Evidence map›Paper›PMID 20885780›Full record

ArticlePLoS computational biology2010

Differentially expressed RNA from public microarray data identifies serum protein biomarkers for cross-organ transplant rejection and other conditions.

Rong Chen, Tara K Sigdel, Li Li, Neeraja Kambham, Joel T Dudley, Szu-Chuan Hsieh, R Bryan Klassen, Amery Chen, Tuyen Caohuu, Alexander A Morgan and 4 more

Open access · goldAbstract read
In one paragraph

Article in PLoS computational biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed, 2 pooled it
9.8field-weighted citation impact, top 2% 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

40 citing papers in PubMed, 2 syntheses or guidelines pooled it, 81 citations in OpenAlex.

  1. Pooled it
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  16. Advances in diagnostics for transplant rejection.Expert review of molecular diagnostics · 2016
    Review
  17. Gene Expression in Biopsies of Acute Rejection and Interstitial Fibrosis/Tubular Atrophy Reveals Highly Shared Mechanisms That Correlate With Worse Long-Term Outcomes.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2016
    Article
  18. Data standards can boost metabolomics research, and if there is a will, there is a way.Metabolomics : Official journal of the Metabolomic Society · 2016
    Review
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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

14 authors at 2 institutions in 1 country.

Rong ChenDepartment of Pediatrics, Stanford University School of Medicine, Stanford, California, United States of America.
Tara K Sigdel
Li Li
Neeraja Kambham
Joel T Dudley
Szu-Chuan Hsieh
R Bryan Klassen
Amery Chen
Tuyen Caohuu
Alexander A Morgan
Hannah A Valantine
Kiran K Khush
Minnie M Sarwal
Atul J Butte
Stanford University · USLucile Packard Children's Hospital · US

Funding

POSTDOCTORAL TRAINING IN MEDICAL INFORMATION SCIENCEST15LM007033 · NLM · STANFORD UNIVERSITY · PI SYLVIA KATINA PLEVRITIS · 1985 to 2026
$25.5M
Repositioning drugs for the treatment of small cell lung cancerR01GM079719 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BUTTE, ATUL J · 2006 to 2015
$4.4M
Integrating Microarray and Proteomic Data by Ontology-based AnnotationR01LM009719 · NLM · STANFORD UNIVERSITY · PI BUTTE, ATUL J · 2008 to 2011
$1.1M
Howard Hughes Medical InstituteNIGMS NIH HHS R01 GM079719NLM NIH HHS R01 LM009719NLM NIH HHS T15 LM007033
6 · The paper itself

Abstract

Serum proteins are routinely used to diagnose diseases, but are hard to find due to low sensitivity in screening the serum proteome. Public repositories of microarray data, such as the Gene Expression Omnibus (GEO), contain RNA expression profiles for more than 16,000 biological conditions, covering more than 30% of United States mortality. We hypothesized that genes coding for serum- and urine-detectable proteins, and showing differential expression of RNA in disease-damaged tissues would make ideal diagnostic protein biomarkers for those diseases. We showed that predicted protein biomarkers are significantly enriched for known diagnostic protein biomarkers in 22 diseases, with enrichment significantly higher in diseases for which at least three datasets are available. We then used this strategy to search for new biomarkers indicating acute rejection (AR) across different types of transplanted solid organs. We integrated three biopsy-based microarray studies of AR from pediatric renal, adult renal and adult cardiac transplantation and identified 45 genes upregulated in all three. From this set, we chose 10 proteins for serum ELISA assays in 39 renal transplant patients, and discovered three that were significantly higher in AR. Interestingly, all three proteins were also significantly higher during AR in the 63 cardiac transplant recipients studied. Our best marker, serum PECAM1, identified renal AR with 89% sensitivity and 75% specificity, and also showed increased expression in AR by immunohistochemistry in renal, hepatic and cardiac transplant biopsies. Our results demonstrate that integrating gene expression microarray measurements from disease samples and even publicly-available data sets can be a powerful, fast, and cost-effective strategy for the discovery of new diagnostic serum protein biomarkers.

Indexed as

BiomarkersBlood ProteinsComputational BiologyDatabases, GeneticData MiningEnzyme-Linked Immunosorbent AssayGene Expression ProfilingGraft RejectionHeart TransplantationHistocytochemistryHumansKidney GlomerulusKidney TransplantationOligonucleotide Array Sequence AnalysisProteinuriaReproducibility of ResultsBiomarkersBlood ProteinsRNA

Identifiers

PMID20885780
PMCPMC2944782
OpenAlexW2011810052

What OpenQuestion 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 OpenQuestion graph.