scholarly journals Identification of Clinical Relevant Molecular Subtypes of Pheochromocytoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Umair Ali Khan Saddozai ◽  
Fengling Wang ◽  
Muhammad Usman Akbar ◽  
Lu Zhang ◽  
Yang An ◽  
...  
Keyword(s):  
Gene Expression ◽  
Targeted Therapies ◽  
Expression Patterns ◽  
Smooth Muscle Contraction ◽  
High Rate ◽  
Receptor Interaction ◽  
Data Sets ◽  
Effective Treatment Option ◽  
Using Data ◽  
Underlying Mechanisms

Pheochromocytoma (PCC) is a rare neuroendocrine tumor of the adrenal gland with a high rate of mortality if diagnosed at a late stage. Common symptoms of pheochromocytoma include headache, anxiety, palpitation, and diaphoresis. Different treatments are under observation for PCC but there is still no effective treatment option. Recently, the gene expression profiling of various tumors has provided new subtype-specific options for targeted therapies. In this study, using data sets from TCGA and the GSE19422 cohorts, we identified two distinct PCC subtypes with distinct gene expression patterns. Genes enriched in Subtype I PCCs were involved in the dopaminergic synapse, nicotine addiction, and long-term depression pathways, while genes enriched in subtype II PCCs were involved in protein digestion and absorption, vascular smooth muscle contraction, and ECM receptor interaction pathways. We further identified subtype specific genes such as ALK, IGF1R, RET, and RSPO2 for subtype I and EGFR, ESR1, and SMO for subtype II, the overexpression of which led to cell invasion and tumorigenesis. These genes identified in the present research may serve as potential subtype-specific therapeutic targets to understand the underlying mechanisms of tumorigenesis. Our findings may further guide towards the development of targeted therapies and potential molecular biomarkers against PCC.

A Global Vista of the Epigenomic State of the Mouse Submandibular Gland

2021 ◽  
pp. 002203452110120
Author(s):  
C. Gluck ◽  
S. Min ◽  
A. Oyelakin ◽  
M. Che ◽  
E. Horeth ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcriptional Control ◽  
Expression Patterns ◽  
Global Gene Expression ◽  
Regulatory Elements ◽  
Specific Gene ◽  
Submandibular Salivary Gland ◽  
Data Sets ◽  
Control Mechanisms ◽  
Chromatin Immunoprecipitation Sequencing

The parotid, submandibular, and sublingual glands represent a trio of oral secretory glands whose primary function is to produce saliva, facilitate digestion of food, provide protection against microbes, and maintain oral health. While recent studies have begun to shed light on the global gene expression patterns and profiles of salivary glands, particularly those of mice, relatively little is known about the location and identity of transcriptional control elements. Here we have established the epigenomic landscape of the mouse submandibular salivary gland (SMG) by performing chromatin immunoprecipitation sequencing experiments for 4 key histone marks. Our analysis of the comprehensive SMG data sets and comparisons with those from other adult organs have identified critical enhancers and super-enhancers of the mouse SMG. By further integrating these findings with complementary RNA-sequencing based gene expression data, we have unearthed a number of molecular regulators such as members of the Fox family of transcription factors that are enriched and likely to be functionally relevant for SMG biology. Overall, our studies provide a powerful atlas of cis-regulatory elements that can be leveraged for better understanding the transcriptional control mechanisms of the mouse SMG, discovery of novel genetic switches, and modulating tissue-specific gene expression in a targeted fashion.

scholarly journals Molecular Characteristics of Streptococcus pyogenes Isolated From Chinese Children With Different Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Dingle Yu ◽  
Yunmei Liang ◽  
Qinghua Lu ◽  
Qing Meng ◽  
Wenjian Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Antibiotic Resistance ◽  
Streptococcus Pyogenes ◽  
Wide Spectrum ◽  
Expression Patterns ◽  
Virulence Gene ◽  
High Rate ◽  
Molecular Characteristics ◽  
Virulence Gene Expression ◽  
Obstructive Sleep

