scholarly journals RNA Sequencing Reveals Key Metabolic Pathways Are Modified by Short-Term Whole Egg Consumption

2021 ◽  
Vol 8 ◽  
Author(s):  
Amanda E. Bries ◽  
Joe L. Webb ◽  
Brooke Vogel ◽  
Claudia Carrillo ◽  
Timothy A. Day ◽  
...  
Keyword(s):  
Metabolic Pathways ◽  
Multiple Testing ◽  
Cholesterol Biosynthesis ◽  
Principal Component ◽  
Enrichment Analysis ◽  
Dietary Treatment ◽  
Glutathione Metabolism ◽  
Multiple Testing Correction ◽  
Egg Consumption ◽  
Whole Egg

Eggs are protein-rich, nutrient-dense, and contain bioactive ingredients that have been shown to modify gene expression and impact health. To understand the effects of egg consumption on tissue-specific mRNA and microRNA expression, we examined the role of whole egg consumption (20% protein, w/w) on differentially expressed genes (DEGs) between rat (n = 12) transcriptomes in the prefrontal cortex (PFC), liver, kidney, and visceral adipose tissue (VAT). Principal component analysis with hierarchical clustering was used to examine transcriptome profiles between dietary treatment groups. We performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis as well as genetic network and disease enrichment analysis to examine which metabolic pathways were the most predominantly altered in each tissue. Overall, our data demonstrates that whole egg consumption for 2 weeks modified the expression of 52 genes in the PFC, 22 genes in VAT, and two genes in the liver (adj p < 0.05). Additionally, 16 miRNAs were found to be differentially regulated in the PFC, VAT, and liver, but none survived multiple testing correction. The main pathways influenced by WE consumption were glutathione metabolism in VAT and cholesterol biosynthesis in the PFC. These data highlight key pathways that may be involved in diseases and are impacted by acute consumption of a diet containing whole eggs.

scholarly journals Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions

2018 ◽  
Author(s):  
David M. Howard ◽  
Mark J. Adams ◽  
Toni-Kim Clarke ◽  
Jonathan D. Hafferty ◽  
Jude Gibson ◽  
...  
Keyword(s):  
Multiple Testing ◽  
Drug Repositioning ◽  
Association Studies ◽  
Meta Analysis ◽  
Enrichment Analysis ◽  
Brain Regions ◽  
Genome Wide Association Studies ◽  
Multiple Testing Correction ◽  
Synaptic Structure ◽  
Genome Wide

AbstractMajor depression is a debilitating psychiatric illness that is typically associated with low mood, anhedonia and a range of comorbidities. Depression has a heritable component that has remained difficult to elucidate with current sample sizes due to the polygenic nature of the disorder. To maximise sample size, we meta-analysed data on 807,553 individuals (246,363 cases and 561,190 controls) from the three largest genome-wide association studies of depression. We identified 102 independent variants, 269 genes, and 15 gene-sets associated with depression, including both genes and gene-pathways associated with synaptic structure and neurotransmission. Further evidence of the importance of prefrontal brain regions in depression was provided by an enrichment analysis. In an independent replication sample of 1,306,354 individuals (414,055 cases and 892,299 controls), 87 of the 102 associated variants were significant following multiple testing correction. Based on the putative genes associated with depression this work also highlights several potential drug repositioning opportunities. These findings advance our understanding of the complex genetic architecture of depression and provide several future avenues for understanding aetiology and developing new treatment approaches.

Next-generation RNA sequencing reveals transcriptomic changes after brief exposure to preoperative nab-paclitaxel, bevacizumab, and trastuzumab.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10508-10508
Author(s):  
Vinay Varadan ◽  
Sitharthan Kamalakaran ◽  
Angel Janevski ◽  
Nila Banerjee ◽  
Kimberly Lezon-Geyda ◽  
...  
Keyword(s):  
Multiple Testing ◽  
Day Treatment ◽  
Transcriptional Response ◽  
Enrichment Analysis ◽  
Transcript Abundance ◽  
Differentially Expressed ◽  
Read Length ◽  
Breast Cancers ◽  
Rna Seq ◽  
Multiple Testing Correction

