Evidence map›Paper›PMID 37043539›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2023

A genome-wide optical pooled screen reveals regulators of cellular antiviral responses.

Rebecca J Carlson, Michael D Leiken, Alina Guna, Nir Hacohen, Paul C Blainey

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
5.8field-weighted citation impact, top 4% 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

29 citing papers in PubMed, 36 citations in OpenAlex.

  1. Article
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  5. The one-week automated genome-wide optical pooled screen.bioRxiv : the preprint server for biology · 2026
    Article
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  7. Reimagining the Synthetic Biology DBTL Cycle with Machine Learning.Methods in molecular biology (Clifton, N.J.) · 2026
    Article
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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

5 authors at 2 institutions in 1 country.

Rebecca J CarlsonDepartment of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139.ORCID 0000-0002-5423-9717
Michael D LeikenBroad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142.
Alina GunaWhitehead Institute, Cambridge, MA 02142.ORCID 0000-0003-0757-1255
Nir HacohenBroad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142.ORCID 0000-0002-2349-2656
Paul C BlaineyBroad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142.ORCID 0000-0002-4889-8783
Broad Institute · USWhitehead Institute for Biomedical Research · US

Funding

Center for Cell CircuitsP50HG006193 · NHGRI · BROAD INSTITUTE, INC. · PI REGEV, AVIV · 2011 to 2015
$15.6M
Center for Cell CircuitsRM1HG006193 · NHGRI · BROAD INSTITUTE, INC. · PI BLAINEY, PAUL CLARK, HACOHEN, NIR · 2016 to 2020
$14.9M
High-content optical pooled genome-wide screens of SARS-CoV-2 infectionR01HG009283 · NHGRI · BROAD INSTITUTE, INC. · PI BLAINEY, PAUL CLARK · 2017 to 2020
$4.8M
Factors regulating strength and duration of STING signalingR01AI158495 · NIAID · BROAD INSTITUTE, INC. · PI HACOHEN, NIR · 2021 to 2025
$2.1M
NHGRI NIH HHS P50 HG006193NHGRI NIH HHS R01 HG009283NHGRI NIH HHS RM1 HG006193NIAID NIH HHS R01 AI158495
6 · The paper itself

Abstract

The infection of mammalian cells by viruses and innate immune responses to infection are spatiotemporally organized processes. Cytosolic RNA sensors trigger nuclear translocation of the transcription factor interferon regulatory factor 3 (IRF3) and consequent induction of host immune responses to RNA viruses. Previous genetic screens for factors involved in viral sensing did not resolve changes in the subcellular localization of host or viral proteins. Here, we increased the throughput of our optical pooled screening technology by over fourfold. This allowed us to carry out a genome-wide CRISPR knockout screen using high-resolution multiparameter imaging of cellular responses to Sendai virus infection coupled with in situ cDNA sequencing by synthesis (SBS) to identify 80,408 single guide RNAs (sgRNAs) in 10,366,390 cells-over an order of magnitude more genomic perturbations than demonstrated previously using an in situ SBS readout. By ranking perturbations using human-designed and deep learning image feature scores, we identified regulators of IRF3 translocation, Sendai virus localization, and peroxisomal biogenesis. Among the hits, we found that ATP13A1, an ER-localized P5A-type ATPase, is essential for viral sensing and is required for targeting of mitochondrial antiviral signaling protein (MAVS) to mitochondrial membranes where MAVS must be localized for effective signaling through retinoic acid-inducible gene I (RIG-I). The ability to carry out genome-wide pooled screens with complex high-resolution image-based phenotyping dramatically expands the scope of functional genomics approaches.

Indexed as

RNA VirusesSignal TransductionAnimalsAntiviral AgentsHumansImmunity, InnateInterferon Regulatory Factor-3MammalsRNAAntiviral AgentsInterferon Regulatory Factor-3RNACRISPR screeninghigh-content imagingIRF3RIG-ISendai

Identifiers

PMID37043539
PMCPMC10120039
OpenAlexW4365135118

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.