Streptococcus pyogenes is a bacterial pathogen that causes a wide spectrum of clinical diseases exclusively in humans. The distribution of emm type, antibiotic resistance and virulence gene expression for S. pyogenes varies temporally and geographically, resulting in distinct disease spectra. In this study, we analyzed antibiotic resistance and resistance gene expression patterns among S. pyogenes isolates from pediatric patients in China and investigated the relationship between virulence gene expression, emm type, and disease categories. Forty-two representative emm1.0 and emm12.0 strains (n = 20 and n = 22, respectively) isolated from patients with scarlet fever or obstructive sleep apnea-hypopnea syndrome were subjected to whole-genome sequencing and phylogenetic analysis. These strains were further analyzed for susceptibility to vancomycin. We found a high rate and degree of resistance to macrolides and tetracycline in these strains, which mainly expressed ermB and tetM. The disease category correlated with emm type but not superantigens. The distribution of vanuG and virulence genes were associated with emm type. Previously reported important prophages, such as φHKU16.vir, φHKU488.vir, Φ5005.1, Φ5005.2, and Φ5005.3 encoding streptococcal toxin, and integrative conjugative elements (ICEs) such as ICE-emm12 and ICE-HKU397 encoding macrolide and tetracycline resistance were found present amongst emm1 or emm12 clones from Shenzhen, China.

scholarly journals Transcriptome Dynamics Reveal Stage-Specific and Melatonin-Triggered Gene Expression Patterns During The Cashmere Growth Cycle in Capra Hircus

2021 ◽  
Author(s):  
Chun Li ◽  
Cong Feng ◽  
Guangyuan Ma ◽  
Shaoyin Fu ◽  
Ming Chen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Signaling Pathways ◽  
Expression Patterns ◽  
Growth Cycle ◽  
Hair Follicles ◽  
Receptor Interaction ◽  
Morphological Evidence ◽  
Gene Expression Patterns ◽  
Growth Stages ◽  
Nf Kappa B

Abstract Background Cashmere goat is famous for its high-quality fibers. The growth of cashmere in secondary hair follicles exhibits a seasonal pattern arising from circannual changes in the natural photoperiod. Although several studies have compared and analyzed the differences in gene expression between different cashmere growth stages, the selection of samples in these studies relies on research experience or morphological evidence. Distinguishing cashmere growth cycle according to gene expression patterns may help to explore the regulation mechanisms related to cashmere growth and the effect of melatonin from a molecular level more accurately. Results In this study, we applied RNA-sequencing to the hair follicles of three normal and three melatonin-treated Inner Mongolian cashmere goats sampled every month during a whole cashmere growth cycle. A total of 3559 and 988 genes were subjected as seasonal changing genes (SCGs) in the control and treated groups, respectively. The SCGs in the normal group are divided into three clusters, and their specific expression patterns help to group the cashmere growth cycle into anagen, catagen and telogen stages. Some canonical pathways such as Wnt, TGF-beta and Hippo signaling pathways are detected as promoting the cashmere growth, while Cell adhesion molecules (CAMs), Cytokine-cytokine receptor interaction, Jak-STAT, Fc epsilon RI, NOD-like receptor, Rap1, PI3K-Akt, cAMP, NF-kappa B and many immune-related pathways are detected in the catagen and telogen stages. The PI3K-Akt signaling, ECM-receptor interaction and Focal adhesion are found in the transition stage between telogen to anagen, which may serve as candidate biomarkers for telogen-anagen regeneration. Pairwise comparisons between the control and melatonin-treated groups also indicate 941 monthly differentially expressed genes (monthly DEGs). These monthly DEGs are mainly distributed from April and September, which reveal a potential signal pathway map regulating the anagen stage triggered by melatonin. Enrichment analysis shows that Wnt, Hedgehog, ECM, Chemokines and NF-kappa B signaling pathways may be involved in the regulation of non-quiescence and secondary shedding under the influence of melatonin. Conclusions Our study decodes the key regulators of the whole cashmere growth cycle, laying the foundation for the control of cashmere growth and improvement of cashmere yield.

SYSTEMATIC VARIATION NORMALIZATION IN MICROARRAY DATA TO GET GENE EXPRESSION COMPARISON UNBIASED

2005 ◽  
Vol 03 (02) ◽  
pp. 225-241 ◽  
Author(s):  
JEFF W. CHOU ◽  
RICHARD S. PAULES ◽  
PIERRE R. BUSHEL
Keyword(s):  
Gene Expression ◽  
Linear Regression ◽  
Microarray Data ◽  
Expression Patterns ◽  
Microarray Gene Expression Data ◽  
Systematic Variation ◽  
Data Sets ◽  
Microarray Gene Expression ◽  
Pixel Intensity ◽  
Non Linear

