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A meta-analysis of public microarray data identifies biological regulatory networks in Parkinson’s disease
BACKGROUND: Parkinson’s disease (PD) is a long-term degenerative disease that is caused by environmental and genetic factors. The networks of genes and their regulators that control the progression and development of PD require further elucidation. METHODS: We examine common differentially expressed...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5899355/ https://www.ncbi.nlm.nih.gov/pubmed/29653596 http://dx.doi.org/10.1186/s12920-018-0357-7 |
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author | Su, Lining Wang, Chunjie Zheng, Chenqing Wei, Huiping Song, Xiaoqing |
author_facet | Su, Lining Wang, Chunjie Zheng, Chenqing Wei, Huiping Song, Xiaoqing |
author_sort | Su, Lining |
collection | PubMed |
description | BACKGROUND: Parkinson’s disease (PD) is a long-term degenerative disease that is caused by environmental and genetic factors. The networks of genes and their regulators that control the progression and development of PD require further elucidation. METHODS: We examine common differentially expressed genes (DEGs) from several PD blood and substantia nigra (SN) microarray datasets by meta-analysis. Further we screen the PD-specific genes from common DEGs using GCBI. Next, we used a series of bioinformatics software to analyze the miRNAs, lncRNAs and SNPs associated with the common PD-specific genes, and then identify the mTF-miRNA-gene-gTF network. RESULT: Our results identified 36 common DEGs in PD blood studies and 17 common DEGs in PD SN studies, and five of the genes were previously known to be associated with PD. Further study of the regulatory miRNAs associated with the common PD-specific genes revealed 14 PD-specific miRNAs in our study. Analysis of the mTF-miRNA-gene-gTF network about PD-specific genes revealed two feed-forward loops: one involving the SPRK2 gene, hsa-miR-19a-3p and SPI1, and the second involving the SPRK2 gene, hsa-miR-17-3p and SPI. The long non-coding RNA (lncRNA)-mediated regulatory network identified lncRNAs associated with PD-specific genes and PD-specific miRNAs. Moreover, single nucleotide polymorphism (SNP) analysis of the PD-specific genes identified two significant SNPs, and SNP analysis of the neurodegenerative disease-specific genes identified seven significant SNPs. Most of these SNPs are present in the 3′-untranslated region of genes and are controlled by several miRNAs. CONCLUSION: Our study identified a total of 53 common DEGs in PD patients compared with healthy controls in blood and brain datasets and five of these genes were previously linked with PD. Regulatory network analysis identified PD-specific miRNAs, associated long non-coding RNA and feed-forward loops, which contribute to our understanding of the mechanisms underlying PD. The SNPs identified in our study can determine whether a genetic variant is associated with PD. Overall, these findings will help guide our study of the complex molecular mechanism of PD. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12920-018-0357-7) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5899355 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-58993552018-04-20 A meta-analysis of public microarray data identifies biological regulatory networks in Parkinson’s disease Su, Lining Wang, Chunjie Zheng, Chenqing Wei, Huiping Song, Xiaoqing BMC Med Genomics Research Article BACKGROUND: Parkinson’s disease (PD) is a long-term degenerative disease that is caused by environmental and genetic factors. The networks of genes and their regulators that control the progression and development of PD require further elucidation. METHODS: We examine common differentially expressed genes (DEGs) from several PD blood and substantia nigra (SN) microarray datasets by meta-analysis. Further we screen the PD-specific genes from common DEGs using GCBI. Next, we used a series of bioinformatics software to analyze the miRNAs, lncRNAs and SNPs associated with the common PD-specific genes, and then identify the mTF-miRNA-gene-gTF network. RESULT: Our results identified 36 common DEGs in PD blood studies and 17 common DEGs in PD SN studies, and five of the genes were previously known to be associated with PD. Further study of the regulatory miRNAs associated with the common PD-specific genes revealed 14 PD-specific miRNAs in our study. Analysis of the mTF-miRNA-gene-gTF network about PD-specific genes revealed two feed-forward loops: one involving the SPRK2 gene, hsa-miR-19a-3p and SPI1, and the second involving the SPRK2 gene, hsa-miR-17-3p and SPI. The long non-coding RNA (lncRNA)-mediated regulatory network identified lncRNAs associated with PD-specific genes and PD-specific miRNAs. Moreover, single nucleotide polymorphism (SNP) analysis of the PD-specific genes identified two significant SNPs, and SNP analysis of the neurodegenerative disease-specific genes identified seven significant SNPs. Most of these SNPs are present in the 3′-untranslated region of genes and are controlled by several miRNAs. CONCLUSION: Our study identified a total of 53 common DEGs in PD patients compared with healthy controls in blood and brain datasets and five of these genes were previously linked with PD. Regulatory network analysis identified PD-specific miRNAs, associated long non-coding RNA and feed-forward loops, which contribute to our understanding of the mechanisms underlying PD. The SNPs identified in our study can determine whether a genetic variant is associated with PD. Overall, these findings will help guide our study of the complex molecular mechanism of PD. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12920-018-0357-7) contains supplementary material, which is available to authorized users. BioMed Central 2018-04-13 /pmc/articles/PMC5899355/ /pubmed/29653596 http://dx.doi.org/10.1186/s12920-018-0357-7 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Su, Lining Wang, Chunjie Zheng, Chenqing Wei, Huiping Song, Xiaoqing A meta-analysis of public microarray data identifies biological regulatory networks in Parkinson’s disease |
title | A meta-analysis of public microarray data identifies biological regulatory networks in Parkinson’s disease |
title_full | A meta-analysis of public microarray data identifies biological regulatory networks in Parkinson’s disease |
title_fullStr | A meta-analysis of public microarray data identifies biological regulatory networks in Parkinson’s disease |
title_full_unstemmed | A meta-analysis of public microarray data identifies biological regulatory networks in Parkinson’s disease |
title_short | A meta-analysis of public microarray data identifies biological regulatory networks in Parkinson’s disease |
title_sort | meta-analysis of public microarray data identifies biological regulatory networks in parkinson’s disease |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5899355/ https://www.ncbi.nlm.nih.gov/pubmed/29653596 http://dx.doi.org/10.1186/s12920-018-0357-7 |
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