BibTex format
@article{Kraven:2022:10.1136/thoraxjnl-2021-218563,
author = {Kraven, LM and Taylor, AR and Molyneaux, PL and Maher, T and McDonough, J and Mura, M and Yang, I and Schwartz, DA and Huang, Y and Noth, I and Ma, SF and Yeo, AJ and Fahy, WA and Jenkins, G and Wain, L},
doi = {10.1136/thoraxjnl-2021-218563},
journal = {Thorax},
pages = {551--558},
title = {Cluster analysis of transcriptomic datasets to identify endotypes of idiopathic pulmonary fibrosis},
url = {http://dx.doi.org/10.1136/thoraxjnl-2021-218563},
volume = {78},
year = {2022}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - Background Considerable clinical heterogeneity in idiopathic pulmonary fibrosis (IPF) suggests the existence of multiple disease endotypes. Identifying these endotypes would improve our understanding of the pathogenesis of IPF and could allow for a biomarker-driven personalised medicine approach. We aimed to identify clinically distinct groups of patients with IPF that could represent distinct disease endotypes.Methods We co-normalised, pooled and clustered three publicly available blood transcriptomic datasets (total 220 IPF cases). We compared clinical traits across clusters and used gene enrichment analysis to identify biological pathways and processes that were over-represented among the genes that were differentially expressed across clusters. A gene-based classifier was developed and validated using three additional independent datasets (total 194 IPF cases).Findings We identified three clusters of patients with IPF with statistically significant differences in lung function (p=0.009) and mortality (p=0.009) between groups. Gene enrichment analysis implicated mitochondrial homeostasis, apoptosis, cell cycle and innate and adaptive immunity in the pathogenesis underlying these groups. We developed and validated a 13-gene cluster classifier that predicted mortality in IPF (high-risk clusters vs low-risk cluster: HR 4.25, 95% CI 2.14 to 8.46, p=3.7×10−5).Interpretation We have identified blood gene expression signatures capable of discerning groups of patients with IPF with significant differences in survival. These clusters could be representative of distinct pathophysiological states, which would support the theory of multiple endotypes of IPF. Although more work must be done to confirm the existence of these endotypes, our classifier could be a useful tool in patient stratification and outcome prediction in IPF.
AU - Kraven,LM
AU - Taylor,AR
AU - Molyneaux,PL
AU - Maher,T
AU - McDonough,J
AU - Mura,M
AU - Yang,I
AU - Schwartz,DA
AU - Huang,Y
AU - Noth,I
AU - Ma,SF
AU - Yeo,AJ
AU - Fahy,WA
AU - Jenkins,G
AU - Wain,L
DO - 10.1136/thoraxjnl-2021-218563
EP - 558
PY - 2022///
SN - 0040-6376
SP - 551
TI - Cluster analysis of transcriptomic datasets to identify endotypes of idiopathic pulmonary fibrosis
T2 - Thorax
UR - http://dx.doi.org/10.1136/thoraxjnl-2021-218563
UR - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000793334900001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR - http://hdl.handle.net/10044/1/97070
VL - 78
ER -