scholarly journals Multiomics Analysis of Transcriptome, Epigenome, and Genome Uncovers Putative Mechanisms for Dilated Cardiomyopathy

2021 ◽  
Vol 2021 ◽  
pp. 1-29
Author(s):  
Li Liu ◽  
Jianjun Huang ◽  
Yan Liu ◽  
Xingshou Pan ◽  
Zhile Li ◽  
...  
Keyword(s):  
Dilated Cardiomyopathy ◽  
Differentially Expressed ◽  
Molecular Characteristics ◽  
Rna Seq ◽  
Frequent Mutation ◽  
Protein Protein Interaction ◽  
Molecular Features ◽  
Differentially Methylated Genes ◽  
And Control ◽  
Control Samples

Objective. Multiple genes have been identified to cause dilated cardiomyopathy (DCM). Nevertheless, there is still a lack of comprehensive elucidation of the molecular characteristics for DCM. Herein, we aimed to uncover putative molecular features for DCM by multiomics analysis. Methods. Differentially expressed genes (DEGs) were obtained from different RNA sequencing (RNA-seq) datasets of left ventricle samples from healthy donors and DCM patients. Furthermore, protein-protein interaction (PPI) analysis was then presented. Differentially methylated genes (DMGs) were identified between DCM and control samples. Following integration of DEGs and DMGs, differentially expressed and methylated genes were acquired and their biological functions were analyzed by the clusterProfiler package. Whole exome sequencing of blood samples from 69 DCM patients was constructed in our cohort, which was analyzed the maftools package. The expression of key mutated genes was verified by three independent datasets. Results. 1407 common DEGs were identified for DCM after integration of the two RNA-seq datasets. A PPI network was constructed, composed of 171 up- and 136 downregulated genes. Four hub genes were identified for DCM, including C3 ( degree = 24 ), GNB3 ( degree = 23 ), QSOX1 ( degree = 21 ), and APOB ( degree = 17 ). Moreover, 285 hyper- and 321 hypomethylated genes were screened for DCM. After integration, 20 differentially expressed and methylated genes were identified, which were associated with cell differentiation and protein digestion and absorption. Among single-nucleotide variant (SNV), C>T was the most frequent mutation classification for DCM. MUC4 was the most frequent mutation gene which occupied 71% across 69 samples, followed by PHLDA1, AHNAK2, and MAML3. These mutated genes were confirmed to be differentially expressed between DCM and control samples. Conclusion. Our findings comprehensively analyzed molecular characteristics from the transcriptome, epigenome, and genome perspectives for DCM, which could provide practical implications for DCM.

Suppressed Immune-Related Profile Rescues Abortion-Prone Fetuses: A Novel Insight Into the CBA/J × DBA/2J Mouse Model

2019 ◽  
Vol 26 (11) ◽  
pp. 1485-1492
Author(s):  
Xiaochun Yi ◽  
Jie Zhang ◽  
Huixiang Liu ◽  
Tianxia Yi ◽  
Yuhua Ou ◽  
...  
Keyword(s):  
Immune System ◽  
Differentially Expressed ◽  
Rna Seq ◽  
Poor Treatment ◽  
Polymerase Chain ◽  
Poor Treatment Outcome ◽  
Immune Related Genes ◽  
And Control ◽  
Upregulated Genes ◽  
Tgf Β1

The adverse clinical result and poor treatment outcome in recurrent spontaneous abortion (RSA) make it necessary to understand the pathogenic mechanism. The mating combination CBA/J × DBA/2 has been widely used as an abortion-prone model compared to DBA/2-mated CBA/J mice. Here, we used RNA-seq to get a comprehensive catalogue of genes differentially expressed between survival placenta in abortion-prone model and control. Five hundred twenty-four differentially expressed genes were obtained followed by clustering analysis, Gene Ontology analysis, and pathway analysis. We paid more attention to immune-related genes namely “immune response” and “immune system process” including 33 downregulated genes and 28 upregulated genes. Twenty-one genes contribute to suppressing immune system and 7 are against it. Six genes were validated by reverse transcription-polymerase chain reaction, namely Ccr1l1, Tlr4, Tgf-β1, Tyro3, Gzmb, and Il-1β. Furthermore, Tlr4, Tgf-β1, and Il-1β were analyzed by Western blot. Such immune profile gives us a better understanding of the complicated immune processing in RSA and immunosuppression can rescue pregnancy loss.