10508 Background: Identification of differentially expressed transcripts after brief exposure to preoperative therapy can help determine likely response markers. We quantify and compare differential gene and isoform expression using RNA-seq on patient samples with 10 day exposure to one dose of trastuzumab, bevacizumab or nab-paclitaxel. Methods: We sequenced transcriptomes of 23 pairs of core biopsy RNA from breast cancers pre/post 10 day exposure to therapy. Paired-end sequencing was done on the Illumina GAII platform using amplified total RNA with 74bp read length, yielding data on transcript abundance for a total of 22,160 genes and 34,449 transcripts. Differential expression of transcripts between pre/post samples was estimated assuming Poisson-distributed read-counts, followed by multiple testing correction and enrichment analysis of 185 KEGG pathways. Results: PAM50-based clustering showed individual samples cluster together, demonstrating that tumor subtypes do not change over the 10-day treatment (SABCS 2011). We identified genes that were significantly differentially expressed (p<0.05; FDR<0.1) in at least 60% of samples within each therapy arm: 780 genes in trastuzumab, 302 in bevacizumab, and 176 in nab-paclitaxel. Surprisingly, only THAP11 and TINF2 were common amongst them. THAP11 is involved in stem cell maintenance and TINF2 is important for regulation of telomere length. Immune system and metabolism-related pathways were commonly affected (p<0.05) across all arms. The bevacizumab arm showed significant down-regulation of angiogenesis-associated genes: ESM1 and VEGFR2 in > 80% of samples. The nab-paclitaxel arm exhibited changes in TGF-beta signaling, Nod-like receptor and Wnt signaling. The trastuzumab arm exhibited consistent alteration of ErbB2 and mTOR pathways, with SOX11 and TOP2B downregulated in every sample. Conclusions: This is the first study to compare gene expression with brief exposure across therapies using RNA-seq technology. The unique aspects of transcriptional response to each treatment underscore the need for specific markers of therapeutic response to nab-paclitaxel, bevacizumab and trastuzumab.

scholarly journals POEAS: Automated Plant Phenomic Analysis Using Plant Ontology

2014 ◽  
Vol 8 ◽  
pp. BBI.S19057 ◽  
Author(s):  
Khader Shameer ◽  
Mahantesha Bn Naika ◽  
Oommen K. Mathew ◽  
Ramanathan Sowdhamini
Keyword(s):  
Multiple Testing ◽  
Large Scale ◽  
Statistical Significance ◽  
Enrichment Analysis ◽  
Multiple Testing Correction ◽  
Background Population ◽  
Complementary Resource ◽  
Plant Ontology ◽  
Plant Genes ◽  
Cellular Components

Biological enrichment analysis using gene ontology (GO) provides a global overview of the functional role of genes or proteins identified from large-scale genomic or proteomic experiments. Phenomic enrichment analysis of gene lists can provide an important layer of information as well as cellular components, molecular functions, and biological processes associated with gene lists. Plant phenomic enrichment analysis will be useful for performing new experiments to better understand plant systems and for the interpretation of gene or proteins identified from high-throughput experiments. Plant ontology (PO) is a compendium of terms to define the diverse phenotypic characteristics of plant species, including plant anatomy, morphology, and development stages. Adoption of this highly useful ontology is limited, when compared to GO, because of the lack of user-friendly tools that enable the use of PO for statistical enrichment analysis. To address this challenge, we introduce Plant Ontology Enrichment Analysis Server (POEAS) in the public domain. POEAS uses a simple list of genes as input data and performs enrichment analysis using Ontologizer 2.0 to provide results in two levels, enrichment results and visualization utilities, to generate ontological graphs that are of publication quality. POEAS also offers interactive options to identify user-defined background population sets, various multiple-testing correction methods, different enrichment calculation methods, and resampling tests to improve statistical significance. The availability of such a tool to perform phenomic enrichment analyses using plant genes as a complementary resource will permit the adoption of PO-based phenomic analysis as part of analytical workflows. POEAS can be accessed using the URL http://caps.ncbs.res.in/poeas .

scholarly journals Genome-wide associations for udder and teat conformational risk factors for mastitis in Holstein cows

