Modular genome-wide gene expression architecture shared by early traits of osteoporosis and atherosclerosis in the Young Finns Study

AbstractWe analysed whole blood genome-wide expression data to identify gene co-expression modules shared by early traits of osteoporosis and atherosclerosis. Gene expression was profiled for the Young Finns Study participants. Bone mineral density and content were measured as early traits of osteoporosis. Carotid and bulbus intima media thickness were measured as early traits of atherosclerosis. Joint association of the modules, identified with weighted co-expression analysis, with early traits of the diseases was tested with multivariate analysis. Among the six modules significantly correlated with early traits of both the diseases, two had significant (adjusted p-values (p.adj) < 0.05) and another two had suggestively significant (p.adj < 0.25) joint association with the two diseases after adjusting for age, sex, body mass index, smoking habit, alcohol consumption, and physical activity. The three most significant member genes from the significant modules were NOSIP, GXYLT2, and TRIM63 (p.adj ≤ 0.18). Genes in the modules were enriched with biological processes that have separately been found to be involved in either bone metabolism or atherosclerosis. The gene modules and their most significant member genes identified in this study support the osteoporosis-atherosclerosis comorbidity hypothesis and can provide new joint biomarkers for both diseases and their dual prevention.

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Fitness costs and benefits of gene expression plasticity in rice under drought

10.1101/2021.03.16.435597 ◽

2021 ◽

Author(s):

Simon C Groen ◽

Elena Hamann ◽

Irina Calic ◽

Colleen Cochran ◽

Rachel Konshok ◽

...

Keyword(s):

Gene Expression ◽

Environmental Variability ◽

Housekeeping Genes ◽

Costs And Benefits ◽

Compensatory Evolution ◽

Architectural Features ◽

Genome Wide ◽

A Genome ◽

Gene Modules ◽

Genome Wide Gene Expression

Genome-wide gene expression changes in response to environmental variability have been widely documented, but we lack detailed and comprehensive understanding of the interplay between this form of phenotypic plasticity and natural selection. Selection on expression plasticity may be limited by environment-specific costs, and plasticity may in turn affect selection on baseline expression levels. Here, we address this fundamental issue by measuring selection on drought-induced plasticity of leaf transcripts in field-grown rice populations. Selection disfavored switching off housekeeping genes under drought. This stress-induced dysregulation did not constrain selection on baseline transcript levels, suggesting compensatory evolution may be possible. Selection rarely acted strongly on individual transcripts but worked polygenically on gradual (continuous) plasticity of co-expressed gene modules regulating photosynthesis via known drought-responsive transcription factors. Finally, selection was tied to inefficient gene architectural features and metabolic costs of expression. Our study provides a genome-wide view of costs and benefits of gene expression plasticity.

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Integrative Analysis of Genome-wide Gene Expression for Prostate Cancer Prognosis

10.21236/ada552228 ◽

2011 ◽

Author(s):

Jiyoung Ahn

Keyword(s):

Gene Expression ◽

Prostate Cancer ◽

Integrative Analysis ◽

Cancer Prognosis ◽

Genome Wide ◽

Genome Wide Gene Expression ◽

Prostate Cancer Prognosis

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Genome-wide gene expression changes in postpartum depression point towards an altered immune landscape

Translational Psychiatry ◽

10.1038/s41398-021-01270-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Divya Mehta ◽

Karen Grewen ◽

Brenda Pearson ◽

Shivangi Wani ◽

Leanne Wallace ◽

...

