transcriptome-wide association studies

Transcriptome-wide association studies (TWAS) are widely used to identify genes involved in complex traits and to infer the direction of gene effects on traits. However, despite their popularity, it r...

doi.org

Cancer Discovery #ResearchWatch: High-risk ER+ #BreastCancers Genomically Resemble HER2+ Tumors, a summary of the study by @khoulahan.bsky.social, @lisemangiante.bsky.social, @crissotomayor.bsky.social, @alvinahere.bsky.social, @cncurtis.bsky.social + colleagues @ Stanford doi.org/10.1158/2159...

High-risk ER+ Breast Cancers Genomically Resemble HER2+ Tumors

Main Finding: HER2+ breast tumors and high-risk ER+ breast tumors share genomic features that reflect similar mechanisms of tumor evolution.Concept: The genomic architecture of breast cancer is constr...

doi.org

I’m super excited to share what I’ve been working on for the last (many) years: a spatial + genomic + transcriptomic characterization of how the breast cancer microenvironment evolves through immunotherapy! (1/x) 🧪🧬 🖥️ #AcademicSky #MLSky #ImmunoSky www.biorxiv.org/content/10.1...

Temporal and spatial composition of the tumor microenvironment predicts response to immune checkpoint inhibition

Immune checkpoint inhibition (ICI) has fundamentally changed cancer treatment. However, only a minority of patients with metastatic triple negative breast cancer (TNBC) benefit from ICI, and the deter...

biorxiv.org

Thrilled to share the first paper of my PhD! It was so much fun working on this collaborative project from day one as a rotation student! Huge thanks @khoulahan.bsky.social, @lisemangiante.bsky.social, @crissotomayor.bsky.social, @cncurtis.bsky.social, Jennifer Caswell-Jin & the Curtis lab!

Katie Houlahan@khoulahan.bsky.social · 2y ago

The Curtis Lab’s latest study on the genomic architecture of breast cancer from the pre-invasive to metastatic setting is now out in Nature! www.nature.com/articles/s41...