Normalization removes or minimizes the biases of systematic variation that exists in experimental data sets. This study presents a systematic variation normalization (SVN) procedure for removing systematic variation in two channel microarray gene expression data. Based on an analysis of how systematic variation contributes to variability in microarray data sets, our normalization procedure includes background subtraction determined from the distribution of pixel intensity values from each data acquisition channel and log conversion, linear or non-linear regression, restoration or transformation, and multiarray normalization. In the case when a non-linear regression is required, an empirical polynomial approximation approach is used. Either the high terminated points or their averaged values in the distributions of the pixel intensity values observed in control channels may be used for rescaling multiarray datasets. These pre-processing steps remove systematic variation in the data attributable to variability in microarray slides, assay-batches, the array process, or experimenters. Biologically meaningful comparisons of gene expression patterns between control and test channels or among multiple arrays are therefore unbiased using normalized but not unnormalized datasets.

scholarly journals Mechanisms driving endosperm-based hybrid incompatibilities: insights from hybrid monkeyflowers

2018 ◽  
Author(s):  
Taliesin J. Kinser ◽  
Ronald D. Smith ◽  
Amelia H. Lawrence ◽  
Arielle M. Cooley ◽  
Mario Vallejo-Marin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Genomic Imprinting ◽  
Parental Species ◽  
Expression Patterns ◽  
Naturally Occurring ◽  
Epigenetic Phenomenon ◽  
Underlying Mechanisms ◽  
Methylation Patterns ◽  
Regulatory Landscapes ◽  
Interspecies Hybrid

ABSTRACTAngiosperm endosperm requires genomic and epigenomic interactions between maternal and paternal genomes for proper seed development. Genomic imprinting, an epigenetic phenomenon where the expression of certain genes is predominantly contributed by one parent, is an essential part of this process and unique to endosperm. Perturbation of imprinting can be fatal to developing seeds, and can be caused by interspecific or interploidy hybridization. However, underlying mechanisms driving these endosperm-based hybridization barriers are not well understood or described. Here we investigate the consequences of genomic imprinting in a naturally occurring interploidy and interspecies hybrid between the diploid, Mimulus guttatus, and the allotetraploid (with two subgenomes), M. luteus (Phrymaceae). We find that the two parental species differ in patterns of DNA methylation, gene expression, and imprinting. Hybrid crosses in both directions, which suffer from endosperm abnormalities and decreased germination rates, display altered methylation patterns compared to parent endosperm. Furthermore, imprinting and expression patterns appear perturbed in hybrid endosperm, where we observe global expression dominance of each of the two M. luteus subgenomes, which share similar expression patterns, over the M. guttatus genome, regardless of crossing direction. We suggest that epigenetic repatterning within the hybrid may drive global shifts in expression patterns and be the result of diverged epigenetic/regulatory landscapes between parental genomes. This may either establish or exacerbate dosage-based epistatic incompatibilities between the specific imprinting patterns that have diverged between parental species, thus driving potentially rapid endosperm-based hybridization barriers.

scholarly journals Regulatory T Cell-Related Gene Biomarkers in the Deterioration of Atherosclerosis

2021 ◽  
Vol 8 ◽  
Author(s):  
Meng Xia ◽  
Qingmeng Wu ◽  
Pengfei Chen ◽  
Cheng Qian
Keyword(s):  
Gene Expression ◽  
Cardiovascular Events ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Expression Patterns ◽  
Interaction Network ◽  
Gene Signature ◽  
Smooth Muscle Contraction ◽  
Gene Expression Omnibus ◽  
Scoring Method

Background: Regulatory T cells (Tregs) have shown to be protective against the development of atherosclerosis, a major pathological cause for cardiovascular events. Here, we aim to explore the roles of Tregs-related genes in atherosclerosis deterioration.Methods and Results: We downloaded the gene expression profile of 29 atherosclerotic samples from the Gene Expression Omnibus database with an accession number of GSE28829. The abundance of Tregs estimated by the CIBERSORT algorithm was negatively correlated with the atherosclerotic stage. Using the limma test and correlation analysis, a total of 159 differentially expressed Tregs-related genes (DETregRGs) between early and advanced atherosclerotic plaques were documented. Functional annotation analysis using the DAVID tool indicated that the DETregRGs were mainly enriched in inflammatory responses, immune-related mechanisms, and pathways such as complement and coagulation cascades, platelet activation, leukocyte trans-endothelial migration, vascular smooth muscle contraction, and so on. A protein-protein interaction network of the DETregRGs was then constructed, and five hub genes (PTPRC, C3AR1, CD53, TLR2, and CCR1) were derived from the network with node degrees ≥20. The expression patterns of these hub DETregRGs were further validated in several independent datasets. Finally, a single sample scoring method was used to build a gene signature for the five DETregRGs, which could distinguish patients with myocardial infarction from those with stable coronary disease.Conclusion: The results of this study will improve our understanding about the Tregs-associated molecular mechanisms in the progression of atherosclerosis and facilitate the discovery of novel biomarkers for acute cardiovascular events.

