scholarly journals Genome Improvement and Core Gene Set Refinement of Fugacium kawagutii

2020 ◽  
Vol 8 (1) ◽  
pp. 102 ◽  
Author(s):  
Tangcheng Li ◽  
Liying Yu ◽  
Bo Song ◽  
Yue Song ◽  
Ling Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Annotation ◽  
Gene Prediction ◽  
Acid Synthesis ◽  
Core Gene ◽  
Chromosome Conformation ◽  
Gene Set ◽  
Kegg Pathways ◽  
Expression Studies ◽  
Gene Expression Studies

Cataloging an accurate functional gene set for the Symbiodiniaceae species is crucial for addressing biological questions of dinoflagellate symbiosis with corals and other invertebrates. To improve the gene models of Fugacium kawagutii, we conducted high-throughput chromosome conformation capture (Hi-C) for the genome and Illumina combined with PacBio sequencing for the transcriptome to achieve a new genome assembly and gene prediction. A 0.937-Gbp assembly of F. kawagutii were obtained, with a N50 > 13 Mbp and the longest scaffold of 121 Mbp capped with telomere motif at both ends. Gene annotation produced 45,192 protein-coding genes, among which, 11,984 are new compared to previous versions of the genome. The newly identified genes are mainly enriched in 38 KEGG pathways including N-Glycan biosynthesis, mRNA surveillance pathway, cell cycle, autophagy, mitophagy, and fatty acid synthesis, which are important for symbiosis, nutrition, and reproduction. The newly identified genes also included those encoding O-methyltransferase (O-MT), 3-dehydroquinate synthase, homologous-pairing protein 2-like (HOP2) and meiosis protein 2 (MEI2), which function in mycosporine-like amino acids (MAAs) biosynthesis and sexual reproduction, respectively. The improved version of the gene set (Fugka_Geneset _V3) raised transcriptomic read mapping rate from 33% to 54% and BUSCO match from 29% to 55%. Further differential gene expression analysis yielded a set of stably expressed genes under variable trace metal conditions, of which 115 with annotated functions have recently been found to be stably expressed under three other conditions, thus further developing the “core gene set” of F. kawagutii. This improved genome will prove useful for future Symbiodiniaceae transcriptomic, gene structure, and gene expression studies, and the refined “core gene set” will be a valuable resource from which to develop reference genes for gene expression studies.

Gene Expression Studies May Identify Lower Risk Myelodysplastic Syndrome Patients Likely to Respond to Therapy with Ezatiostat Hydrochloride (TLK199)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2779-2779
Author(s):  
Naomi Galili ◽  
Pablo Tamayo ◽  
Olga B Botvinnik ◽  
Jill P Mesirov ◽  
Jennifer Zikria ◽  
...  
Keyword(s):  
Gene Expression ◽  
Angiotensin Ii ◽  
Mononuclear Cells ◽  
Expression Data ◽  
Phase 2 ◽  
Glutathione S Transferase ◽  
Gene Set ◽  
Expression Studies ◽  
Phase 2 Study ◽  
Gene Expression Studies

Abstract Abstract 2779 Interpretation of gene expression studies in MDS have been especially challenging due to the heterogeneity of the cell lineages that comprise the malignant clone. In attempting to overcome these difficulties we have used a bedside-to-bench approach to define an expression signature that may identify patients likely to respond. Ezatiostat hydrochloride (TLK199) is an inhibitor of glutathione S-transferase, an enzyme that is over expressed in many cancers, and has been shown in vitro to stimulate growth and differentiation of hematopoietic progenitor cells and to induce apoptosis in leukemia cells. Based on multilineage responses in low-Int1 MDS patients in our phase 2 study of oral TLK199, a multi institutional phase 2 study was conducted in low-Int1 patients. Response was evaluated by International Working Group (IWG 2006) criteria. Pre-therapy bone marrow mononuclear cells of patients treated with TLK199 were analyzed for gene expression on the Illumina HT12v4 whole genome array with IRB approval. RNA isolated from the marrow mononuclear cells was available on 9 responders (R) and 21 non-responders (NR). Five R and 13 NR were randomly chosen to create a training set with the intent to later use the remaining samples for model testing. We identified the top 100 differentially expressed genes using a sensitive metric based on the normalized mutual information. We also performed single-sample Gene Set Enrichment Analysis to find the most salient differences in terms of pathways and biological processes between R/NR. Of special note are the 4 microRNA s differentially expressed between R/NR. Three miRNAs are under-expressed (miR-129, 802 and 548e) and one (miR-155) is over-expressed in R. Reduced expression of miR-129 has been reported in solid tumors when over-expressed has been shown to have anti-proliferative activity in cell lines. SOX4 is a target gene for miR129 and reduced expression of miR-129 results in concomitant up-regulation of SOX4 mRNA which can function as both an oncogene and a tumor suppressor gene depending on tumor lineage. Over-expression of SOX4 inhibited cytokine induced granulocyte maturation in the myeloid 32Dcl3 cell line suggesting a possible role in MDS. MiR-802 targets the receptor for angiotensin II and when expression is decreased there is increased angiotensin II activity. It has recently been shown that angiotensin is a pro-inflammatory mediator that participates in apoptosis, angiogenesis and promotes mitochondrial dysfunction, all characteristics of MDS. In addition, the transcription factor ZFHX3, a predicted target of miR-802, is a negative regulator of c-MYB which has been shown to be up-regulated in all subtypes of MDS. Similarly, c-MYB is a predicted target of miR-155, which is over-expressed in TLK199 responders. MiR-155 was shown to be over-expressed in marrow cells of a subset of human AML patients. Of particular note are the studies showing that sustained expression of miR-155 in mouse hematopoietic stem cells cause a myeloproliferative/myelodysplastic disorder. Subsequent pathway analysis of this expression data revealed that a JNK gene set as defined from the GEO dataset GDSS8081 was consistently under-expressed in responders and over-expressed in non-responders. TLK199 has been shown to induce JUN/JNK by binding to glutathione S-transferase, a key inhibitor of this pathway. The expression data confirms that patients whose pre-therapy marrow shows under-expression of the JNK gene set are precisely those who benefit from this drug therapy and those patients who already over-express these genes are unlikely to respond. This study highlights two important points: 1) Using a bedside-to-bench strategy yielded a signature that distinguished responders from non-responders 2) The signature identified genes and signaling pathways that shed light on both the biology of the disease and the mechanism of action of the drug. In conclusion, if these results are confirmed in the test set, we will use the signature in a future prospective study to preselect MDS patients for therapy with this promising drug. Disclosures: Brown: Telik, Inc.: Employment, Equity Ownership.

