Weighted gene co-expression network analysis of the peripheral blood from Amyotrophic Lateral Sclerosis patients

Saris, Christiaan G J; Horvath, Steve; Vught, Paul W.J. van; Es, Michael A. van; Blauw, Hylke M.; Fuller, Tova; Langfelder, Peter; DeYoung, Joseph; Wokke, John H. J.; Veldink, Jan H.; Berg, Leonard H van den; Ophoff, Roel A.

doi:10.1186/1471-2164-10-405

Cited by 153 publications

(152 citation statements)

References 70 publications

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“…11,23 In short, this dataset consists of 244 males and 193 females with a mean age of 62 years, who where recruited as controls in a study of gene expression in amyotrophic lateral sclerosis. These control subjects were selected for being in good general health and unaffected for neurological and neurodegenerative diseases; no separate screen for psychiatric disorders was performed for these subjects.…”

Section: Materials and Methods Eqtl Analysis In Controlsmentioning

confidence: 99%

Expression QTL analysis of top loci from GWAS meta-analysis highlights additional schizophrenia candidate genes

et al. 2012

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and The PGC Schizophrenia (GWAS) Consortium 7There is genetic evidence that schizophrenia is a polygenic disorder with a large number of loci of small effect on disease susceptibility. Genome-wide association studies (GWASs) of schizophrenia have had limited success, with the best finding at the MHC locus at chromosome 6p. A recent effort of the Psychiatric GWAS consortium (PGC) yielded five novel loci for schizophrenia. In this study, we aim to highlight additional schizophrenia susceptibility loci from the PGC study by combining the top association findings from the discovery stage (9394 schizophrenia cases and 12 462 controls) with expression QTLs (eQTLs) and differential gene expression in whole blood of schizophrenia patients and controls. We examined the 6192 singlenucleotide polymorphisms (SNPs) with significance threshold at Po0.001. eQTLs were calculated for these SNPs in a sample of healthy controls (n¼437). The transcripts significantly regulated by the top SNPs from the GWAS meta-analysis were subsequently tested for differential expression in an independent set of schizophrenia cases and controls (n¼202). After correction for multiple testing, the eQTL analysis yielded 40 significant cis-acting effects of the SNPs. Seven of these transcripts show differential expression between cases and controls. Of these, the effect of three genes (RNF5, TRIM26 and HLA-DRB3) coincided with the direction expected from meta-analysis findings and were all located within the MHC region. Our results identify new genes of interest and highlight again the involvement of the MHC region in schizophrenia susceptibility.

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Section: Materials and Methods Eqtl Analysis In Controlsmentioning

confidence: 99%

Expression QTL analysis of top loci from GWAS meta-analysis highlights additional schizophrenia candidate genes

et al. 2012

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“…Microarray analysis of SALS and control blood samples was followed by hierarchical clustering of all genes found to be significantly expressed in all samples after normalisation (Saris et al 2009). The method identified five clusters; two of which were able to differentiate between ALS and control samples.…”

Section: Results From Use Of Human Peripheral Tissuementioning

confidence: 99%

“…Gene expression profiling has been conducted on blood and fibroblasts from ALS patients (Highley et al 2011;Saris et al 2009;Zhang et al 2011). Microarray analysis of SALS and control blood samples was followed by hierarchical clustering of all genes found to be significantly expressed in all samples after normalisation (Saris et al 2009).…”

Section: Results From Use Of Human Peripheral Tissuementioning

confidence: 99%

“…Samples can be collected longitudinally, particularly as the collection of blood is relatively non-invasive and sampling techniques can be standardized across research centres (Highley et al 2011;Saris et al 2009;Shtilbans et al 2011;Tsuang et al 2005). Blood is classified as a fluid connective tissue composed of plasma (55%), erythrocytes (43%), leukocytes (0.5%) and platelets (1.5%) which continuously permeates and interacts with every other tissue and organ of the mammalian body.…”

Section: Human Peripheral Tissue Samplesmentioning

confidence: 99%

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Insights Arising from Gene Expression Profiling in Amyotrophic Lateral Sclerosis

