Evidence map›Paper›PMID 37529368›Full record

ArticleCell reports methods2023

Integrative analysis of functional genomic screening and clinical data identifies a protective role for spironolactone in severe COVID-19.

Henry C Cousins, Adrienne Sarah Kline, Chengkun Wang, Yuanhao Qu, James Zengel, Jan Carette, Mengdi Wang, Russ B Altman, Yuan Luo, Le Cong

Open access · goldAbstract read
In one paragraph

Article in Cell reports methods, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.4field-weighted citation impact, top 46% 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

1 citing paper in PubMed, 4 citations in OpenAlex.

  1. Review
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

10 authors at 3 institutions in 1 country.

Henry C CousinsDepartment of Biomedical Data Science, Stanford University School of Medicine, Stanford, CA 94305, USA.
Adrienne Sarah KlineDepartment of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Chengkun WangDepartment of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Yuanhao QuDepartment of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
James ZengelDepartment of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Jan CaretteDepartment of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Mengdi WangDepartment of Electronic Engineering, Princeton University, Princeton, NJ 08544, USA.
Russ B AltmanDepartment of Biomedical Data Science, Stanford University School of Medicine, Stanford, CA 94305, USA.
Yuan LuoDepartment of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Le CongDepartment of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Stanford University · USNorthwestern University · USPrinceton University · US

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007365 · NIGMS · STANFORD UNIVERSITY · PI CHUA, KATRIN F · 1985 to 2021
$33.8M
Medical Scientist Training ProgramT32GM145402 · NIGMS · STANFORD UNIVERSITY · PI Katrin F. Chua · 2022 to 2026
$10.0M
Recombineering-based no-cleavage gene-editing toolkit for large-scale genome engineering and functional screeningR01GM141627 · NIGMS · STANFORD UNIVERSITY · PI Le Cong · 2021 to 2026
$3.3M
Undergraduate Summer Research Experiences Support for Combining systems biology and structural biology to find new therapeuticsR01GM102365 · NIGMS · STANFORD UNIVERSITY · PI ALTMAN, RUSS BIAGIO · 2012 to 2021
$3.0M
Towards Robust Multiplex Genome Engineering Beyond CRISPR-Cas9R35HG011316 · NHGRI · STANFORD UNIVERSITY · PI CONG, LE · 2020 to 2025
$2.8M
Modeling the Incompleteness and Biases of Health DataR01LM013337 · NLM · NORTHWESTERN UNIVERSITY AT CHICAGO · PI LUO, YUAN · 2020 to 2023
$1.3M
NHGRI NIH HHS R35 HG011316NIGMS NIH HHS R01 GM102365NIGMS NIH HHS R01 GM141627NIGMS NIH HHS T32 GM007365NIGMS NIH HHS T32 GM145402NLM NIH HHS R01 LM013337
6 · The paper itself

Abstract

We demonstrate that integrative analysis of CRISPR screening datasets enables network-based prioritization of prescription drugs modulating viral entry in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by developing a network-based approach called Rapid proXimity Guidance for Repurposing Investigational Drugs (RxGRID). We use our results to guide a propensity-score-matched, retrospective cohort study of 64,349 COVID-19 patients, showing that a top candidate drug, spironolactone, is associated with improved clinical prognosis, measured by intensive care unit (ICU) admission and mechanical ventilation rates. Finally, we show that spironolactone exerts a dose-dependent inhibitory effect on viral entry in human lung epithelial cells. Our RxGRID method presents a computational framework, implemented as an open-source software package, enabling genomics researchers to identify drugs likely to modulate a molecular phenotype of interest based on high-throughput screening data. Our results, derived from this method and supported by experimental and clinical analysis, add additional supporting evidence for a potential protective role of the potassium-sparing diuretic spironolactone in severe COVID-19.

Indexed as

COVID-19GenomicsHumansRetrospective StudiesSARS-CoV-2SpironolactoneSpironolactone

Identifiers

PMID37529368
PMCPMC10243122
OpenAlexW4378717155

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.