Dataset Information

Identify Down syndrome transcriptome associations using integrative analysis of microarray database and correlation-interaction network.

ABSTRACT: 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.

SUBMITTER: Chen M

PROVIDER: S-EPMC5775600 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Identify Down syndrome transcriptome associations using integrative analysis of microarray database and correlation-interaction network.

Chen Min M Wang Jiayan J Luo Yingjun Y Huang Kailing K Shi Xiaoshun X Liu Yanhui Y Li Jin J Lai Zhengfei Z Xue Shuya S Gao Haimei H Chen Allen A Chen Dunjin D

Human genomics 20180119 1

<h4>Background</h4>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 netw ...[more]

PMID: 29351810

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Project description:BACKGROUND: With the emergence of a completed genome sequence of the freshwater crustacean Daphnia pulex, construction of genomic-scale sequence databases for additional crustacean sequences are important for comparative genomics and annotation. Porcelain crabs, genus Petrolisthes, have been powerful crustacean models for environmental and evolutionary physiology with respect to thermal adaptation and understanding responses of marine organisms to climate change. Here, we present a large-scale EST sequencing and cDNA microarray database project for the porcelain crab Petrolisthes cinctipes. METHODOLOGY/PRINCIPAL FINDINGS: A set of approximately 30K unique sequences (UniSeqs) representing approximately 19K clusters were generated from approximately 98K high quality ESTs from a set of tissue specific non-normalized and mixed-tissue normalized cDNA libraries from the porcelain crab Petrolisthes cinctipes. Homology for each UniSeq was assessed using BLAST, InterProScan, GO and KEGG database searches. Approximately 66% of the UniSeqs had homology in at least one of the databases. All EST and UniSeq sequences along with annotation results and coordinated cDNA microarray datasets have been made publicly accessible at the Porcelain Crab Array Database (PCAD), a feature-enriched version of the Stanford and Longhorn Array Databases. CONCLUSIONS/SIGNIFICANCE: The EST project presented here represents the third largest sequencing effort for any crustacean, and the largest effort for any crab species. Our assembly and clustering results suggest that our porcelain crab EST data set is equally diverse to the much larger EST set generated in the Daphnia pulex genome sequencing project, and thus will be an important resource to the Daphnia research community. Our homology results support the pancrustacea hypothesis and suggest that Malacostraca may be ancestral to Branchiopoda and Hexapoda. Our results also suggest that our cDNA microarrays cover as much of the transcriptome as can reasonably be captured in EST library sequencing approaches, and thus represent a rich resource for studies of environmental genomics.

Dataset Information

Identify Down syndrome transcriptome associations using integrative analysis of microarray database and correlation-interaction network.

Publications

Identify Down syndrome transcriptome associations using integrative analysis of microarray database and correlation-interaction network.

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