scholarly journals Genes identified in rodent studies of alcohol intake are enriched for heritability of human substance use

2021 ◽  
Author(s):  
Spencer B. Huggett ◽  
Emma C. Johnson ◽  
Alexander S. Hatoum ◽  
Dongbing Lai ◽  
Jason A. Bubier ◽  
...  
Keyword(s):  
Gene Expression ◽  
Smoking Cessation ◽  
Substance Use ◽  
Alcohol Use ◽  
Gene Set ◽  
Problematic Alcohol ◽  
Gene Sets ◽  
Expression Studies ◽  
Gene Expression Studies ◽  
Problematic Alcohol Use

ABSTRACTBackgroundRodent paradigms and human genome-wide association studies (GWASs) on drug use have the potential to provide biological insight into the pathophysiology of addiction.MethodsUsing GeneWeaver, we created rodent alcohol and nicotine gene-sets derived from 19 gene expression studies on alcohol and nicotine outcomes. We partitioned the SNP-heritability of these gene-sets using four large human GWASs: 1) alcoholic drinks per week, 2) problematic alcohol use, 3) cigarettes per day and 4) smoking cessation. We benchmarked our findings with curated human alcoholism and nicotine addiction gene-sets and performed specificity analyses using other rodent gene-sets (e.g., locomotor behavior) and other human GWASs (e.g., height).ResultsThe rodent alcohol gene-set was enriched for heritability of drinks per week, cigarettes per day, and smoking cessation, but not problematic alcohol use. However, the rodent nicotine gene-set was not significantly associated with any of these traits. Both rodent gene-sets showed enrichment for several non-substance use GWASs, and the extent of this relationship tended to increase as a function of trait heritability. In general, larger gene-sets demonstrated more significant enrichment. Finally, when evaluating human traits with similar heritabilities, both rodent gene-sets showed greater enrichment for substance use traits.ConclusionOur results suggest that rodent gene expression studies can help to identify genes that capture heritability of substance use traits in humans, yet the specificity to human substance use was less than expected due to various factors such as the genetic architecture of a trait. We outline various limitations, interpretations and considerations for future research.

scholarly journals Transcriptomics and network analysis highlight potential pathways in the pathogenesis of pterygium

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Juliana Albano de Guimarães ◽  
Bidossessi Wilfried Hounpke ◽  
Bruna Duarte ◽  
Ana Luiza Mylla Boso ◽  
Marina Gonçalves Monteiro Viturino ◽  
...  
Keyword(s):  
Gene Expression ◽  
Extracellular Matrix ◽  
Regulatory Network ◽  
Meta Analysis ◽  
Gene Set Analysis ◽  
Expression Data ◽  
Gene Set ◽  
Expression Studies ◽  
Gene Expression Studies ◽  
Brazilian Cohort

