HUGE shoutout to our amazing team: Wang Wenjing, Liew Wei Lin, Liu Mei Hui, Xueling Sim, and Tai E Shyong!
19.07.2025 05:43
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HUGE shoutout to our amazing team: Wang Wenjing, Liew Wei Lin, Liu Mei Hui, Xueling Sim, and Tai E Shyong!
Colocalization with 12 Asian GWAS traits pinpoints 16 metabolic risk genes, revealing how lifestyle modulates genetic risk at loci like DHRS4L2 and YBX3.
Splicing QTLs (sQTLs) also respond to intervention, with attenuated regulation at T2D risk gene ANK1 and dynamic changes in mitochondrial genes.
We identify hundreds of lifestyle-responsive eQTLs, including context-specific regulation of ACTN3, NEB, and ATP2A1.
Muscle transcriptome rewiring reveals activation of insulin signaling and mitochondrial genes—plus significant shifts in alternative splicing.
We conducted a 16-week lifestyle intervention, which led to ~10% weight loss and improved insulin sensitivity, reshaping body composition and lipid metabolism.
Excited to share our new paper on Cell Genomics: We mapped how genetics shape the muscle transcriptome in response to exercise and diet intervention.
📄 www.cell.com/cell-genomic...
This is the third collaborative paper between the two labs. Looking forward to many projects to come!
Collaborative work led by Zhihao and me finally online at Nature Communications! nature.com/articles/s41...
Huge congratulations to Zhihao and his outstanding leadership. Also, to first author Foozhan Tahmasebinia, and key contributions from Yinglu Tang and Rushi Tang!
And here is the Nature Genetics Cover!
Exciting new benchmark for DNA language models!
This study is truly amazing.
The next Human Cell Atlas will be held in Singapore in June 2025. The early-bird registration is already open: 2025events.humancellatlas.org/2025GM
I highly encourage single-cell folks to register. Many exciting talks ahead!
In summary, we established a robust single-cell splicing analysis pipeline and uncovered functional regulatory pathways and novel disease mechanisms.
We also identified and validated a putative causal mechanism.
A genetic variant influencing the TCHP exon 4 inclusion, which putatively affects Graves' disease risk. We validated the variant-to-splicing relationship using a minigene assay.
We identified a pathway from genetic variants -> cis-eQTL (of a splicing factor) -> trans-sQTL (of a key T-cell differentiation marker) -> T-cell proportions (of naive vs. memory T cells). All of these are inferred using a single population-scale single-cell dataset.
Dynamic AS and dynamic sQTLs are widespread along the B-cell development trajectory, some of which may be implicated in disease. For example, PAX5 dynamic isoforms are key determinants of B cell differentiation, and CLEC2D dynamic sQTL is colocalized with autoimmune disease.
We observed significant improvement in exon coverage compared to 3' short-read data (4-6 fold!).
We established a robust pipeline to analyze alternative splicing using 10x 5' single-cell data. Because of "exon painting" effect, ~90% of exons are covered by 5' short-read, despite 5' bias. ~86% of short-read ss are replicated by long-read, likely more with more long-read samples.
Our paper on single-cell splicing QTL is now published as a cover article in Nature Genetics. www.nature.com/articles/s41...
Congratulations to co-first authors Chi Tian, Yihan Tong, and Yuntian Zhang! Huge thanks to AIDA leaders Shyam Prabhakar, @jayshin.bsky.social, Woong-Yang, and Kian Hong!
Very exciting work for biology and drug discovery!
QC is arguably the most important step in any single cell analysis. Low quality data can lead to incorrect conclusions.
HCA Asia 2024 off to a great start!
En route to HCA Hong Kong. Excited to reconnect with old friends and making new ones!
Comprehensive knockdown of 305 splicing-related proteins and their effect on splicing. Such a tour de force!!
Here is a starter pack for functional genomics on bluesky. Not sure if there is one already but do let me know if so. Let me know if you want to be added to the list.
go.bsky.app/SvBtD4d
Dear Su-In, I’m an assistant professor at the National University of Singapore. I would love to be included on your list. Thank you!!
The SG Academies South-East Asia Fellowship Programme (2024 Round) application is now open and will close on 31 Jan 2025. snas.org.sg/saseaf.
Is there a starter pack for functional genomics? Should I start one?
Has anyone used Video Byte or Graphical Abstract service by Springer Nature? Is it worth it?