Evidence map›Paper›PMID 42098110›Full record

ArticleNature communications2026

SCOTCH: isoform-level characterization of gene expression through long-read single-cell RNA sequencing.

Zhuoran Xu, Hui-Qi Qu, Joe Chan, Shizhuo Mu, Charlly Kao, Hakon Hakonarson, Kai Wang

Abstract read
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
  2. Review
  3. Risk of Alzheimer's disease in Down syndrome: Insights gained by multi-omics.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Review
  4. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors.

Zhuoran XuGraduate Group in Genomics and Computational Biology, University of Pennsylvania, Philadelphia, PA, USA.
Hui-Qi QuThe Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0001-9317-4488
Joe ChanRaymond G. Perelman Center for Cellular and Molecular Therapeutics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-5627-6693
Shizhuo MuRaymond G. Perelman Center for Cellular and Molecular Therapeutics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Charlly KaoThe Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Hakon HakonarsonThe Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0003-2814-7461
Kai WangRaymond G. Perelman Center for Cellular and Molecular Therapeutics, Children's Hospital of Philadelphia, Philadelphia, PA, USA. wangk@chop.edu.ORCID http://orcid.org/0000-0002-5585-982X

Funding

The Intellectual and Developmental Disabilities Research Center (IDDRC) at CHOP/PennP50HD105354 · NICHD · CHILDREN'S HOSP OF PHILADELPHIA · PI ERIC D MARSH, ROBERT Thomas SCHULTZ · 2021 to 2026
$9.2M
Novel bioinformatics methods to detect DNA and RNA modifications using Nanopore long-read sequencingR01HG013359 · NHGRI · CHILDREN'S HOSP OF PHILADELPHIA · PI Kai Wang · 2023 to 2026
$2.8M
Detection and annotation of structural variants from long-read sequencingR01GM132713 · NIGMS · CHILDREN'S HOSP OF PHILADELPHIA · PI WANG, KAI · 2019 to 2022
$1.9M
NHGRI NIH HHS R01 HG013359NICHD NIH HHS P50 HD105354NIGMS NIH HHS R01 GM132713U.S. Department of Health & Human Services | National Institutes of Health (NIH) GM132713U.S. Department of Health & Human Services | National Institutes of Health (NIH) HD105354U.S. Department of Health & Human Services | National Institutes of Health (NIH) HG013359
6 · The paper itself

Abstract

Recent advances in long-read single-cell transcriptome sequencing (lr-scRNA-Seq) enable full-length isoform profiling at single-cell resolution. We present SCOTCH (Single-Cell Omics for Transcriptome CHaracterization), an end-to-end, platform-independent pipeline for isoform characterization from lr-scRNA-Seq data, supporting Nanopore and PacBio sequencing as well as 10X Genomics and Parse Biosciences protocols. SCOTCH models isoforms as combinations of non-overlapping sub-exons and applies dynamic thresholding for robust isoform assignment while efficiently address ambiguous mapping issues. By refining sub-exon boundaries through integration of read coverage with existing annotations and applying an iterative clustering strategy to reconstruct novel transcripts, SCOTCH reliably recovers more true novel isoforms than existing splice-graph-based methods, with poly(A)-aware filtering further reducing false-positive structures. Extensive simulations demonstrate improved quantification of known isoforms and enhanced reconstruction of novel isoforms. Analyses of human blood and cerebral organoid datasets across multiple platforms further confirm SCOTCH's ability to resolve cell-type-specific transcriptome profiles and uncover experimentally supported novel isoforms.

Indexed as

Gene Expression ProfilingSequence Analysis, RNASingle-Cell AnalysisTranscriptomeAnimalsExonsHumansProtein IsoformsSingle-Cell Gene Expression AnalysisProtein Isoforms

Identifiers

PMID42098110
PMCPMC13365210

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.