iiinova — where your digital self keeps evolving

Kaili Fan @kailifan.bsky.social · 05/10/2026

12/13 Cellular context matters: the same gene or variant can behave differently in different cells. This atlas helps prioritize which regulatory element may influence which gene—and in which cell.

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Kaili Fan @kailifan.bsky.social · 05/10/2026

11/13 Even within a shared lineage, context mattered. Models of 8 endothelial subtypes resolved distinct predicted effects across vascular beds, including subtype-specific effects near SMAD6.

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Kaili Fan @kailifan.bsky.social · 05/10/2026

10/13 We next modeled the effects of 548,656 fine-mapped trait- and disease-associated variants across 35 primary cell types. We identified 18,133 variants with large predicted accessibility effects. Most were cell-type restricted; 1,120 had broadly distributed effects.

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Kaili Fan @kailifan.bsky.social · 05/10/2026

9/13 These “locked” regions overlapped independently measured heterochromatin by 79.3%. They were also preferentially hypomethylated in tumors across many cancer types, with different domains affected in different cancers.

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Kaili Fan @kailifan.bsky.social · 05/10/2026

8/13 We then zoomed out from individual regulatory elements. Across 26,502 genomic windows, we identified broadly accessible, lineage-selective, and constitutively inaccessible domains. 10.2% of the analyzed genome was constitutively inaccessible.

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Kaili Fan @kailifan.bsky.social · 05/10/2026

7/13 The same gene can use different regulatory circuits in different cells. For example, FOS was associated with substantially different regulatory elements in T cells and smooth muscle cells.

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Kaili Fan @kailifan.bsky.social · 05/10/2026

6/13 We mapped 871,177 cell-type-specific regulatory element–gene associations. Genomic proximity was not always enough: 36% of distal associations involved a non-nearest gene.

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Kaili Fan @kailifan.bsky.social · 05/10/2026

5/13 Regulatory activity reflected both cell identity and tissue context. Shared cell types preserved a core regulatory program across organs, while a smaller set of elements adapted to the local tissue environment.

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Kaili Fan @kailifan.bsky.social · 05/10/2026

4/13 We mapped 1,085,062 candidate regulatory elements across the genome, including 161,270 absent from the ENCODE registry. Novel elements were enriched for transposable-element sequence, showed lower evolutionary conservation, and were more cell-type-specific.

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Kaili Fan @kailifan.bsky.social · 05/10/2026

3/13 Integrating RNA and chromatin accessibility resolved: • 9 cell lineages • 61 broad cell types • 313 finer transcriptional subclusters This provided a common framework for comparing regulatory programs across the body.

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Kaili Fan @kailifan.bsky.social · 05/10/2026

2/13 We profiled 459,856 nuclei from 21 tissues and 4 adult donors, including 160,688 nuclei with paired RNA and chromatin-accessibility. That pairing lets us relate accessible regulatory DNA to gene expression in the same nuclei.

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Kaili Fan @kailifan.bsky.social · 05/10/2026

1/13 The human body runs on one genome—but every cell reads it differently. How? To find out, we need to measure both gene expression and chromatin accessibility in the same nucleus. So we did, across 21 adult tissues and nearly half a million nuclei. 🧵 🔗 www.biorxiv.org/content/10.6...

biorxiv.org

Single-Nucleus Multi-Omic Atlas Maps Regulatory Architecture and Non-Coding Variant Effects across Adult Human Tissues

Diverse human cell types establish specialized functions through lineage- and context-specific regulatory programs. Interpreting non-coding genetic risk requires integrated multi-omic reference maps t...

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Reposted by Kaili Fan

UMass Chan Medical School @umasschan.bsky.social · 17/03/2025

Working with a team at the University of Queensland, UMass Chan scientists have discovered that a population of koalas has evolved genomic immunity to a retrovirus: direc.to/mDfy #koalas @lubanlab.bsky.social @tianxiong-bear-yu.bsky.social

William E. Theurkauf, PhD; Jeremy Luban, MD; Tianxiong Yu, PhD; and Zhiping Weng, PhD

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Kaili Fan @kailifan.bsky.social · 09/03/2025

🌟 Check out this fascinating study exploring how genomes combat real-time virus invasions—a UNIQUE approach to studying evolution as it happens! Huge congratulations to @tianxiong-bear-yu.bsky.social and the entire team for yet another set of remarkable findings! 🎉🎉

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Kaili Fan @kailifan.bsky.social · 16/01/2025

Thrilled to join this incredible project! Stay tuned for exciting discoveries ahead!

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Reposted by Kaili Fan

Tim Coorens @timcoorens.bsky.social · 15/01/2025

Our new perspective article describing the human and non-human primate developmental GTEx projects is now out in @nature.com! We outline the scope, vision, opportunities and challenges of these projects here: www.nature.com/articles/s41...

nature.com

The human and non-human primate developmental GTEx projects - Nature

The developmental Genotype-Tissue Expression (dGTEx) projects will catalogue and integrate gene expression, regulation and genetics data across 120 human donors from birth to adulthood with developmen...

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