scholarly journals Comparative Gene Expression Analysis Reveals Similarities and Differences of Chronic Myeloid Leukemia Phases

Cancers ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 256
Author(s):  
Annemarie Schwarz ◽  
Ingo Roeder ◽  
Michael Seifert
Keyword(s):  
Gene Expression ◽  
Chronic Myeloid Leukemia ◽  
Signaling Pathway ◽  
Myeloid Leukemia ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Chronic Phase ◽  
Receptor Interaction ◽  
Similarities And Differences

Chronic myeloid leukemia (CML) is a slowly progressing blood cancer that primarily affects elderly people. Without successful treatment, CML progressively develops from the chronic phase through the accelerated phase to the blast crisis, and ultimately to death. Nowadays, the availability of targeted tyrosine kinase inhibitor (TKI) therapies has led to long-term disease control for the vast majority of patients. Nevertheless, there are still patients that do not respond well enough to TKI therapies and available targeted therapies are also less efficient for patients in accelerated phase or blast crises. Thus, a more detailed characterization of molecular alterations that distinguish the different CML phases is still very important. We performed an in-depth bioinformatics analysis of publicly available gene expression profiles of the three CML phases. Pairwise comparisons revealed many differentially expressed genes that formed a characteristic gene expression signature, which clearly distinguished the three CML phases. Signaling pathway expression patterns were very similar between the three phases but differed strongly in the number of affected genes, which increased with the phase. Still, significant alterations of MAPK, VEGF, PI3K-Akt, adherens junction and cytokine receptor interaction signaling distinguished specific phases. Our study also suggests that one can consider the phase-wise CML development as a three rather than a two-step process. This is in accordance with the phase-specific expression behavior of 24 potential major regulators that we predicted by a network-based approach. Several of these genes are known to be involved in the accumulation of additional mutations, alterations of immune responses, deregulation of signaling pathways or may have an impact on treatment response and survival. Importantly, some of these genes have already been reported in relation to CML (e.g., AURKB, AZU1, HLA-B, HLA-DMB, PF4) and others have been found to play important roles in different leukemias (e.g., CDCA3, RPL18A, PRG3, TLX3). In addition, increased expression of BCL2 in the accelerated and blast phase indicates that venetoclax could be a potential treatment option. Moreover, a characteristic signaling pathway signature with increased expression of cytokine and ECM receptor interaction pathway genes distinguished imatinib-resistant patients from each individual CML phase. Overall, our comparative analysis contributes to an in-depth molecular characterization of similarities and differences of the CML phases and provides hints for the identification of patients that may not profit from an imatinib therapy, which could support the development of additional treatment strategies.

scholarly journals Effect of LAMA4 on Prognosis and Its Correlation with Immune Infiltration in Gastric Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Mingming Wang ◽  
Changzheng Li ◽  
Ying Liu ◽  
Zuomin Wang
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Immune Cell ◽  
Expression Patterns ◽  
Disease Free Survival ◽  
Genetic Alterations ◽  
Clinicopathological Characteristics ◽  
Basement Membranes ◽  
The Cancer Genome Atlas ◽  
Receptor Interaction

Background. Laminin alpha 4 (LAMA4) is widely distributed in the basement membranes of various tissues. It can regulate cancer cell proliferation and migration. We investigated the effects of LAMA4 in gastric cancer (GC). Methods. LAMA4 expression patterns were analyzed in GC using the Gene Expression Omnibus (GEO), Gene Expression Profiling Interactive Analysis (GEPIA), and UALCAN. Correlations between LAMA4 expression and clinicopathological characteristics were evaluated using data from The Cancer Genome Atlas (TCGA). The survival analysis was examined using the Kaplan-Meier plotter and GEPIA and ascertained by multivariate Cox analysis. Genetic alterations and DNA methylation of LAMA4 were analyzed using cBioPortal and MethSurv. LinkedOmics was applied to identify coexpressed genes of LAMA4. The association between LAMA4 and infiltration of immune cells was explored using Tumor Immune Estimation Resource (TIMER) and GEPIA. Results. LAMA4 was highly expressed in GC, and its upregulation significantly correlated with T classification ( P = 0.040 ). LAMA4 expression was an independent risk factor for overall survival (OS, P = 0.033 ). Patients with genetic alterations of LAMA4 showed a significantly better disease-free survival (DFS, P = 0.022 ). Ten CpG sites of LAMA4 were significantly associated with prognosis in GC. The functions of LAMA4 and coexpression genes were mainly involved in extracellular matrix (ECM) receptor interaction. LAMA4 expression significantly correlated with infiltration of macrophages ( P < 0.001 ), CD4+ T cells ( P < 0.001 ), and dendritic cells ( P < 0.001 ). Furthermore, LAMA4 expression was significantly associated with markers of M2 and tumor-associated macrophages (TAMs). Conclusion. LAMA4 expression was linked to GC prognosis and immune cell infiltration, indicating its potential use as a prognostic biomarker and therapeutic target.