Keyword(s):

Gene Expression ◽

Depressive Symptoms ◽

Postpartum Depression ◽

Expression Profiles ◽

Depression Scale ◽

Well Being ◽

Health Concern ◽

Genome Wide ◽

A Genome ◽

Genome Wide Gene Expression

AbstractMaternal postpartum depression (PPD) is a significant public health concern due to the severe negative impact on maternal and child health and well-being. In this study, we aimed to identify genes associated with PPD. To do this, we investigated genome-wide gene expression profiles of pregnant women during their third trimester of pregnancy and tested the association of gene expression with perinatal depressive symptoms. A total of 137 women from a cohort from the University of North Carolina, USA were assessed. The main phenotypes analysed were Edinburgh Postnatal Depression Scale (EPDS) scores at 2 months postpartum and PPD (binary yes/no) based on an EPDS cutoff of 10. Illumina NextSeq500/550 transcriptomic sequencing from whole blood was analysed using the edgeR package. We identified 71 genes significantly associated with postpartum depression scores at 2 months, after correction for multiple testing at 5% FDR. These included several interesting candidates including TNFRSF17, previously reported to be significantly upregulated in women with PPD and MMP8, a matrix metalloproteinase gene, associated with depression in a genome-wide association study. Functional annotation of differentially expressed genes revealed an enrichment of immune response-related biological processes. Additional analysis of genes associated with changes in depressive symptoms from recruitment to 2 months postpartum identified 66 genes significant at an FDR of 5%. Of these genes, 33 genes were also associated with depressive symptoms at 2 months postpartum. Comparing the results with previous studies, we observed that 15.4% of genes associated with PPD in this study overlapped with 700 core maternal genes that showed significant gene expression changes across multiple brain regions (P = 7.9e-05) and 29–53% of the genes were also associated with estradiol changes in a pharmacological model of depression (P values range = 1.2e-4–2.1e-14). In conclusion, we identified novel genes and validated genes previously associated with oestrogen sensitivity in PPD. These results point towards the role of an altered immune transcriptomic landscape as a vulnerability factor for PPD.

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Arsenic hexoxide has differential effects on cell proliferation and genome-wide gene expression in human primary mammary epithelial and MCF7 cells

Scientific Reports ◽

10.1038/s41598-021-82551-3 ◽

2021 ◽

Vol 11 (1) ◽

Cited By ~ 1

Author(s):

Donguk Kim ◽

Na Yeon Park ◽

Keunsoo Kang ◽

Stuart K. Calderwood ◽

Dong-Hyung Cho ◽

...

Keyword(s):

Gene Expression ◽

Cell Cycle ◽

Cancer Cells ◽

Mammary Epithelial ◽

Mcf7 Cells ◽

Differential Effects ◽

Cycle Arrest ◽

Genome Wide ◽

Human Mammary Epithelial ◽

Genome Wide Gene Expression

AbstractArsenic is reportedly a biphasic inorganic compound for its toxicity and anticancer effects in humans. Recent studies have shown that certain arsenic compounds including arsenic hexoxide (AS4O6; hereafter, AS6) induce programmed cell death and cell cycle arrest in human cancer cells and murine cancer models. However, the mechanisms by which AS6 suppresses cancer cells are incompletely understood. In this study, we report the mechanisms of AS6 through transcriptome analyses. In particular, the cytotoxicity and global gene expression regulation by AS6 were compared in human normal and cancer breast epithelial cells. Using RNA-sequencing and bioinformatics analyses, differentially expressed genes in significantly affected biological pathways in these cell types were validated by real-time quantitative polymerase chain reaction and immunoblotting assays. Our data show markedly differential effects of AS6 on cytotoxicity and gene expression in human mammary epithelial normal cells (HUMEC) and Michigan Cancer Foundation 7 (MCF7), a human mammary epithelial cancer cell line. AS6 selectively arrests cell growth and induces cell death in MCF7 cells without affecting the growth of HUMEC in a dose-dependent manner. AS6 alters the transcription of a large number of genes in MCF7 cells, but much fewer genes in HUMEC. Importantly, we found that the cell proliferation, cell cycle, and DNA repair pathways are significantly suppressed whereas cellular stress response and apoptotic pathways increase in AS6-treated MCF7 cells. Together, we provide the first evidence of differential effects of AS6 on normal and cancerous breast epithelial cells, suggesting that AS6 at moderate concentrations induces cell cycle arrest and apoptosis through modulating genome-wide gene expression, leading to compromised DNA repair and increased genome instability selectively in human breast cancer cells.

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