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Cited by 107RNA Research and SplicingRNA regulation and diseaseCancer-related molecular mechanisms research

ASCOT identifies key regulators of neuronal subtype-specific splicing

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Ling, Jonathan P., Wilks, Christopher, Charles, Rone, Leavey, Patrick J., Ghosh, Devlina, Jiang, Lizhi, Santiago, Clayton P., Pang, Bo +5 more·2020·Nature Communications
DOI 10.1038/s41467-019-14020-5PMC PMC6952364

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Abstract

Public archives of next-generation sequencing data are growing exponentially, but the difficulty of marshaling this data has led to its underutilization by scientists. Here, we present ASCOT, a resource that uses annotation-free methods to rapidly analyze and visualize splice variants across tens of thousands of bulk and single-cell data sets in the public archive. To demonstrate the utility of ASCOT, we identify novel cell type-specific alternative exons across the nervous system and leverage ENCODE and GTEx data sets to study the unique splicing of photoreceptors. We find that PTBP1 knockdown and MSI1 and PCBP2 overexpression are sufficient to activate many photoreceptor-specific exons in HepG2 liver cancer cells. This work demonstrates how large-scale analysis of public RNA-Seq data sets can yield key insights into cell type-specific control of RNA splicing and underscores the importance of considering both annotated and unannotated splicing events.

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  • Predicted versus observed splice junction read counts (log(1 + x) transformed; n = 1,344,738) and Pearson r between them were assessed in selected human tissues known for having distinct splicing patterns.

    “Predicted versus observed splice junction read counts (log(1 + x) transformed; n = 1,344,738) and Pearson r between them in selected human tissues known for having distinct splicing patterns49.”

    From Advancing regulatory variant effect prediction with AlphaGenome (2026) · cites this paper as [49]

    The Methods section on Snaptron compilations describes tables of observed splice-junction counts, and the Results discuss splicing patterns in human tissues. Neither passage reports a predicted-versus-observed count comparison, a log(1 + x) transformation, Pearson r, or n = 1,344,738. Searches for those terms found no matching passage in our copy. (LLM, conf=0.72)

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References 77 · Cited by 107

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Authors
Ling, J. P., Wilks, C., Charles, R., Leavey, P. J., Ghosh, D., Jiang, L., Santiago, C. P., Pang, B., Venkataraman, A., Clark, B. S., Nellore, A., Langmead, B., & Blackshaw, S.
Affiliations
  • Johns Hopkins University (US)
  • Washington University in St. Louis (US)
  • Oregon Health & Science University (US)
Corresponding author
  • Langmead, Ben
  • Blackshaw, Seth
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2020-01-09
Volume
11
Issue
1
Pages
137-137
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-019-14020-5
PMC
PMC6952364
OpenAlex
W3000436287
Cited by
107
References
77
Citations by year
2026: 6 · 2025: 16 · 2024: 45 · 2023: 11 · 2022: 11 · 2021: 16 · 2020: 2
FWCI
3.24
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Digital Commons@Becker (Washington University School of Medicine) (submittedVersion, cc-by)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (R01GM118568, R01GM121459)
  • U.S. Department of Health & Human Services | NIH | National Eye Institute (R01EY020560)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
Keywords
ASCOT, alternative splicing, cell-type-specific splicing, neuronal cell types, photoreceptors, alternative exons, PTBP1, MSI1, PCBP2, splice variants, single-cell RNA sequencing, HepG2 cells
MeSH terms
Data Analysis, Animals, Humans, Liver Neoplasms, Nerve Tissue Proteins, Neurons, Photoreceptor Cells, Retina, Gene Expression, RNA-Binding Proteins, Alternative Splicing, Sequence Analysis, RNA, Computational Biology, RNA Splice Sites, Heterogeneous-Nuclear Ribonucleoproteins, Polypyrimidine Tract-Binding Protein, Cell Line, Tumor, Mice, Hep G2 Cells, High-Throughput Nucleotide Sequencing

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