Evidence map›Paper›PMID 39567236›Full record

ReviewGenome research2024

Challenges in identifying mRNA transcript starts and ends from long-read sequencing data.

Ezequiel Calvo-Roitberg, Rachel F Daniels, Athma A Pai

Abstract readReview
In one paragraph

Review in Genome research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing 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

25 citing papers in PubMed.

  1. Review
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  8. bioRxiv : the preprint server for biology · 2025
    Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Review
  14. Perplexity as a Metric for Isoform Diversity in the Human Transcriptome.bioRxiv : the preprint server for biology · 2025
    Article
  15. Review
  16. Article
  17. Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

3 authors.

Ezequiel Calvo-RoitbergRNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, Massachusetts 01605, USA.ORCID 0000-0002-2431-515X
Rachel F DanielsRNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, Massachusetts 01605, USA.ORCID 0000-0002-9712-4581
Athma A PaiRNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, Massachusetts 01605, USA athma.pai@umassmed.edu.ORCID 0000-0002-7995-9948

Funding

Tracking transcriptome diversity in real-timeR35GM133762 · NIGMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI Athma A Pai · 2019 to 2026
$3.3M
A kinetic framework to map the genetic determinants of alternative RNA isoform expressionR01HG012967 · NHGRI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI Barbara Engelhardt, Athma A Pai · 2023 to 2026
$3.0M
Development of essential research tools for sustaining global programs for the elimination of human hookwormsR21AI166281 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI CAMPBELL, ELYSSA, DANIELS, RACHEL FATH · 2022 to 2023
$453k
NHGRI NIH HHS R01 HG012967NIAID NIH HHS R21 AI166281NIGMS NIH HHS R35 GM133762
6 · The paper itself

Abstract

Long-read sequencing (LRS) technologies have the potential to revolutionize scientific discoveries in RNA biology through the comprehensive identification and quantification of full-length mRNA isoforms. Despite great promise, challenges remain in the widespread implementation of LRS technologies for RNA-based applications, including concerns about low coverage, high sequencing error, and robust computational pipelines. Although much focus has been placed on defining mRNA exon composition and structure with LRS data, less careful characterization has been done of the ability to assess the terminal ends of isoforms, specifically, transcription start and end sites. Such characterization is crucial for completely delineating full mRNA molecules and regulatory consequences. However, there are substantial inconsistencies in both start and end coordinates of LRS reads spanning a gene, such that LRS reads often fail to accurately recapitulate annotated or empirically derived terminal ends of mRNA molecules. Here, we describe the specific challenges of identifying and quantifying mRNA terminal ends with LRS technologies and how these issues influence biological interpretations of LRS data. We then review recent experimental and computational advances designed to alleviate these problems, with ideal use cases for each approach. Finally, we outline anticipated developments and necessary improvements for the characterization of terminal ends from LRS data.

Indexed as

RNA, MessengerSequence Analysis, RNAComputational BiologyExonsHigh-Throughput Nucleotide SequencingHumansTranscription Initiation SiteRNA, Messenger

Identifiers

PMID39567236
PMCPMC11610588

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

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.