Evidence map›Paper›PMID 38925112›Full record

ArticleCell2024

Multiplexed single-cell characterization of alternative polyadenylation regulators.

Madeline H Kowalski, Hans-Hermann Wessels, Johannes Linder, Carol Dalgarno, Isabella Mascio, Saket Choudhary, Austin Hartman, Yuhan Hao, Anshul Kundaje, Rahul Satija

Abstract read
In one paragraph

Article in Cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing 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

37 citing papers in PubMed.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Madeline H KowalskiNew York Genome Center, New York, NY, USA; Center for Genomics and Systems Biology, New York University, New York, NY, USA; New York University Grossman School of Medicine, New York, NY, USA.
Hans-Hermann WesselsNew York Genome Center, New York, NY, USA; Center for Genomics and Systems Biology, New York University, New York, NY, USA. Electronic address: wesselshanshermann@gmail.com.
Johannes LinderDepartment of Genetics, Stanford University, Stanford, CA, USA; Department of Computer Science, Stanford University, Stanford, CA, USA.
Carol DalgarnoNew York Genome Center, New York, NY, USA.
Isabella MascioNew York Genome Center, New York, NY, USA; Center for Genomics and Systems Biology, New York University, New York, NY, USA.
Saket ChoudharyNew York Genome Center, New York, NY, USA; Center for Genomics and Systems Biology, New York University, New York, NY, USA.
Austin HartmanNew York Genome Center, New York, NY, USA.
Yuhan HaoNew York Genome Center, New York, NY, USA; Center for Genomics and Systems Biology, New York University, New York, NY, USA.
Anshul KundajeDepartment of Genetics, Stanford University, Stanford, CA, USA; Department of Computer Science, Stanford University, Stanford, CA, USA.
Rahul SatijaNew York Genome Center, New York, NY, USA; Center for Genomics and Systems Biology, New York University, New York, NY, USA; New York University Grossman School of Medicine, New York, NY, USA. Electronic address: rsatija@nygenome.org.

Funding

Center for Integrated Cellular Analysis - Valeria A. Sanchez EstradaRM1HG011014 · NHGRI · NEW YORK GENOME CENTER · PI LANDAU, DAN, SATIJA, RAHUL · 2020 to 2025
$22.1M
GENCODE: comprehensive reference genome annotation for human and mouseU24HG007234 · NHGRI · EUROPEAN MOLECULAR BIOLOGY LABORATORY · PI Fergal James Martin · 2021 to 2026
$16.1M
Comprehensive reference atlas construction, geolocation and data integration for HuBMAP HIVE [5 of 5]OT2OD033760 · OD · NEW YORK GENOME CENTER · PI SATIJA, RAHUL · 2022 to 2025
$6.1M
Decoding the Molecular Basis of Dysregulated Cleavage and Polyadenylation in Myeloid Malignancies - Resubmission - 1F30CA287962 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI Madeline Heidi Kowalski · 2024 to 2026
$127k
NCI NIH HHS F30 CA287962NHGRI NIH HHS RM1 HG011014NHGRI NIH HHS U24 HG007234NIH HHS OT2 OD033760
6 · The paper itself

Abstract

Most mammalian genes have multiple polyA sites, representing a substantial source of transcript diversity regulated by the cleavage and polyadenylation (CPA) machinery. To better understand how these proteins govern polyA site choice, we introduce CPA-Perturb-seq, a multiplexed perturbation screen dataset of 42 CPA regulators with a 3' scRNA-seq readout that enables transcriptome-wide inference of polyA site usage. We develop a framework to detect perturbation-dependent changes in polyadenylation and characterize modules of co-regulated polyA sites. We find groups of intronic polyA sites regulated by distinct components of the nuclear RNA life cycle, including elongation, splicing, termination, and surveillance. We train and validate a deep neural network (APARENT-Perturb) for tandem polyA site usage, delineating a cis-regulatory code that predicts perturbation response and reveals interactions between regulatory complexes. Our work highlights the potential for multiplexed single-cell perturbation screens to further our understanding of post-transcriptional regulation.

Indexed as

Poly APolyadenylationSingle-Cell AnalysisAnimalsGene Expression RegulationHumansIntronsMiceRNA, MessengerTranscriptomePoly ARNA, Messengeralternative polyadenylationcleavage and polyadenylationPerturb-seqpost-transcriptional regulationRNA processing

Identifiers

PMID38925112
PMCPMC12052259

What OpenQuestion holds

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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.