scholarly journals Quantitative comparison of the anterior-posterior patterning system in the embryos of five Drosophila species

2018 ◽  
Author(s):  
Zeba Wunderlich ◽  
Charless C. Fowlkes ◽  
Kelly B. Eckenrode ◽  
Meghan D. J. Bragdon ◽  
Arash Abiri ◽  
...  
Keyword(s):  
Gene Expression ◽  
Regulatory Networks ◽  
Expression Patterns ◽  
Evolutionary Developmental Biology ◽  
Drosophila Virilis ◽  
Gene Expression Patterns ◽  
Data Sets ◽  
Developmental Gene ◽  
Regulatory Dna ◽  
Anterior Posterior

AbstractComplex spatiotemporal gene expression patterns direct the development of the fertilized egg into an adult animal. Comparisons across species show that, in spite of changes in the underlying regulatory DNA sequence, developmental programs can be maintained across millions of years of evolution. Reciprocally, changes in gene expression can be used to generate morphological novelty. Distinguishing between changes in regulatory DNA that lead to changes in gene expression and those that do not is therefore a central goal of evolutionary developmental biology. Quantitative, spatially-resolved measurements of developmental gene expression patterns play a crucial role in this goal, enabling the detection of subtle phenotypic differences between species and the development of computations models that link the sequence of regulatory DNA to expression patterns. Here we report the generation of two atlases of cellular resolution gene expression measurements for the primary anterior-posterior patterning genes in Drosophila simulans and Drosophila virilis. By combining these data sets with existing atlases for three other Drosophila species, we detect subtle differences in the gene expression patterns and dynamics driving the highly conserved axis patterning system and delineate inter-species differences in the embryonic morphology. These data sets will be a resource for future modeling studies of the evolution of developmental gene regulatory networks.

scholarly journals Analysis of Pir Gene Expression Across the Plasmodium Life Cycle

2021 ◽  
Author(s):  
Timothy S. Little ◽  
Deirdre A. Cunningham ◽  
Audrey Vandomme ◽  
Carlos Talavera Lopez ◽  
Sarah I. Amis ◽  
...  
Keyword(s):  
Gene Expression ◽  
Life Cycle ◽  
Antigenic Variation ◽  
Expression Patterns ◽  
Plasmodium Species ◽  
Data Sets ◽  
Life Cycle Stages ◽  
Determine Function ◽  
Gene Expression Studies ◽  
Functional Investigation

Abstract Background Plasmodium interspersed repeat ( pir ) is the largest multigene family in the genomes of most Plasmodium species. A variety of functions for the PIR proteins which they encode have been proposed, including antigenic variation, immune evasion, sequestration and rosetting. However, direct evidence for these is lacking. The repetitive nature of the family has made it difficult to determine function experimentally. However, there has been some success in using gene expression studies to suggest roles for some members in virulence and chronic infection. Methods Here we examined pir gene expression across the life cycle of P. berghei using publicly available RNAseq data-sets, and at high resolution in the intraerythrocytic development cycle using new data from P. chabaudi . Results Expression of pir genes is greatest in stages of the parasite which invade and reside in red blood cells. The marked exception is that liver merozoites and male gametocytes produce a very large number of pir gene transcripts, notably compared to female gametocytes, which produce relatively few. Within the asexual blood stages different subfamilies peak at different times, suggesting further functional distinctions. Representing a subfamily of its own, the highly conserved ancestral pir gene warrants further investigation due to its potential tractability for functional investigation. It is highly transcribed in multiple life cycle stages and across most studied Plasmodium species and thus is likely to play an important role in parasite biology. Conclusions By identifying distinct expression patterns for different pir genes and subfamilies we hope to provide a basis for the design of future experiments to uncover their function.

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