scholarly journals Genomic Modules and Intramodular Network Convergency of Susceptibility and Resilience in Multimodeled Stress in Male Mice

2021 ◽  
Author(s):  
Jordan Marrocco ◽  
Salvatore G Caradonna ◽  
Tie-Yuan Zhang ◽  
Nicholas O'Toole ◽  
Mo-Jun Shen ◽  
...  
Keyword(s):  
Construct Validity ◽  
Gene Networks ◽  
Anxiety And Depression ◽  
Rna Seq ◽  
Data Set ◽  
Genomic Signatures ◽  
Medical Standards ◽  
Gene Coding ◽  
Chronic Social Defeat Stress ◽  
Response To Stress

The multifactorial etiology of stress-related disorders is a challenge in developing synchronized medical standards for treatment and diagnosis. It is largely unknown whether there exists molecular convergence in preclinical models of stress generated using disparate construct validity. Using RNA-sequencing (RNA-seq), we investigated the genomic signatures in the ventral hippocampus, which mostly regulates affective behavior, in mouse models that recapitulate the hallmarks of anxiety and depression. Chronic oral corticosterone (CORT), a model that causes a blunted endocrine response to stress, induced anxiety- and depression-like behavior in wildtype mice and mice heterozygous for the gene coding for brain-derived neurotrophic factor (BDNF) Val66Met, a variant associated with genetic susceptibility to stress. In a separate set of mice, chronic social defeat stress led to a susceptible or a resilient population, whose proportion was dependent on housing conditions, standard housing or enriched environment. A rank-rank-hypergeometric (RRHO) analysis of the RNA-seq data set across models demonstrated that in mice treated with CORT and susceptible mice raised in standard housing differentially expressed genes (DEGs) converged toward gene networks involved in similar biological functions. Weighted gene co-expression analysis generated 54 unique modules of interconnected gene hubs, two of which included a combination of all experimental groups and were significantly enriched in DEGs, whose function was consistent with that predicted in the RRHO GO analysis. This multimodel approach showed transcriptional synchrony between models of stress with hormonal, environmental or genetic construct validity shedding light on common genomic drivers that embody the multifaceted nature of stress-related disorders.

scholarly journals Genomic modules and intramodular network concordance in susceptible and resilient male mice across models of stress

2021 ◽  
Author(s):  
Salvatore G. Caradonna ◽  
Tie-Yuan Zhang ◽  
Nicholas O’Toole ◽  
Mo-Jun Shen ◽  
Huzefa Khalil ◽  
...  
Keyword(s):  
Gene Networks ◽  
Anxiety And Depression ◽  
Stress Coping ◽  
Housing Conditions ◽  
Male Mice ◽  
Wild Type ◽  
Genomic Signatures ◽  
Gene Coding ◽  
Chronic Social Defeat Stress ◽  
Wild Type Male

AbstractThe multifactorial etiology of stress-related disorders necessitates a constant interrogation of the molecular convergences in preclinical models of stress that use disparate paradigms as stressors spanning from environmental challenges to genetic predisposition to hormonal signaling. Using RNA-sequencing, we investigated the genomic signatures in the ventral hippocampus common to mouse models of stress. Chronic oral corticosterone (CORT) induced increased anxiety- and depression-like behavior in wild-type male mice and male mice heterozygous for the gene coding for brain-derived neurotrophic factor Val66Met, a variant associated with genetic susceptibility to stress. In a separate set of male mice, chronic social defeat stress (CSDS) led to a susceptible or a resilient population, whose proportion was dependent on housing conditions, namely standard housing or enriched environment. Rank-rank-hypergeometric overlap (RRHO), a threshold-free approach that ranks genes by their p value and effect size direction, was used to identify genes from a continuous gradient of significancy that were concordant across groups. In mice treated with CORT and in standard-housed susceptible mice, differentially expressed genes (DEGs) were concordant for gene networks involved in neurotransmission, cytoskeleton function, and vascularization. Weighted gene co-expression analysis generated 54 gene hub modules and revealed two modules in which both CORT and CSDS-induced enrichment in DEGs, whose function was concordant with the RRHO predictions, and correlated with behavioral resilience or susceptibility. These data showed transcriptional concordance across models in which the stress coping depends upon hormonal, environmental, or genetic factors revealing common genomic drivers that embody the multifaceted nature of stress-related disorders.

