iiinova — where your digital self keeps evolving

Wei-Lin Qiu

@613weilin.bsky.social

Postdoctoral Researcher in Robin Andersson lab at University of Copenhagen

Wei-Lin Qiu @613weilin.bsky.social · 25/11/2024

Many thanks to our amazing team, especially co-first author @mayayayas.bsky.social, and supervisors @randersson.bsky.social, @jengreitz.bsky.social 12/12

000

Wei-Lin Qiu @613weilin.bsky.social · 25/11/2024

You can run scE2G on your data today using our pipeline here: github.com/EngreitzLab/... We are looking forward to hearing your feedback on how scE2G works on your dataset! 11/12

github.com

GitHub - EngreitzLab/scE2G at v1.0

Pipeline to run scE2G. Contribute to EngreitzLab/scE2G development by creating an account on GitHub.

112

Wei-Lin Qiu @613weilin.bsky.social · 25/11/2024

We have also applied scE2G to identify and validate disease-related enhancers in the human coronary artery and fetal heart – check out these preprints to learn more! Coronary artery: www.medrxiv.org/content/10.1... Fetal heart: www.medrxiv.org/content/10.1... 10/12

medrxiv.org

Single cell variant to enhancer to gene map for coronary artery disease

Although genome wide association studies (GWAS) in large populations have identified hundreds of variants associated with common diseases such as coronary artery disease (CAD), most disease-associated...

120

Wei-Lin Qiu @613weilin.bsky.social · 25/11/2024

We also integrate scE2G predictions with orthogonal information to prioritize causal genes and cell types for noncoding variants associated with complex traits. For example, here we nominate regulatory interactions linking INPP4B and IL15 to lymphocyte counts in T cells. 9/12

100

Wei-Lin Qiu @613weilin.bsky.social · 25/11/2024

For example, here we identify cell-type specific links for SPTA1 in erythroblasts and normoblasts. 8/12

100

Wei-Lin Qiu @613weilin.bsky.social · 25/11/2024

We applied scE2G to over 40 cell types from PBMCs, BMMCs, and pancreatic islets, validating that scE2G predictions reflect expected patterns of cell-type specificity. 7/12

100

Wei-Lin Qiu @613weilin.bsky.social · 25/11/2024

We show that scE2G has robust performance for cell types with at least 2 million total ATAC fragments and 1 million RNA UMIs – about 200-400 cells from a typical 10x Multiome experiment in a tissue. 6/12

100

Wei-Lin Qiu @613weilin.bsky.social · 25/11/2024

Key features in scE2G include 1) ABC score, 2) Kendall correlation between peak accessibility and gene expression, and 3) whether the gene is “ubiquitously-expressed”. Notably, the Kendall correlation improves long-range predictions and appears to detect stochastic transcriptional bursting. 5/12

110

Wei-Lin Qiu @613weilin.bsky.social · 25/11/2024

In systematic benchmarking against CRISPR perturbations (below), fine-mapped eQTLs, and GWAS variant-gene associations, scE2G models outperforms existing single-cell models and distance-derived baselines. We applied and extended ENCODE benchmarking pipelines: www.biorxiv.org/content/10.1... 4/12

101

Wei-Lin Qiu @613weilin.bsky.social · 25/11/2024

Using a gold-standard CRISPR perturbation dataset, we trained two logistic regression models: scE2G (ATAC) and scE2G (Multiome), that use single-cell ATAC-seq or single-cell multiomic ATAC and RNA-seq data, respectively. 3/12

110

Wei-Lin Qiu @613weilin.bsky.social · 25/11/2024

scE2G tackles the challenge of building cell-type-specific maps of enhancer-gene regulation. If we can do this well, we can build enhancer maps across thousands of human cell types from emerging single-cell atlases to interpret genetic variants and understand gene regulation. 2/12

100

Wei-Lin Qiu @613weilin.bsky.social · 25/11/2024

Excited to share our latest preprint on scE2G – a new model to link enhancers to target genes using single-cell data – with state-of-the-art performance across multiple perturbation benchmarks. biorxiv.org/cgi/content/... Read more below! 1/12

biorxiv.org

Mapping enhancer-gene regulatory interactions from single-cell data

Mapping enhancers and their target genes in specific cell types is crucial for understanding gene regulation and human disease genetics. However, accurately predicting enhancer-gene regulatory interac...

14320