AbstractPterygium is a common ocular surface condition frequently associated with irritative symptoms. The precise identity of its critical triggers as well as the hierarchical relationship between all the elements involved in the pathogenesis of this disease are not yet elucidated. Meta-analysis of gene expression studies represents a novel strategy capable of identifying key pathogenic mediators and therapeutic targets in complex diseases. Samples from nine patients were collected during surgery after photo documentation and clinical characterization of pterygia. Gene expression experiments were performed using Human Clariom D Assay gene chip. Differential gene expression analysis between active and atrophic pterygia was performed using limma package after adjusting variables by age. In addition, a meta-analysis was performed including recent gene expression studies available at the Gene Expression Omnibus public repository. Two databases including samples from adults with pterygium and controls fulfilled our inclusion criteria. Meta-analysis was performed using the Rank Production algorithm of the RankProd package. Gene set analysis was performed using ClueGO and the transcription factor regulatory network prediction was performed using appropriate bioinformatics tools. Finally, miRNA-mRNA regulatory network was reconstructed using up-regulated genes identified in the gene set analysis from the meta-analysis and their interacting miRNAs from the Brazilian cohort expression data. The meta-analysis identified 154 up-regulated and 58 down-regulated genes. A gene set analysis with the top up-regulated genes evidenced an overrepresentation of pathways associated with remodeling of extracellular matrix. Other pathways represented in the network included formation of cornified envelopes and unsaturated fatty acid metabolic processes. The miRNA-mRNA target prediction network, also reconstructed based on the set of up-regulated genes presented in the gene ontology and biological pathways network, showed that 17 target genes were negatively correlated with their interacting miRNAs from the Brazilian cohort expression data. Once again, the main identified cluster involved extracellular matrix remodeling mechanisms, while the second cluster involved formation of cornified envelope, establishment of skin barrier and unsaturated fatty acid metabolic process. Differential expression comparing active pterygium with atrophic pterygium using data generated from the Brazilian cohort identified differentially expressed genes between the two forms of presentation of this condition. Our results reveal differentially expressed genes not only in pterygium, but also in active pterygium when compared to the atrophic ones. New insights in relation to pterygium’s pathophysiology are suggested.

scholarly journals Statistical Approach of Gene Set Analysis with Quantitative Trait Loci for Crop Gene Expression Studies

Entropy ◽  
2021 ◽  
Vol 23 (8) ◽  
pp. 945
Author(s):  
Samarendra Das ◽  
Shesh N. Rai
Keyword(s):  
Gene Expression ◽  
Gene Expression Data ◽  
Statistical Approach ◽  
Gene Set Analysis ◽  
Expression Data ◽  
Expression Study ◽  
Gene Set ◽  
Gene Sets ◽  
Expression Studies ◽  
Gene Expression Studies

Genome-wide expression study is a powerful genomic technology to quantify expression dynamics of genes in a genome. In gene expression study, gene set analysis has become the first choice to gain insights into the underlying biology of diseases or stresses in plants. It also reduces the complexity of statistical analysis and enhances the explanatory power of the obtained results from the primary downstream differential expression analysis. The gene set analysis approaches are well developed in microarrays and RNA-seq gene expression data analysis. These approaches mainly focus on analyzing the gene sets with gene ontology or pathway annotation data. However, in plant biology, such methods may not establish any formal relationship between the genotypes and the phenotypes, as most of the traits are quantitative and controlled by polygenes. The existing Quantitative Trait Loci (QTL)-based gene set analysis approaches only focus on the over-representation analysis of the selected genes while ignoring their associated gene scores. Therefore, we developed an innovative statistical approach, GSQSeq, to analyze the gene sets with trait enriched QTL data. This approach considers the associated differential expression scores of genes while analyzing the gene sets. The performance of the developed method was tested on five different crop gene expression datasets obtained from real crop gene expression studies. Our analytical results indicated that the trait-specific analysis of gene sets was more robust and successful through the proposed approach than existing techniques. Further, the developed method provides a valuable platform for integrating the gene expression data with QTL data.

scholarly journals Assessment of common housekeeping genes as reference for gene expression studies using RT-qPCR in mouse choroid plexus

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kim Hoa Ho ◽  
Annarita Patrizi
Keyword(s):  
Gene Expression ◽  
Choroid Plexus ◽  
Sensory Deprivation ◽  
Housekeeping Genes ◽  
Housekeeping Gene ◽  
Experimental Conditions ◽  
Brain Repair ◽  
Expression Studies ◽  
Testing Algorithms ◽  
Gene Expression Studies

AbstractChoroid plexus (ChP), a vascularized secretory epithelium located in all brain ventricles, plays critical roles in development, homeostasis and brain repair. Reverse transcription quantitative real-time PCR (RT-qPCR) is a popular and useful technique for measuring gene expression changes and also widely used in ChP studies. However, the reliability of RT-qPCR data is strongly dependent on the choice of reference genes, which are supposed to be stable across all samples. In this study, we validated the expression of 12 well established housekeeping genes in ChP in 2 independent experimental paradigms by using popular stability testing algorithms: BestKeeper, DeltaCq, geNorm and NormFinder. Rer1 and Rpl13a were identified as the most stable genes throughout mouse ChP development, while Hprt1 and Rpl27 were the most stable genes across conditions in a mouse sensory deprivation experiment. In addition, Rpl13a, Rpl27 and Tbp were mutually among the top five most stable genes in both experiments. Normalisation of Ttr and Otx2 expression levels using different housekeeping gene combinations demonstrated the profound effect of reference gene choice on target gene expression. Our study emphasized the importance of validating and selecting stable housekeeping genes under specific experimental conditions.

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