scholarly journals Coordinated analysis of exon and intron data reveals novel differential gene expression changes

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Hamid R. Eghbalnia ◽  
William W. Wilfinger ◽  
Karol Mackey ◽  
Piotr Chomczynski
Keyword(s):  
Gene Networks ◽  
Expression Data ◽  
Rna Seq ◽  
Data Set ◽  
Exon Expression ◽  
Regulatory Processes ◽  
Pathway Gene ◽  
Immune Pathway ◽  
Archived Data

Abstract RNA-Seq expression analysis currently relies primarily upon exon expression data. The recognized role of introns during translation, and the presence of substantial RNA-Seq counts attributable to introns, provide the rationale for the simultaneous consideration of both exon and intron data. We describe here a method for the coordinated analysis of exon and intron data by investigating their relationship within individual genes and across samples, while taking into account changes in both variability and expression level. This coordinated analysis of exon and intron data offers strong evidence for significant differences that distinguish the profiles of the exon-only expression data from the combined exon and intron data. One advantage of our proposed method, called matched change characterization for exons and introns (MEI), is its straightforward applicability to existing archived data using small modifications to standard RNA-Seq pipelines. Using MEI, we demonstrate that when data are examined for changes in variability across control and case conditions, novel differential changes can be detected. Notably, when MEI criteria were employed in the analysis of an archived data set involving polyarthritic subjects, the number of differentially expressed genes was expanded by sevenfold. More importantly, the observed changes in exon and intron variability with statistically significant false discovery rates could be traced to specific immune pathway gene networks. The application of MEI analysis provides a strategy for incorporating the significance of exon and intron variability and further developing the role of using both exons and intron sequencing counts in studies of gene regulatory processes.

scholarly journals A mutation in LacDWARF1 results in a GA-deficient dwarf phenotype in sponge gourd (Luffa acutangula)

2021 ◽  
Author(s):  
Gangjun Zhao ◽  
Caixia Luo ◽  
Jianning Luo ◽  
Junxing Li ◽  
Hao Gong ◽  
...  
Keyword(s):  
Gene Annotation ◽  
Recessive Gene ◽  
Genomic Region ◽  
Dwarf Mutant ◽  
Rna Seq ◽  
Dwarf Phenotype ◽  
Sponge Gourd ◽  
Response To Stress ◽  
Luffa Acutangula ◽  
Generation Sequencing

Abstract Key message A dwarfism gene LacDWARF1 was mapped by combined BSA-Seq and comparative genomics analyses to a 65.4 kb physical genomic region on chromosome 05. Abstract Dwarf architecture is one of the most important traits utilized in Cucurbitaceae breeding because it saves labor and increases the harvest index. To our knowledge, there has been no prior research about dwarfism in the sponge gourd. This study reports the first dwarf mutant WJ209 with a decrease in cell size and internodes. A genetic analysis revealed that the mutant phenotype was controlled by a single recessive gene, which is designated Lacdwarf1 (Lacd1). Combined with bulked segregate analysis and next-generation sequencing, we quickly mapped a 65.4 kb region on chromosome 5 using F2 segregation population with InDel and SNP polymorphism markers. Gene annotation revealed that Lac05g019500 encodes a gibberellin 3β-hydroxylase (GA3ox) that functions as the most likely candidate gene for Lacd1. DNA sequence analysis showed that there is an approximately 4 kb insertion in the first intron of Lac05g019500 in WJ209. Lac05g019500 is transcribed incorrectly in the dwarf mutant owing to the presence of the insertion. Moreover, the bioactive GAs decreased significantly in WJ209, and the dwarf phenotype could be restored by exogenous GA3 treatment, indicating that WJ209 is a GA-deficient mutant. All these results support the conclusion that Lac05g019500 is the Lacd1 gene. In addition, RNA-Seq revealed that many genes, including those related to plant hormones, cellular process, cell wall, membrane and response to stress, were significantly altered in WJ209 compared with the wild type. This study will aid in the use of molecular marker-assisted breeding in the dwarf sponge gourd.