Cooper‐Knock¹,

Bury²,

Ferraiuolo³

et al. 2012

Amyotrophic Lateral Sclerosis

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“…Co-expression methodology is typically used for explore correlation between gene expression level. Genes involved in the same pathway or same functional compound tend to demonstrate a similar expression pattern (15). Therefore, the construction of a gene co-expression network facilitates the identification of genes with similar biological functions (16).…”

Section: Construct Gene Co-expression Networkmentioning

confidence: 99%

Weighted gene co-expression network analysis in identification of metastasis-related genes of lung squamous cell carcinoma based on the Cancer Genome Atlas database

Tian¹,

Zhao²,

Xiu³

et al. 2017

J. Thorac. Dis.

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Background: Lung squamous cell carcinoma (lung SCC) is a common type of malignancy. Its pathogenesis mechanism of tumor development is unclear. The aim of this study was to identify key genes for diagnosis biomarkers in lung SCC metastasis. Methods: We searched and downloaded mRNA expression data and clinical data from The Cancer Genome Atlas (TCGA) database to identify differences in mRNA expression of primary tumor tissues from lung SCC with and without metastasis. Gene co-expression network analysis, protein-protein interaction (PPI) network, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and quantitative real-time polymerase chain reactions (qRT-PCR) were used to explore the biological functions of the identified dysregulated genes.Results: Four hundred and eighty-two differentially expressed genes (DEGs) were identified between lung SCC with and without metastasis. Nineteen modules were identified in lung SCC through weighted gene co-expression network analysis (WGCNA). Twenty-three DEGs and 26 DEGs were significantly enriched in the respective pink and black module. KEGG pathway analysis displayed that 26 DEGs in the black module were significantly enriched in bile secretion pathway. Forty-nine DEGs in the two gene co-expression module were used to construct PPI network. CFTR in the black module was the hub protein, had the connectivity with 182 genes. The results of qRT-PCR displayed that FIGF, SFTPD, DYNLRB2 were significantly down-regulated in the tumor samples of lung SCC with metastasis and CFTR, SCGB3A2, SSTR1, SCTR, ROPN1L had the down-regulation tendency in lung SCC with metastasis compared to lung SCC without metastasis. Conclusions: The dysregulated genes including CFTR, SCTR and FIGF might be involved in the pathology of lung SCC metastasis and could be used as potential diagnosis biomarkers or therapeutic targets for lung SCC. IntroductionLung squamous cell carcinoma (lung SCC) is a histological subtype of non-small cell lung cancer (NSCLC), which is the second most frequent type of NSCLC after lung adenocarcinoma (1). Lung SCC is a multi-step progressive disease with high rates of morbidity and mortality worldwide.The initiation of lung SCC is divided into the following five successive stages: normal bronchial epithelium, squamous metaplasia, mild-moderate dysplasia, carcinoma in situ, and invasive carcinoma (2). The prognosis of lung cancer is unfavorable, despite significant therapeutic improvements have been made in recent years. In current, there is no specific molecular targets for therapy have been identified (3), therefore, cisplatin plus gemcitabine is still the first-line treatment for lung SCC (4).Currently, the tumorigenesis mechanism of lung SCC remains unclear. Numerous published articles demonstrate that dysregulated genes are essential for initiation, progression and development of lung cancer. SMC4 (structural maintenance of chromosome 4) is over-expressed in lung adenocarcinoma tissues and its inhibition significantly suppresses the prolif...

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Weighted gene co-expression network analysis of the peripheral blood from Amyotrophic Lateral Sclerosis patients

Cited by 153 publications

References 70 publications

Expression QTL analysis of top loci from GWAS meta-analysis highlights additional schizophrenia candidate genes

Expression QTL analysis of top loci from GWAS meta-analysis highlights additional schizophrenia candidate genes

Insights Arising from Gene Expression Profiling in Amyotrophic Lateral Sclerosis

Weighted gene co-expression network analysis in identification of metastasis-related genes of lung squamous cell carcinoma based on the Cancer Genome Atlas database

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