Evidence map›Paper›PMID 37689782›Full record

ArticleNature communications2023

Projecting genetic associations through gene expression patterns highlights disease etiology and drug mechanisms.

Milton Pividori, Sumei Lu, Binglan Li, Chun Su, Matthew E Johnson, Wei-Qi Wei, Qiping Feng, Bahram Namjou, Krzysztof Kiryluk, Iftikhar J Kullo and 8 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
3.4field-weighted citation impact, top 7% 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

22 citing papers in PubMed, 22 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. PLIERv2: bigger, better and faster.bioRxiv : the preprint server for biology · 2025
    Article
  10. Review
  11. Article
  12. Article
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  15. Article
  16. Article
  17. A publishing infrastructure for Artificial Intelligence (AI)-assisted academic authoring.Journal of the American Medical Informatics Association : JAMIA · 2024
    Article
  18. Article
  19. BuDDI:bioRxiv : the preprint server for biology · 2024
    Article
  20. Meta-Learning on Augmented Gene Expression Profiles for Enhanced Lung Cancer Detection.AMIA ... Annual Symposium proceedings. AMIA Symposium · 2024
    Article
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

18 authors at 11 institutions in 1 country.

Milton PividoriDepartment of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.ORCID http://orcid.org/0000-0002-3035-4403
Sumei LuCenter for Spatial and Functional Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.
Binglan LiDepartment of Biomedical Data Science, Stanford University, Stanford, CA, 94305, USA.ORCID http://orcid.org/0000-0002-0103-6107
Chun SuCenter for Spatial and Functional Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.
Matthew E JohnsonCenter for Spatial and Functional Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.
Wei-Qi WeiVanderbilt University Medical Center, Nashville, TN, 37232, USA.ORCID http://orcid.org/0000-0003-4985-056X
Qiping FengVanderbilt University Medical Center, Nashville, TN, 37232, USA.ORCID http://orcid.org/0000-0002-6213-793X
Bahram NamjouCincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA.ORCID http://orcid.org/0000-0003-4452-7878
Krzysztof KirylukDepartment of Medicine, Division of Nephrology, Vagelos College of Physicians & Surgeons, Columbia University, New York, NY, 10032, USA.
Iftikhar J KulloMayo Clinic, Rochester, MN, 55905, USA.ORCID http://orcid.org/0000-0002-6524-3471
Yuan LuoNorthwestern University, Chicago, IL, 60611, USA.ORCID http://orcid.org/0000-0003-0195-7456
Blair D SullivanKahlert School of Computing, University of Utah, Salt Lake City, UT, 84112, USA.ORCID http://orcid.org/0000-0001-7720-6208
Benjamin F VoightDepartment of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.ORCID http://orcid.org/0000-0002-6205-9994
Carsten SkarkeInstitute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.ORCID http://orcid.org/0000-0001-5145-3681
Marylyn D RitchieDepartment of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.ORCID http://orcid.org/0000-0002-1208-1720
Struan F A GrantDepartment of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.ORCID http://orcid.org/0000-0003-2025-5302
eMERGE Consortium
Casey S GreeneDepartment of Biomedical Informatics, University of Colorado School of Medicine, Aurora, CO, 80045, USA. casey.s.greene@cuanschutz.edu.ORCID http://orcid.org/0000-0001-8713-9213
Children's Hospital of Philadelphia · USTranslational Therapeutics (United States) · USUniversity of Pennsylvania · USVanderbilt University Medical Center · USCincinnati Children's Hospital Medical Center · USColumbia University · USMayo Clinic in Arizona · USNorthwestern University · USStanford University · USUniversity of Colorado Anschutz Medical Campus · USUniversity of Utah · US

