Evidence map›Paper›PMID 34475469›Full record

ArticleScientific reports2021

Evaluation of connectivity map shows limited reproducibility in drug repositioning.

Nathaniel Lim, Paul Pavlidis

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
4.7field-weighted citation impact, top 5% 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

33 citing papers in PubMed, 48 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

2 authors at 2 institutions in 1 country.

Nathaniel LimGenome Science and Technology Graduate Program, University of British Columbia, Vancouver, BC, V6T1Z4, Canada.
Paul PavlidisDepartment of Psychiatry, University of British Columbia, Vancouver, BC, V6T1Z4, Canada. paul@msl.ubc.ca.
Genome British Columbia · CAUniversity of British Columbia · CA

Funding

Neuroinformatics for gene expression: networks, function and meta-analysisR01MH111099 · NIMH · UNIVERSITY OF BRITISH COLUMBIA · PI PAVLIDIS, PAUL · 2016 to 2025
$3.6M
NIMH NIH HHS R01 MH111099
6 · The paper itself

Abstract

The Connectivity Map (CMap) is a popular resource designed for data-driven drug repositioning using a large transcriptomic compendium. However, evaluations of its performance are limited. We used two iterations of CMap (CMap 1 and 2) to assess their comparability and reliability. We queried CMap 2 with CMap 1-derived signatures, expecting CMap 2 would highly prioritize the queried compounds; the success rate was 17%. Analysis of previously published prioritizations yielded similar results. Low recall is caused by low differential expression (DE) reproducibility both between CMaps and within each CMap. DE strength was predictive of reproducibility, and is influenced by compound concentration and cell-line responsiveness. Reproducibility of CMap 2 sample expression levels was also lower than expected. We attempted to identify the "better" CMap by comparison with a third dataset, but they were mutually discordant. Our findings have implications for CMap usage and we suggest steps for investigators to limit false positives.

Indexed as

TranscriptomeDrug DiscoveryDrug RepositioningGene ExpressionHumans

Identifiers

PMID34475469
PMCPMC8413422
OpenAlexW3198724606

What Socratic 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 Socratic graph.