Evidence map›Paper›PMID 28081703›Full record

ArticleBMC pulmonary medicine2017

Identification and validation of differentially expressed transcripts by RNA-sequencing of formalin-fixed, paraffin-embedded (FFPE) lung tissue from patients with Idiopathic Pulmonary Fibrosis.

Milica Vukmirovic, Jose D Herazo-Maya, John Blackmon, Vesna Skodric-Trifunovic, Dragana Jovanovic, Sonja Pavlovic, Jelena Stojsic, Vesna Zeljkovic, Xiting Yan, Robert Homer and 2 more

Open access · goldAbstract readComparative StudyValidation Study
In one paragraph

Article in BMC pulmonary medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed, 1 pooled it
7.2field-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

42 citing papers in PubMed, 1 synthesis or guideline pooled it, 70 citations in OpenAlex.

  1. Pooled it
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  6. hLife · 2024
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  15. Transcriptomic and Epigenetic Profiling of Fibroblasts in Idiopathic Pulmonary Fibrosis.American journal of respiratory cell and molecular biology · 2022
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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

12 authors at 5 institutions in 2 countries.

Milica VukmirovicSection of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, CT, USA. milica.vukmirovic@yale.edu.ORCID 0000-0002-2025-3887
Jose D Herazo-MayaSection of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, CT, USA.
John BlackmonDepartment of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, FL, USA.
Vesna Skodric-TrifunovicFaculty of Medicine, University of Belgrade, Belgrade, Serbia.
Dragana JovanovicFaculty of Medicine, University of Belgrade, Belgrade, Serbia.
Sonja PavlovicInstitute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
Jelena StojsicDepartement of Thoracopulmonary Pathology, Service of Pathology, Clinical Centre of Serbia, Belgrade, Serbia.
Vesna ZeljkovicFaculty of Medicine, University of Novi Sad, Novi Sad, Serbia.
Xiting YanSection of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, CT, USA.
Robert HomerDepartment of Pathology, Yale University School of Medicine, New Haven, CT, USA.
Branko StefanovicDepartment of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, FL, USA.
Naftali KaminskiSection of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, CT, USA.
Yale University · USUniversity of Belgrade · RSFlorida State University · USCentar za Promociju Nauke · RSUniversity of Novi Sad · RS

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Institutional Career Development CoreKL2TR001862 · NCATS · YALE UNIVERSITY · PI CANTLEY, LLOYD G, EDELMAN, E. JENNIFER · 2016 to 2025
$12.2M
Genomic Analysis of Tissue and Cellular Heterogeneity in IPFR01HL127349 · NHLBI · YALE UNIVERSITY · PI BENOS, PANAGIOTIS V, KAMINSKI, NAFTALI · 2015 to 2025
$5.9M
NCATS NIH HHS KL2 TR001862NCATS NIH HHS UL1 TR001863NHLBI NIH HHS R01 HL127349
6 · The paper itself

Abstract

backgroundIdiopathic Pulmonary Fibrosis (IPF) is a lethal lung disease of unknown etiology. A major limitation in transcriptomic profiling of lung tissue in IPF has been a dependence on snap-frozen fresh tissues (FF). In this project we sought to determine whether genome scale transcript profiling using RNA Sequencing (RNA-Seq) could be applied to archived Formalin-Fixed Paraffin-Embedded (FFPE) IPF tissues.

resultsWe isolated total RNA from 7 IPF and 5 control FFPE lung tissues and performed 50 base pair paired-end sequencing on Illumina 2000 HiSeq. TopHat2 was used to map sequencing reads to the human genome. On average ~62 million reads (53.4% of ~116 million reads) were mapped per sample. 4,131 genes were differentially expressed between IPF and controls (1,920 increased and 2,211 decreased (FDR < 0.05). We compared our results to differentially expressed genes calculated from a previously published dataset generated from FF tissues analyzed on Agilent microarrays (GSE47460). The overlap of differentially expressed genes was very high (760 increased and 1,413 decreased, FDR < 0.05). Only 92 differentially expressed genes changed in opposite directions. Pathway enrichment analysis performed using MetaCore confirmed numerous IPF relevant genes and pathways including extracellular remodeling, TGF-beta, and WNT. Gene network analysis of MMP7, a highly differentially expressed gene in both datasets, revealed the same canonical pathways and gene network candidates in RNA-Seq and microarray data. For validation by NanoString nCounter® we selected 35 genes that had a fold change of 2 in at least one dataset (10 discordant, 10 significantly differentially expressed in one dataset only and 15 concordant genes). High concordance of fold change and FDR was observed for each type of the samples (FF vs FFPE) with both microarrays (r = 0.92) and RNA-Seq (r = 0.90) and the number of discordant genes was reduced to four.

conclusionsOur results demonstrate that RNA sequencing of RNA obtained from archived FFPE lung tissues is feasible. The results obtained from FFPE tissue are highly comparable to FF tissues. The ability to perform RNA-Seq on archived FFPE IPF tissues should greatly enhance the availability of tissue biopsies for research in IPF.

Indexed as

Gene Expression ProfilingCase-Control StudiesChildFreezingGene Regulatory NetworksHumansIdiopathic Pulmonary FibrosisLungMatrix Metalloproteinase 7Microarray AnalysisParaffin EmbeddingRNASequence Analysis, RNAUnited StatesWnt Signaling PathwayMatrix Metalloproteinase 7MMP7 protein, humanRNADEGsFFPEIdiopathic Pulmonary FibrosisMicroarrayMMP7NanoString nCounter®NetworkPathwaysRNA-SeqValidation

Identifiers

PMID28081703
PMCPMC5228096
OpenAlexW2571895431

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.