scholarly journals Identification of microRNAs and genes as biomarkers of atrial fibrillation using a bioinformatics approach

2019 ◽  
Vol 47 (8) ◽  
pp. 3580-3589 ◽  
Author(s):  
Yingyuan Li ◽  
Wulin Tan ◽  
Fang Ye ◽  
Faling Xue ◽  
Shaowei Gao ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Target Genes ◽  
Enrichment Analysis ◽  
Gene Expression Omnibus ◽  
Differentially Expressed ◽  
Control Groups ◽  
Protein Protein Interaction ◽  
Differentially Expressed Mirnas ◽  
Software Modules ◽  
And Control

Objective We aimed to explore potential microRNAs (miRNAs) and target genes related to atrial fibrillation (AF). Methods Data for microarrays GSE70887 and GSE68475, both of which include AF and control groups, were downloaded from the Gene Expression Omnibus database. Differentially expressed miRNAs between AF and control groups were identified within each microarray, and the intersection of these two sets was obtained. These miRNAs were mapped to target genes in the miRNet database. Functional annotation and enrichment analysis of these target genes was performed in the DAVID database. The protein-protein interaction (PPI) network from the STRING database and the miRNA-target-gene network were merged into a PPI-miRNA network using Cytoscape software. Modules of this network containing miRNAs were detected and further analyzed. Results Ten differentially expressed miRNAs and 1520 target genes were identified. Three PPI-miRNA modules were constructed, which contained miR-424, miR-15a, miR-542-3p, and miR-421 as well as their target genes, CDK1, CDK6, and CCND3. Conclusion The identified miRNAs and genes may be related to the pathogenesis of AF. Thus, they may be potential biomarkers for diagnosis and targets for treatment of AF.

scholarly journals Dysregulation of Placental Functions and Immune Pathways in Complete Hydatidiform Moles

2019 ◽  
Vol 20 (20) ◽  
pp. 4999 ◽  
Author(s):  
Jennifer R. King ◽  
Melissa L. Wilson ◽  
Szabolcs Hetey ◽  
Peter Kiraly ◽  
Koji Matsuo ◽  
...  
Keyword(s):  
Gene Expression ◽  
First Trimester ◽  
Receptor Interaction ◽  
Rna Seq ◽  
Bioinformatics Analyses ◽  
Immune Genes ◽  
Molecular Features ◽  
Immune Pathways ◽  
And Control ◽  
Hydatidiform Moles

Gene expression studies of molar pregnancy have been limited to a small number of candidate loci. We analyzed high-dimensional RNA and protein data to characterize molecular features of complete hydatidiform moles (CHMs) and corresponding pathologic pathways. CHMs and first trimester placentas were collected, histopathologically examined, then flash-frozen or paraffin-embedded. Frozen CHMs and control placentas were subjected to RNA-Seq, with resulting data and published placental RNA-Seq data subjected to bioinformatics analyses. Paraffin-embedded tissues from CHMs and control placentas were used for tissue microarray (TMA) construction, immunohistochemistry, and immunoscoring for galectin-14. Of the 14,022 protein-coding genes expressed in all samples, 3,729 were differentially expressed (DE) in CHMs, of which 72% were up-regulated. DE genes were enriched in placenta-specific genes (OR = 1.88, p = 0.0001), of which 79% were down-regulated, imprinted genes (OR = 2.38, p = 1.54 × 10−6), and immune genes (OR = 1.82, p = 7.34 × 10−18), of which 73% were up-regulated. DNA methylation-related enzymes and histone demethylases were dysregulated. “Cytokine–cytokine receptor interaction” was the most impacted of 38 dysregulated pathways, among which 17 were immune-related pathways. TMA-based immunoscoring validated the lower expression of galectin-14 in CHM. In conclusion, placental functions were down-regulated, imprinted gene expression was altered, and immune pathways were activated, indicating complex dysregulation of placental developmental and immune processes in CHMs.

scholarly journals Construction and Comprehensive Analysis of Dysregulated Long Noncoding RNA-Associated Competing Endogenous RNA Network in Moyamoya Disease

