Evidence map›Paper›PMID 34649612›Full record

ArticleGenome biology2021

Benchmarking sequencing methods and tools that facilitate the study of alternative polyadenylation.

Ankeeta Shah, Briana E Mittleman, Yoav Gilad, Yang I Li

Open access · goldAbstract readEvaluation Study
In one paragraph

Article in Genome biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
2.4field-weighted citation impact, top 10% of its field
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

28 citing papers in PubMed, 37 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

Ankeeta ShahGenetics, Genomics, and Systems Biology, University of Chicago, Chicago, IL, USA.ORCID 0000-0001-8291-4401
Briana E MittlemanGenetics, Genomics, and Systems Biology, University of Chicago, Chicago, IL, USA.
Yoav GiladSection of Genetic Medicine, Department of Medicine, University of Chicago, Chicago, IL, USA.
Yang I LiSection of Genetic Medicine, Department of Medicine, University of Chicago, Chicago, IL, USA. yangili1@uchicago.edu.
University of Chicago · US

Funding

PREDOCTORAL TRAINING IN GENETICS AND REGULATIONT32GM007197 · NIGMS · UNIVERSITY OF CHICAGO · PI ROTHMAN-DENES, LUCIA B. B · 1985 to 2020
$17.0M
Characterizing and Understanding Variation in Gene Regulatory Mechanisms Within and Between Species'R35GM131726 · NIGMS · UNIVERSITY OF CHICAGO · PI Yoav Gilad · 2019 to 2026
$3.7M
Investigating the co-transcriptional impact of genetic variation on gene regulation and diseaseR01GM130738 · NIGMS · UNIVERSITY OF CHICAGO · PI LI, YANG · 2019 to 2023
$2.2M
NIGMS NIH HHS R01 GM130738NIGMS NIH HHS R35 GM131726NIGMS NIH HHS T32 GM007197
6 · The paper itself

Abstract

backgroundAlternative cleavage and polyadenylation (APA), an RNA processing event, occurs in over 70% of human protein-coding genes. APA results in mRNA transcripts with distinct 3' ends. Most APA occurs within 3' UTRs, which harbor regulatory elements that can impact mRNA stability, translation, and localization.

resultsAPA can be profiled using a number of established computational tools that infer polyadenylation sites from standard, short-read RNA-seq datasets. Here, we benchmarked a number of such tools-TAPAS, QAPA, DaPars2, GETUTR, and APATrap- against 3'-Seq, a specialized RNA-seq protocol that enriches for reads at the 3' ends of genes, and Iso-Seq, a Pacific Biosciences (PacBio) single-molecule full-length RNA-seq method in their ability to identify polyadenylation sites and quantify polyadenylation site usage. We demonstrate that 3'-Seq and Iso-Seq are able to identify and quantify the usage of polyadenylation sites more reliably than computational tools that take short-read RNA-seq as input. However, we find that running one such tool, QAPA, with a set of polyadenylation site annotations derived from small quantities of 3'-Seq or Iso-Seq can reliably quantify variation in APA across conditions, such asacross genotypes, as demonstrated by the successful mapping of alternative polyadenylation quantitative trait loci (apaQTL).

conclusionsWe envisage that our analyses will shed light on the advantages of studying APA with more specialized sequencing protocols, such as 3'-Seq or Iso-Seq, and the limitations of studying APA with short-read RNA-seq. We provide a computational pipeline to aid in the identification of polyadenylation sites and quantification of polyadenylation site usages using Iso-Seq data as input.

Indexed as

PolyadenylationRNA-SeqSoftwareBenchmarkingCell LineGenome, HumanHumans3′-SeqAlternative polyadenylationBenchmarkingIsoform analysisLong-read sequencingPacBio Iso-SeqQTLRNA processingRNA-seq

Identifiers

PMID34649612
PMCPMC8518154
OpenAlexW3205892321

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.