ArticleNature communications2025
Long-read RNA-seq demarcates cis- and trans-directed alternative RNA splicing.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- The promise of long-read RNA-seq: reducing bias in analyses of allele imbalance.NAR genomics and bioinformatics · 2026Article
- The Encyclopedia of DNA Elements.bioRxiv : the preprint server for biology · 2026Article
- Transcriptome Reprogramming in Heart Failure: The Hidden Splicing Code.Current cardiology reports · 2026Review
- SNP calling, haplotype phasing and allele-specific analysis with long RNA-seq reads.Nature methods · 2026Article
- Sample-specific haplotype-resolved protein isoform characterization via long-read RNA-seq-based proteogenomics.bioRxiv : the preprint server for biology · 2026Article
- Long-Read Sequencing Reveals RNA Splicing Complexity in Human Diseases.Computational and structural biotechnology journal · 2026Review
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Authors and funding
3 authors.
Funding
Abstract
Genetic regulation of alternative splicing constitutes an important link between genetic variation and disease. Nonetheless, RNA splicing is regulated by both cis-acting elements and trans-acting splicing factors. Determining splicing events that are directed primarily by the cis- or trans-acting mechanisms will greatly inform our understanding of the genetic basis of disease. Here, we show that long-read RNA-seq, combined with our new method isoLASER, enables a clear segregation of cis- and trans-directed splicing events for individual samples. The genetic linkage of splicing is largely individual-specific, in stark contrast to the tissue-specific pattern of splicing profiles. Analysis of long-read RNA-seq data from human and mouse revealed thousands of cis-directed splicing events susceptible to genetic regulation. We highlight such events in the HLA genes whose analysis was challenging with short-read data. We also highlight novel cis-directed splicing events in Alzheimer's disease-relevant genes such as MAPT and BIN1. Together, the clear demarcation of cis- and trans-directed splicing paves ways for future studies of the genetic basis of disease.
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Registered trials
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