Evidence map›Paper›PMID 34529084›Full record

ArticleJournal of the American Medical Informatics Association : JAMIA2021

Computational drug repositioning of atorvastatin for ulcerative colitis.

Lawrence Bai, Madeleine K D Scott, Ethan Steinberg, Laurynas Kalesinskas, Aida Habtezion, Nigam H Shah, Purvesh Khatri

Open access · hybridAbstract read
In one paragraph

Article in Journal of the American Medical Informatics Association : JAMIA, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed, 1 pooled it
3.8field-weighted citation impact, top 6% 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

21 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.

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  15. International journal of molecular sciences · 2024
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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

7 authors at 1 institution in 1 country.

Lawrence BaiImmunology Program, Stanford University School of Medicine, Stanford, California, USA.ORCID 0000-0002-5617-9025
Madeleine K D ScottInstitute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, California, USA.
Ethan SteinbergComputer Science Program, Department of Computer Science, Stanford University, Stanford, California, USA.
Laurynas KalesinskasBiomedical Informatics Training Program, Stanford University School of Medicine, Stanford, California, USA.
Aida HabtezionImmunology Program, Stanford University School of Medicine, Stanford, California, USA.
Nigam H ShahCenter for Biomedical Informatics Research, Department of Medicine, Stanford University, Stanford, California, USA.ORCID 0000-0001-9385-7158
Purvesh KhatriInstitute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, California, USA.ORCID 0000-0002-4143-4708
Stanford University · US

Funding

Using a tonsil organoid system to probe conditions for the induction of protective antibody and T cell responses to influenza.U19AI057229 · NIAID · STANFORD UNIVERSITY · PI Mark Morris Davis · 2003 to 2026
$88.5M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007365 · NIGMS · STANFORD UNIVERSITY · PI CHUA, KATRIN F · 1985 to 2021
$33.8M
Translational Incubator CoreU19AI109662 · NIAID · STANFORD UNIVERSITY · PI GLENN, JEFFREY S · 2014 to 2019
$28.6M
MOLECULAR &CELLULAR IMMUNOBIOLOGYT32AI007290 · NIAID · STANFORD UNIVERSITY · PI Sean Curtis Bendall, Olivia M Martinez · 1985 to 2026
$27.0M
Giant MagnetoResistive (GMR) Sensors for Measuring Influenza VaccineR01AI125197 · NIAID · STANFORD UNIVERSITY · PI UTZ, PAUL JOSEPH, WANG, SHAN X. · 2016 to 2021
$5.0M
Gates Foundation OPP1113682NIAID NIH HHS 1U19AI109662NIAID NIH HHS R01 AI125197NIAID NIH HHS T32 AI007290NIAID NIH HHS U19 AI057229NIAID NIH HHS U19 AI109662NIGMS NIH HHS T32 GM007365NIH HHS T32GM007365
6 · The paper itself

Abstract

objectiveUlcerative colitis (UC) is a chronic inflammatory disorder with limited effective therapeutic options for long-term treatment and disease maintenance. We hypothesized that a multi-cohort analysis of independent cohorts representing real-world heterogeneity of UC would identify a robust transcriptomic signature to improve identification of FDA-approved drugs that can be repurposed to treat patients with UC. MATERIALS AND

methodsWe performed a multi-cohort analysis of 272 colon biopsy transcriptome samples across 11 publicly available datasets to identify a robust UC disease gene signature. We compared the gene signature to in vitro transcriptomic profiles induced by 781 FDA-approved drugs to identify potential drug targets. We used a retrospective cohort study design modeled after a target trial to evaluate the protective effect of predicted drugs on colectomy risk in patients with UC from the Stanford Research Repository (STARR) database and Optum Clinformatics DataMart.

resultsAtorvastatin treatment had the highest inverse-correlation with the UC gene signature among non-oncolytic FDA-approved therapies. In both STARR (n = 827) and Optum (n = 7821), atorvastatin intake was significantly associated with a decreased risk of colectomy, a marker of treatment-refractory disease, compared to patients prescribed a comparator drug (STARR: HR = 0.47, P = .03; Optum: HR = 0.66, P = .03), irrespective of age and length of atorvastatin treatment. DISCUSSION &

conclusionThese findings suggest that atorvastatin may serve as a novel therapeutic option for ameliorating disease in patients with UC. Importantly, we provide a systematic framework for integrating publicly available heterogeneous molecular data with clinical data at a large scale to repurpose existing FDA-approved drugs for a wide range of human diseases.

Indexed as

Colitis, UlcerativeAtorvastatinColectomyDrug RepositioningHumansRetrospective StudiesAtorvastatindrug repurposinggene expressionmulti-cohort analysis, ulcerative colitis, electronic health recordstranscriptomics

Identifiers

PMID34529084
PMCPMC8510297
OpenAlexW3201381398

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.