Postdoc @ Genentech | PhD from Stanford Biomedical Data Science.
Matthew Aguirre
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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...
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Two, looking forward, we’re seeing real traction in causal modeling of cell states and processes (see recent perturbation screens + GRN inference + “virtual cell” literature) and alignment with human genetics (another type of causal “anchor”)
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www.cell.com
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...
This type of data integration has some very exciting future directions — and in my opinion, it benefits greatly from understanding the nature of the relevant problems. Let us know what you think of our work!
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Complete betrayal of the country. Total Congressional abdication.
Matthew Aguirre
Due to these features, trans-eQTL effects are: (1) mostly 1-2 hops away from a given gene; (2) less polygenic than expected, “up” the GRN from that gene; (3) quite pleiotropic, “down” the GRN from a regulator.
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The intuition hinges on the fact that GRNs have characteristic features (sparsity, modularity, hub regulators, motifs, etc.). Surprisingly, even basic eQTL summary statistics imply that GRNs are organized this way.
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Why am I excited about this? One, it suggests a direction and gives reason for optimism in trans-xQTL studies, assuming cell phenotypes are low-dimensional compared to what we measure (cf. our prior work on gene perturbations).
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It’s been known that genetic effects on traits are not always where we might expect. Our main contribution here is mathematically grounded intuition for how distal trans-regulatory effects should be distributed on realistic causal networks, and what those networks look like.
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We built a joint experimental and computational platform for scalable multi-modal single-cell chemical screens — profiling RNA, protein (including phospho-signaling), and chromatin accessibility responses to thousands of small molecule perturbations in parallel. www.biorxiv.org/content/10.6...
Happy to share that this is now out in Cell Genomics and a featured paper for Multi-Journal Submission from @cellpress.bsky.social — many thanks to the editorial team + our reviewers!
Short recap + some further thoughts on the paper ⬇️ [1/7]
www.cell.com/cell-genomic...
