Nance, T and Smith, KS and Anaya, V and Richardson, R and Ho, L and Pala, M and Mostafavi, S and Battle, A and Feghali-Bostwick, C and Rosen, G and Montgomery, SB
(2014)
Transcriptome analysis reveals differential splicing events in IPF lung tissue.
PLoS ONE, 9 (3).
Abstract
Idiopathic pulmonary fibrosis (IPF) is a complex disease in which a multitude of proteins and networks are disrupted. Interrogation of the transcriptome through RNA sequencing (RNA-Seq) enables the determination of genes whose differential expression is most significant in IPF, as well as the detection of alternative splicing events which are not easily observed with traditional microarray experiments. We sequenced messenger RNA from 8 IPF lung samples and 7 healthy controls on an Illumina HiSeq 2000, and found evidence for substantial differential gene expression and differential splicing. 873 genes were differentially expressed in IPF (FDR<5%), and 440 unique genes had significant differential splicing events in at least one exonic region (FDR<5%). We used qPCR to validate the differential exon usage in the second and third most significant exonic regions, in the genes COL6A3 (RNA-Seq adjusted pval = 7.18e-10) and POSTN (RNA-Seq adjusted pval = 2.06e-09), which encode the extracellular matrix proteins collagen alpha-3(VI) and periostin. The increased gene-level expression of periostin has been associated with IPF and its clinical progression, but its differential splicing has not been studied in the context of this disease. Our results suggest that alternative splicing of these and other genes may be involved in the pathogenesis of IPF. We have developed an interactive web application which allows users to explore the results of our RNA-Seq experiment, as well as those of two previously published microarray experiments, and we hope that this will serve as a resource for future investigations of gene regulation in IPF. © 2014 Nance et al.
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| Item Type: |
Article
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| Status: |
Published |
| Creators/Authors: |
| Creators | Email | Pitt Username | ORCID  |
|---|
| Nance, T | | | | | Smith, KS | | | | | Anaya, V | | | | | Richardson, R | | | | | Ho, L | | | | | Pala, M | | | | | Mostafavi, S | | | | | Battle, A | | | | | Feghali-Bostwick, C | | | | | Rosen, G | | | | | Montgomery, SB | | | |
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| Contributors: |
| Contribution | Contributors Name | Email | Pitt Username | ORCID |
|---|
| Editor | Buratti, Emanuele | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED |
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| Date: |
19 March 2014 |
| Date Type: |
Publication |
| Journal or Publication Title: |
PLoS ONE |
| Volume: |
9 |
| Number: |
3 |
| DOI or Unique Handle: |
10.1371/journal.pone.0092111 |
| Schools and Programs: |
School of Medicine > Medicine |
| Refereed: |
Yes |
| Date Deposited: |
30 Jun 2014 15:58 |
| Last Modified: |
20 Dec 2018 00:55 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/21948 |
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