scholarly journals OsMYB80 Regulates Anther Development and Pollen Fertility by Targeting Multiple Biological Pathways

2020 ◽  
Vol 61 (5) ◽  
pp. 988-1004 ◽  
Author(s):  
Xiaoying Pan ◽  
Wei Yan ◽  
Zhenyi Chang ◽  
Yingchao Xu ◽  
Ming Luo ◽  
...  
Keyword(s):  
Pollen Development ◽  
Male Fertility ◽  
Gene Networks ◽  
Affinity Purification ◽  
Anther Development ◽  
Rna Seq ◽  
Male Sterile ◽  
New Information ◽  
Gel Shift Assay

Abstract Pollen development is critical to the reproductive success of flowering plants, but how it is regulated is not well understood. Here, we isolated two allelic male-sterile mutants of OsMYB80 and investigated how OsMYB80 regulates male fertility in rice. OsMYB80 was barely expressed in tissues other than anthers, where it initiated the expression during meiosis, reached the peak at the tetrad-releasing stage and then quickly declined afterward. The osmyb80 mutants exhibited premature tapetum cell death, lack of Ubisch bodies, no exine and microspore degeneration. To understand how OsMYB80 regulates anther development, RNA-seq analysis was conducted to identify genes differentially regulated by OsMYB80 in rice anthers. In addition, DNA affinity purification sequencing (DAP-seq) analysis was performed to identify DNA fragments interacting with OsMYB80 in vitro. Overlap of the genes identified by RNA-seq and DAP-seq revealed 188 genes that were differentially regulated by OsMYB80 and also carried an OsMYB80-interacting DNA element in the promoter. Ten of these promoter elements were randomly selected for gel shift assay and yeast one-hybrid assay, and all showed OsMYB80 binding. The 10 promoters also showed OsMYB80-dependent induction when co-expressed in rice protoplast. Functional annotation of the 188 genes suggested that OsMYB80 regulates male fertility by directly targeting multiple biological processes. The identification of these genes significantly enriched the gene networks governing anther development and provided much new information for the understanding of pollen development and male fertility.

P.1.003 Gene networks and blood biomarkers of methamphetamine-associated psychosis: a preliminary integrative RNA-Seq report

2016 ◽  
Vol 26 ◽  
pp. S4-S5
Author(s):  
M.S. Breen ◽  
A. Uhlmann ◽  
C. Nday ◽  
S. Glatt ◽  
A. Metsalpu ◽  
...  
Keyword(s):  
Gene Networks ◽  
Rna Seq ◽  
Blood Biomarkers

Religious and Sexual Identities: An Intersectional, Longitudinal Examination of Change in Therapy

2017 ◽  
Vol 45 (3) ◽  
pp. 387-413 ◽  
Author(s):  
G. Tyler Lefevor ◽  
Rebecca A. Janis ◽  
So Yeon Park
Keyword(s):  
Mental Health ◽  
Hierarchical Linear Modeling ◽  
Anxiety Symptoms ◽  
Anxiety And Depression ◽  
Linear Modeling ◽  
Data Set ◽  
Sexual Identities ◽  
Rates Of Change ◽  
Lower Baseline ◽  
Longitudinal Examination

The current study employs an intersectional framework to understand how well counselors are meeting the needs of lesbian, gay, bisexual, queer, questioning (LGBQQ) and religious clients by examining clients’ initial anxiety and depression levels and changes in these symptoms through psychotherapy. Data from 12,825 participants from the Center for Collegiate Mental Health 2012–2014 data set were analyzed. Results from hierarchical linear modeling indicate lower baseline anxiety and depression among religious clients and faster rates of change of anxiety symptoms among nonreligious clients. LGBQQ clients presented with higher initial anxiety and depression, but there were no differences in rates of change of anxiety and depression between heterosexual and LGBQQ clients. Significant but minimal interaction effects between religious and sexual identities were found, indicating a need for further research. Counselors are encouraged to be mindful of these disparities in therapy.