2019 ◽  
Author(s):  
Asha M. Miles ◽  
Christian Posbergh ◽  
Heather Jay Huson
Keyword(s):  
Cell Proliferation ◽  
Multiple Testing ◽  
Association Studies ◽  
Principal Component ◽  
Special Focus ◽  
Genome Wide Association Studies ◽  
Multiple Testing Correction ◽  
Genome Wide ◽  
Length Width ◽  
Mastitis Susceptibility

Abstract BACKGROUND The objective of our study was to conduct high-density genome-wide association studies of dairy cow udder and teat conformation with direct phenotyping. We identified and compared quantitative trait loci ( QTL ) for a novel composite mastitis risk trait and considered environmental impact of milking by comparing primiparous cows only. Cows (N = 471) were genotyped on the Illumina BovineHD 777K beadchip and scored for front and rear teat length, width, end shape, and placement, fore udder attachment, udder cleft, udder depth, rear udder height, and rear udder width. Principal component analysis was performed on fore udder attachment, rear teat end shape, rear teat width, and rear udder height, to create a single new phenotype describing mastitis susceptibility based on these high-risk traits.RESULTS Over all 14 traits of interest, a total of 56 genome-wide associations were performed and 28 significantly associated (Bonferroni multiple testing correction < 0.05) QTL were identified. The linkage disequilibrium ( LD ) block surrounding the associated QTL or a 1 Mb window in the absence of LD was interrogated for candidate genes, resulting in the identification of genes with functions related to both cell proliferation and immune signaling, including ZNF683, DHX9, CUX1, TNNT1 , and SPRY1 . We assessed a primiparous only subset of cows (n = 144) to account for the possibility that the genetic variance component of the phenotype is greater for cows who have had less exposure to the environment, and observed different associated QTL and inheritance patterns for udder depth in primiparous cows compared to the total cohort.CONCLUSION Special focus was given to the aforementioned mastitis risk traits, and candidate gene investigation revealed both immune function and cell proliferation related genes in the areas surrounding significantly associated QTL, suggesting that selecting for mastitis resistant cows based on these traits would be an effective method for increasing mastitis resiliency in a herd.

scholarly journals Metabolomic Links between Sugar-Sweetened Beverage Intake and Obesity

2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Bingjie Zhou ◽  
Reiko Ichikawa ◽  
Laurence D. Parnell ◽  
Sabrina E. Noel ◽  
Xiyuan Zhang ◽  
...  
Keyword(s):  
Metabolic Pathways ◽  
Multiple Testing ◽  
Enrichment Analysis ◽  
Health Study ◽  
Pathway Enrichment Analysis ◽  
Obesity Risk ◽  
Sugar Sweetened Beverage ◽  
Pathway Enrichment ◽  
Sweetened Beverage ◽  
Increased Risk

Background. Sugar-sweetened beverage (SSB) consumption is highly associated with obesity, but the metabolic mechanism underlying this correlation is not understood. Objective. Our objective was to examine metabolomic links between SSB intake and obesity to understand metabolic mechanisms. Design. We examined the association of plasma metabolomic profiles with SSB intake and obesity risk in 781 participants, aged 45–75 y, in the Boston Puerto Rican Health Study (BPRHS) using generalized linear models, controlling for potential confounding factors. Based on identified metabolites, we conducted pathway enrichment analysis to identify potential metabolic pathways that link SSB intake and obesity risk. Variants in genes encoding enzymes known to function in identified metabolic pathways were examined for their interactions with SSB intake on obesity. Results. SSB intake was correlated with BMI (β = 0.607, P=0.045). Among 526 measured metabolites, 86 showed a significant correlation with SSB intake and 148 with BMI (P≤0.05); 28 were correlated with both SSB intake and BMI (P≤0.05). Pathway enrichment analysis identified the phosphatidylcholine and lysophospholipid pathways as linking SSB intake to obesity, after correction for multiple testing. Furthermore, 8 of 10 genes functioning in these two pathways showed strong interaction with SSB intake on BMI. Our results further identified participants who may exhibit an increased risk of obesity when consuming SSB. Conclusions. We identified two key metabolic pathways that link SSB intake to obesity, revealing the potential of phosphatidylcholine and lysophospholipid to modulate how SSB intake can increase obesity risk. The interaction between genetic variants related to these pathways and SSB intake on obesity further supports the mechanism.

