Dataset Information

Potential Genes and Pathways of Neonatal Sepsis Based on Functional Gene Set Enrichment Analyses.

ABSTRACT: Background:Neonatal sepsis (NS) is considered as the most common cause of neonatal deaths that newborns suffer from. Although numerous studies focus on gene biomarkers of NS, the predictive value of the gene biomarkers is low. NS pathogenesis is still needed to be investigated. Methods:After data preprocessing, we used KEGG enrichment method to identify the differentially expressed pathways between NS and normal controls. Then, functional principal component analysis (FPCA) was adopted to calculate gene values in NS. In order to further study the key signaling pathway of the NS, elastic-net regression model, Mann-Whitney U test, and coexpression network were used to estimate the weights of signaling pathway and hub genes. Results:A total of 115 different pathways between NS and controls were first identified. FPCA made full use of time-series gene expression information and estimated F values of genes in the different pathways. The top 1000 genes were considered as the different genes and were further analyzed by elastic-net regression and MWU test. There were 7 key signaling pathways between the NS and controls, according to different sources. Among those genes involved in key pathways, 7 hub genes, PIK3CA, TGFBR2, CDKN1B, KRAS, E2F3, TRAF6, and CHUK, were determined based on the coexpression network. Most of them were cancer-related genes. PIK3CA was considered as the common marker, which is highly expressed in the lymphocyte group. Little was known about the correlation of PIK3CA with NS, which gives us a new enlightenment for NS study. Conclusion:This research might provide the perspective information to explore the potential novel genes and pathways as NS therapy targets.

SUBMITTER: Meng Y

PROVIDER: S-EPMC6091373 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Potential Genes and Pathways of Neonatal Sepsis Based on Functional Gene Set Enrichment Analyses.

Meng YuXiu Y Cai Xue Hong XH Wang LiPei L

Computational and mathematical methods in medicine 20180730

<h4>Background</h4>Neonatal sepsis (NS) is considered as the most common cause of neonatal deaths that newborns suffer from. Although numerous studies focus on gene biomarkers of NS, the predictive value of the gene biomarkers is low. NS pathogenesis is still needed to be investigated.<h4>Methods</h4>After data preprocessing, we used KEGG enrichment method to identify the differentially expressed pathways between NS and normal controls. Then, functional principal component analysis (FPCA) was ad ...[more]

PMID: 30154914

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Project description:Recent genome-wide association studies (GWAS) of chronic periodontitis (CP) offer rich data sources for the investigation of candidate genes, functional elements, and pathways. We used GWAS data of CP (n = 4,504) and periodontal pathogen colonization (n = 1,020) from a cohort of adult Americans of European descent participating in the Atherosclerosis Risk in Communities study and employed a MAGENTA approach (i.e., meta-analysis gene set enrichment of variant associations) to obtain gene-centric and gene set association results corrected for gene size, number of single-nucleotide polymorphisms, and local linkage disequilibrium characteristics based on the human genome build 18 (National Center for Biotechnology Information build 36). We used the Gene Ontology, Ingenuity, KEGG, Panther, Reactome, and Biocarta databases for gene set enrichment analyses. Six genes showed evidence of statistically significant association: 4 with severe CP (NIN, p = 1.6 × 10(-7); ABHD12B, p = 3.6 × 10(-7); WHAMM, p = 1.7 × 10(-6); AP3B2, p = 2.2 × 10(-6)) and 2 with high periodontal pathogen colonization (red complex-KCNK1, p = 3.4 × 10(-7); Porphyromonas gingivalis-DAB2IP, p = 1.0 × 10(-6)). Top-ranked genes for moderate CP were HGD (p = 1.4 × 10(-5)), ZNF675 (p = 1.5 × 10(-5)), TNFRSF10C (p = 2.0 × 10(-5)), and EMR1 (p = 2.0 × 10(-5)). Loci containing NIN, EMR1, KCNK1, and DAB2IP had showed suggestive evidence of association in the earlier single-nucleotide polymorphism-based analyses, whereas WHAMM and AP2B2 emerged as novel candidates. The top gene sets included severe CP ("endoplasmic reticulum membrane," "cytochrome P450," "microsome," and "oxidation reduction") and moderate CP ("regulation of gene expression," "zinc ion binding," "BMP signaling pathway," and "ruffle"). Gene-centric analyses offer a promising avenue for efficient interrogation of large-scale GWAS data. These results highlight genes in previously identified loci and new candidate genes and pathways possibly associated with CP, which will need to be validated via replication and mechanistic studies.

Dataset Information

Potential Genes and Pathways of Neonatal Sepsis Based on Functional Gene Set Enrichment Analyses.

Publications

Potential Genes and Pathways of Neonatal Sepsis Based on Functional Gene Set Enrichment Analyses.

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