scholarly journals Phosphate transporter genes: genome-wide identification and characterization in Camelina sativa

2021 ◽  
Author(s):  
Soosan Hasanzadeh ◽  
Sahar Faraji ◽  
Abdullah ◽  
Parviz Heidari
Keyword(s):  
Phosphate Transporter ◽  
Rna Seq ◽  
Specific Expression ◽  
Cis Acting ◽  
Genome Wide ◽  
Sodium Dependent ◽  
Intron Number ◽  
Response To Stress ◽  
Growth Energy ◽  
Root Tissues

Phosphorus is known as a key element associated with growth, energy, and cell signaling. In plants, phosphate transporters (PHTs) are responsible for moving and distributing phosphorus in cells and organs. PHT genes have been genome-wide identified and characterized in various plant species, however, these genes have not been widely identified based on available genomic data in Camellia sativa, which is an important oil seed plant. In the present study, we found 66 PHT genes involved in phosphate transporter/translocate in C. sativa. The recognized genes belonged to PHTs1, PHTs2, PHTs4, PHOs1, PHO1 homologs, glycerol-3-PHTs, sodium dependent PHTs, inorganic PHTs, xylulose 5-PHTs, glucose-6-phosphate translocators, and phosphoenolpyruvate translocators. Our finding revealed that PHT proteins are divers based on their physicochemical properties such as Isoelectric point (pI), molecular weight, GRAVY value, and exon-intron number(s). Besides, the expression profile of PHT genes in C. sativa based on RNA-seq data indicate that PHTs are involved in response to abiotic stresses such as cold, drought, salt, and cadmium. The tissue specific expression high expression of PHO1 genes in root tissues of C. sativa. In additions, four PHTs, including a PHT4;5 gene, a sodium dependent PHT gene, and two PHO1 homolog 3 genes were found with an upregulation in response to aforementioned studied stresses. In the current study, we found that PHO1 proteins and their homologs have high potential to post-translation modifications such as N-glycosylation and phosphorylation. Besides, different cis-acting elements associated with response to stress and phytohormone were found in the promoter region of PHT genes. Overall, our results show that PHT genes play various functions in C. Sativa and regulate Camellia responses to external and intracellular stimuli. The results can be used in future studies related to the functional genomics of C. sativa.

scholarly journals Mixture models reveal multiple positional bias types in RNA-Seq data and lead to accurate transcript concentration estimates

2014 ◽  
Author(s):  
Andreas Tuerk ◽  
Gregor Wiktorin ◽  
Serhat Güler
Keyword(s):  
Probability Distributions ◽  
False Positive Rate ◽  
Synthetic Data ◽  
True Positive Rate ◽  
Rna Seq ◽  
Microarray Quality Control ◽  
Data Set ◽  
Rna Transcripts ◽  
Positive Rate ◽  
Fragment Distribution

Quantification of RNA transcripts with RNA-Seq is inaccurate due to positional fragment bias, which is not represented appropriately by current statistical models of RNA-Seq data. This article introduces the Mix2(rd. "mixquare") model, which uses a mixture of probability distributions to model the transcript specific positional fragment bias. The parameters of the Mix2model can be efficiently trained with the Expectation Maximization (EM) algorithm resulting in simultaneous estimates of the transcript abundances and transcript specific positional biases. Experiments are conducted on synthetic data and the Universal Human Reference (UHR) and Brain (HBR) sample from the Microarray quality control (MAQC) data set. Comparing the correlation between qPCR and FPKM values to state-of-the-art methods Cufflinks and PennSeq we obtain an increase in R2value from 0.44 to 0.6 and from 0.34 to 0.54. In the detection of differential expression between UHR and HBR the true positive rate increases from 0.44 to 0.71 at a false positive rate of 0.1. Finally, the Mix2model is used to investigate biases present in the MAQC data. This reveals 5 dominant biases which deviate from the common assumption of a uniform fragment distribution. The Mix2software is available at http://www.lexogen.com/fileadmin/uploads/bioinfo/mix2model.tgz.

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