scholarly journals Epigenetic DNA methylation changes associated with headache chronification: A retrospective case-control study

Cephalalgia ◽  
2017 ◽  
Vol 38 (2) ◽  
pp. 312-322 ◽  
Author(s):  
Bendik S Winsvold ◽  
Priit Palta ◽  
Else Eising ◽  
Christian M Page ◽  
Arn MJM van den Maagdenberg ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Multiple Testing ◽  
Chronic Headache ◽  
Meta Analysis ◽  
Linear Regression Analysis ◽  
Enrichment Analysis ◽  
Functional Enrichment ◽  
Multiple Testing Correction ◽  
Retrospective Case ◽  
Cpg Sites

Background The biological mechanisms of headache chronification are poorly understood. We aimed to identify changes in DNA methylation associated with the transformation from episodic to chronic headache. Methods Participants were recruited from the population-based Norwegian HUNT Study. Thirty-six female headache patients who transformed from episodic to chronic headache between baseline and follow-up 11 years later were matched against 35 controls with episodic headache. DNA methylation was quantified at 485,000 CpG sites, and changes in methylation level at these sites were compared between cases and controls by linear regression analysis. Data were analyzed in two stages (Stages 1 and 2) and in a combined meta-analysis. Results None of the top 20 CpG sites identified in Stage 1 replicated in Stage 2 after multiple testing correction. In the combined meta-analysis the strongest associated CpG sites were related to SH2D5 and NPTX2, two brain-expressed genes involved in the regulation of synaptic plasticity. Functional enrichment analysis pointed to processes including calcium ion binding and estrogen receptor pathways. Conclusion In this first genome-wide study of DNA methylation in headache chronification several potentially implicated loci and processes were identified. The study exemplifies the use of prospectively collected population cohorts to search for epigenetic mechanisms of disease.

scholarly journals Genetic biomarkers in the VEGF pathway predicting response to anti-VEGF therapy in age-related macular degeneration

2019 ◽  
Vol 4 (1) ◽  
pp. e000273
Author(s):  
Irina Balikova ◽  
Laurence Postelmans ◽  
Brigitte Pasteels ◽  
Pascale Coquelet ◽  
Janet Catherine ◽  
...  
Keyword(s):  
Visual Acuity ◽  
Macular Degeneration ◽  
Treatment Response ◽  
Multiple Testing ◽  
Age Related Macular Degeneration ◽  
Patient Specific ◽  
Multiple Testing Correction ◽  
Anti Vegf ◽  
Age Related ◽  
Vegf Pathway

ObjectiveAge-related macular degeneration (ARMD) is a leading cause of visual impairment. Intravitreal injections of anti-vascular endothelial growth factor (VEGF) are the standard treatment for wet ARMD. There is however, variability in patient responses, suggesting patient-specific factors influencing drug efficacy. We tested whether single nucleotide polymorphisms (SNPs) in genes encoding VEGF pathway members contribute to therapy response.Methods and analysisA retrospective cohort of 281 European wet ARMD patients treated with anti-VEGF was genotyped for 138 tagging SNPs in the VEGF pathway. Per patient, we collected best corrected visual acuity at baseline, after three loading injections and at 12 months. We also registered the injection number and changes in retinal morphology after three loading injections (central foveal thickness (CFT), intraretinal cysts and serous neuroepithelium detachment). Changes in CFT after 3 months were our primary outcome measure. Association of SNPs to response was assessed by binomial logistic regression. Replication was attempted by associating visual acuity changes to genotypes in an independent Japanese cohort.ResultsAssociation with treatment response was detected for seven SNPs, including in FLT4 (rs55667289: OR=0.746, 95% CI 0.63 to 0.88, p=0.0005) and KDR (rs7691507: OR=1.056, 95% CI 1.02 to 1.10, p=0.005; and rs2305945: OR=0.963, 95% CI 0.93 to 1.00, p=0.0472). Only association with rs55667289 in FLT4 survived multiple testing correction. This SNP was unavailable for testing in the replication cohort. Of six SNPs tested for replication, one was significant although not after multiple testing correction.ConclusionIdentifying genetic variants that define treatment response can help to develop individualised therapeutic approaches for wet ARMD patients and may point towards new targets in non-responders.