Funding

Phenotypic Diversity in COVID-19UL1TR001878 · NCATS · UNIVERSITY OF PENNSYLVANIA · PI FITZGERALD, GARRET A · 2016 to 2025
$102.4M
Genomic Basis of Susceptibility to COVID-19 Infection and its ComplicationsU01HG006379 · NHGRI · MAYO CLINIC ROCHESTER · PI Richard R. Sharp · 2011 to 2026
$16.5M
Finding Genomic Profiles of COVID-19 Phenotypes from the EHRU01HG008685 · NHGRI · BRIGHAM AND WOMEN'S HOSPITAL · PI ELIZABETH W KARLSON, Matthew S Lebo · 2015 to 2026
$13.6M
Variation, Function, and Disease Supplement ProgramU01HG008657 · NHGRI · UNIVERSITY OF WASHINGTON · PI David Russell Crosslin, Gail Pairitz Jarvik · 2015 to 2026
$13.4M
OMOP information model for eMERGE phenotypingU01HG008680 · NHGRI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Wendy K Chung, GEORGE M HRIPCSAK · 2015 to 2026
$13.3M
DNA Sequencing Support for the eMERGE NetworkU01HG008664 · NHGRI · BAYLOR COLLEGE OF MEDICINE · PI GIBBS, RICHARD A · 2015 to 2019
$10.9M
Research Design, Data, and Analytics CoreP30DK092949 · NIDDK · UNIVERSITY OF CHICAGO · PI Ronald T. Ackermann, MARSHALL H CHIN · 2011 to 2026
$10.0M
Functional Interrogation of T2D-associated genes in human stem cell-derived models and miceUM1DK126194 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI GRANT, STRUAN F A, KAESTNER, KLAUS H · 2020 to 2024
$8.8M
Global Alliance for Genomic Health (GA4GH)U01HG008676 · NHGRI · BRIGHAM AND WOMEN'S HOSPITAL · PI LENNON, NIALL JOHN, REHM, HEIDI L · 2015 to 2019
$8.6M
Polygenic Risk Scores for Healthier African American FamiliesU01HG011172 · NHGRI · CINCINNATI CHILDRENS HOSP MED CTR · PI Leah Claire Kottyan, LISA J MARTIN · 2020 to 2026
$7.2M
The Electronic Medical Records and Genomics (eMERGE) Network Phase III Coordinating Center (U01)U01HG008701 · NHGRI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI PETERSON, JOSEPH F. · 2015 to 2019
$7.1M
Vanderbilt Genome-Electronic Records (VGER) ProjectU01HG011181 · NHGRI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI DAN M RODEN, Digna R Velez Edwards · 2020 to 2026
$7.0M
NCATS NIH HHS UL1 TR001878NCI NIH HHS R01 CA237170NHGRI NIH HHS K99 HG011898NHGRI NIH HHS R00 HG011898NHGRI NIH HHS R01 HG010067NHGRI NIH HHS U01 HG006379NHGRI NIH HHS U01 HG008657NHGRI NIH HHS U01 HG008664NHGRI NIH HHS U01 HG008666NHGRI NIH HHS U01 HG008672NHGRI NIH HHS U01 HG008673NHGRI NIH HHS U01 HG008676NHGRI NIH HHS U01 HG008679NHGRI NIH HHS U01 HG008680NHGRI NIH HHS U01 HG008684NHGRI NIH HHS U01 HG008685NHGRI NIH HHS U01 HG008701NHGRI NIH HHS U01 HG011172NHGRI NIH HHS U01 HG011181NHLBI NIH HHS R01 HL163854NIA NIH HHS R01 AG069900NICHD NIH HHS R01 HD109765NIDDK NIH HHS P30 DK092949NIDDK NIH HHS R56 DK101478NIDDK NIH HHS UM1 DK126194NIGMS NIH HHS R01 GM139891
6 · The paper itself

Abstract

Genes act in concert with each other in specific contexts to perform their functions. Determining how these genes influence complex traits requires a mechanistic understanding of expression regulation across different conditions. It has been shown that this insight is critical for developing new therapies. Transcriptome-wide association studies have helped uncover the role of individual genes in disease-relevant mechanisms. However, modern models of the architecture of complex traits predict that gene-gene interactions play a crucial role in disease origin and progression. Here we introduce PhenoPLIER, a computational approach that maps gene-trait associations and pharmacological perturbation data into a common latent representation for a joint analysis. This representation is based on modules of genes with similar expression patterns across the same conditions. We observe that diseases are significantly associated with gene modules expressed in relevant cell types, and our approach is accurate in predicting known drug-disease pairs and inferring mechanisms of action. Furthermore, using a CRISPR screen to analyze lipid regulation, we find that functionally important players lack associations but are prioritized in trait-associated modules by PhenoPLIER. By incorporating groups of co-expressed genes, PhenoPLIER can contextualize genetic associations and reveal potential targets missed by single-gene strategies.

Indexed as

Clustered Regularly Interspaced Short Palindromic RepeatsEpistasis, GeneticCausalityGene Regulatory NetworksTranscriptome

Identifiers

PMID37689782
PMCPMC10492839
OpenAlexW4386574639

What OpenQuestion holds

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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 OpenQuestion graph.