Identify Down syndrome transcriptome associations using integrative analysis of microarray database and correlation-interaction network
| Autor: | Allen M. Chen, Min Chen, Kailing Huang, Dunjin Chen, Jin Li, Shuya Xue, Liu Yanhui, Haimei Gao, Xiaoshun Shi, Yingjun Luo, Zhengfei Lai, Jiayan Wang |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
DSCR9 lcsh:QH426-470 Chromosomes Human Pair 21 Down syndrome Gene regulatory network lcsh:Medicine Computational biology Biology Correlation-interaction-network 03 medical and health sciences Genome Database lncRNA Interaction network Drug Discovery Genetics Microarray databases Humans Gene Regulatory Networks KEGG Molecular Biology Microarray analysis techniques Gene Expression Profiling lcsh:R Computational Biology Microarray Analysis Protein–protein interaction lcsh:Genetics 030104 developmental biology Gene Expression Regulation Molecular Medicine RNA Long Noncoding DNA microarray Chromosome 21 Transcriptome Biological network Neurological diseases Signal Transduction |
| Zdroj: | Human Genomics Human Genomics, Vol 12, Iss 1, Pp 1-12 (2018) |
| ISSN: | 1479-7364 1473-9542 |
| Popis: | Background Long non-coding RNAs (lncRNAs) have previously been emerged as key players in a series of biological processes. Dysregulation of lncRNA is correlated to human diseases including neurological disorders. Here, we developed a multi-step bioinformatics analysis to study the functions of a particular Down syndrome-associated gene DSCR9 including the lncRNAs. The method is named correlation-interaction-network (COIN), based on which a pipeline is implemented. Co-expression gene network analysis and biological network analysis results are presented. Methods We identified the regulation function of DSCR9, a lncRNA transcribed from the Down syndrome critical region (DSCR) of chromosome 21, by analyzing its co-expression genes from over 1700 sets and nearly 60,000 public Affymetrix human U133-Plus 2 transcriptional profiling microarrays. After proper evaluations, a threshold is chosen to filter the data and get satisfactory results. Microarray data resource is from EBI database and protein–protein interaction (PPI) network information is incorporated from the most complete network databases. PPI integration strategy guarantees complete information regarding DSCR9. Enrichment analysis is performed to identify significantly correlated pathways. Results We found that the most significant pathways associated with the top DSCR9 co-expressed genes were shown to be involved in neuro-active ligand-receptor interaction (GLP1R, HTR4, P2RX2, UCN3, and UTS2R), calcium signaling pathway (CACNA1F, CACNG4, HTR4, P2RX2, and SLC8A3), neuronal system (KCNJ5 and SYN1) by the KEGG, and GO analysis. The A549 and U251 cell lines with stable DSCR9 overexpression were constructed. We validated 10 DSCR9 co-expression genes by qPCR in both cell lines with over 70% accuracy. Conclusions DSCR9 was highly correlated with genes that were known as important factors in the developments and functions of nervous system, indicating that DSCR9 may regulate neurological proteins regarding Down syndrome and other neurological-related diseases. The pipeline can be properly adjusted to other applications. Electronic supplementary material The online version of this article (10.1186/s40246-018-0133-y) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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