Transcriptional identification of differentially expressed genes during the prepupal–pupal transition in the oriental armyworm, Mythimna separata (Walker) (Lepidoptera: Noctuidae)

2021 ◽  
pp. 1-14
Author(s):  
Peirong Li ◽  
Xinru Li ◽  
Wei Wang ◽  
Xiaoling Tan ◽  
Xiaoqi Wang ◽  
...  
Keyword(s):  
Differentially Expressed Genes ◽  
Metabolic Pathways ◽  
Developmental Stages ◽  
Kegg Pathway ◽  
Enrichment Analysis ◽  
Differentially Expressed ◽  
Mythimna Separata ◽  
Kegg Pathway Analysis ◽  
Oriental Armyworm ◽  
Lepidoptera Noctuidae

Abstract The oriental armyworm, Mythimna separata (Walker) is a serious pest of agriculture that does particular damage to Gramineae crops in Asia, Europe, and Oceania. Metamorphosis is a key developmental stage in insects, although the genes underlying the metamorphic transition in M. separata remain largely unknown. Here, we sequenced the transcriptomes of five stages; mature larvae (ML), wandering (W), and pupation (1, 5, and 10 days after pupation, designated P1, P5, and P10) to identify transition-associated genes. Four libraries were generated, with 22,884, 23,534, 26,643, and 33,238 differentially expressed genes (DEGs) for the ML-vs-W, W-vs-P1, P1-vs-P5, and P5-vs-P10, respectively. Gene ontology enrichment analysis of DEGs showed that genes regulating the biosynthesis of the membrane and integral components of the membrane, which includes the cuticular protein (CP), 20-hydroxyecdysone (20E), and juvenile hormone (JH) biosynthesis, were enriched. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that DEGs were enriched in the metabolic pathways. Of these DEGs, thirty CP, seventeen 20E, and seven JH genes were differentially expressed across the developmental stages. For transcriptome validation, ten CP, 20E, and JH-related genes were selected and verified by real-time PCR quantitative. Collectively, our results provided a basis for further studies of the molecular mechanism of metamorphosis in M. separata.

scholarly journals Cloning and overexpression of PeWRKY31 from Populus × euramericana enhances salt and biological tolerance in transgenic Nicotiana

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiaoyue Yu ◽  
Yu Pan ◽  
Yan Dong ◽  
Bin Lu ◽  
Chao Zhang ◽  
...  
Keyword(s):  
Salt Tolerance ◽  
Insect Resistance ◽  
Enrichment Analysis ◽  
Forest Tree ◽  
Mapk Signaling ◽  
Soil Salinization ◽  
Glutathione Metabolism ◽  
Plant Responses ◽  
Populus Euramericana ◽  
Biological Stress

Abstract Background As important forest tree species, biological stress and soil salinization are important factors that restrict the growth of Populus × euramericana. WRKYs are important transcription factors in plants that can regulate plant responses to biotic and abiotic stresses. In this study, PeWRKY31 was isolated from Populus × euramericana, and its bioinformation, salt resistance and insect resistance were analyzed. This study aims to provide guidance for producing salt-resistant and insect-resistant poplars. Results PeWRKY31 has a predicted open reading frame (ORF) of 1842 bp that encodes 613 amino acids. The predicted protein is the unstable, acidic, and hydrophilic protein with a molecular weight of 66.34 kDa, and it has numerous potential phosphorylation sites, chiefly on serines and threonines. PeWRKY31 is a zinc-finger C2H2 type-II WRKY TF that is closely related to WRKY TFs of Populus tomentosa, and localizes to the nucleus. A PeWRKY31 overexpression vector was constructed and transformed into Nicotiana tabacum L. Overexpression of PeWRKY31 improved the salt tolerance and insect resistance of the transgenic tobacco. Transcriptome sequencing and KEGG enrichment analysis showed the elevated expression of genes related to glutathione metabolism, plant hormone signal transduction, and MAPK signaling pathways, the functions of which were important in plant salt tolerance and insect resistance in the overexpressing tobacco line. Conclusions PeWRKY31 was isolated from Populus × euramericana. Overexpression of PeWRKY31 improved the resistance of transgenic plant to salt stress and pest stress. The study provides references for the generation of stress-resistant lines with potentially great economic benefit.

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