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Xuefeng Gu ◽  
Dongyang Jiang ◽  
Yue Yang ◽  
Peng Zhang ◽  
Guoqing Wan ◽  
...  
Keyword(s):  
Moyamoya Disease ◽  
Cerebral Artery ◽  
Regulatory Network ◽  
Noncoding Rna ◽  
Expression Profiles ◽  
Differentially Expressed ◽  
Competing Endogenous Rna ◽  
Cerna Network ◽  
And Control ◽  
Control Samples

Background. Moyamoya disease (MMD) is a rare cerebrovascular disease characterized by chronic progressive stenosis or occlusion of the bilateral internal carotid artery (ICA), the anterior cerebral artery (ACA), and the middle cerebral artery (MCA). MMD is secondary to the formation of an abnormal vascular network at the base of the skull. However, the etiology and pathogenesis of MMD remain poorly understood. Methods. A competing endogenous RNA (ceRNA) network was constructed by analyzing sample-matched messenger RNA (mRNA), long non-coding RNA (lncRNA), and microRNA (miRNA) expression profiles from MMD patients and control samples. Then, a protein-protein interaction (PPI) network was constructed to identify crucial genes associated with MMD. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were employed with the DAVID database to investigate the underlying functions of differentially expressed mRNAs (DEmRNAs) involved in the ceRNA network. CMap was used to identify potential small drug molecules. Results. A total of 94 miRNAs, 3649 lncRNAs, and 2294 mRNAs were differentially expressed between MMD patients and control samples. A synergistic ceRNA lncRNA-miRNA-mRNA regulatory network was constructed. Core regulatory miRNAs (miR-107 and miR-423-5p) and key mRNAs (STAT5B, FOSL2, CEBPB, and CXCL16) involved in the ceRNA network were identified. GO and KEGG analyses indicated that the DEmRNAs were involved in the regulation of the immune system and inflammation in MMD. Finally, two potential small molecule drugs, CAY-10415 and indirubin, were identified by CMap as candidate drugs for treating MMD. Conclusions. The present study used bioinformatics analysis of candidate RNAs to identify a series of clearly altered miRNAs, lncRNAs, and mRNAs involved in MMD. Furthermore, a ceRNA lncRNA-miRNA-mRNA regulatory network was constructed, which provides insights into the novel molecular pathogenesis of MMD, thus giving promising clues for clinical therapy.

scholarly journals A Novel Competing Endogenous RNA Network Associated With the Pathogenesis of Graves’ Ophthalmopathy

2021 ◽  
Vol 12 ◽  
Author(s):  
Zifan Yue ◽  
Pei Mou ◽  
Sainan Chen ◽  
Fei Tong ◽  
Ruili Wei
Keyword(s):  
High Throughput Sequencing ◽  
Circular Rna ◽  
Differentially Expressed ◽  
Autoimmune Response ◽  
Sequence Matching ◽  
Competing Endogenous Rna ◽  
Protein Protein Interaction ◽  
Cerna Network ◽  
Graves Ophthalmopathy ◽  
And Control

Background: Growing evidence has recently revealed the characteristics of long noncoding (lncRNA)/circular RNA (circRNA)-microRNA (miRNA)-mRNA networks in numerous human diseases. However, a scientific lncRNA/circRNA-miRNA-mRNA network related to Graves’ ophthalmopathy (GO) remains lacking.Materials and methods: The expression levels of RNAs in GO patients were measured through high-throughput sequencing technology, and the results were proven by quantitative real-time PCR (qPCR). We constructed a protein-protein interaction (PPI) network using the Search Tool for the Retrieval of Interacting Genes (STRING) database and identified hub genes by the Cytoscape plug-in CytoHubba. Then, the miRNAs related to differentially expressed lncRNAs/circRNAs and mRNAs were predicted through seed sequence matching analysis. Correlation coefficient analysis was performed on the interesting RNAs to construct a novel competing endogenous RNA (ceRNA) network.Results: In total, 361 mRNAs, 355 circRNAs, and 242 lncRNAs were differentially expressed in GO patients compared with control patients, 166 pairs were identified, and ceRNA networks were constructed. The qPCR results showed that 4 mRNAs (THBS2, CHRM3, CXCL1, FPR2) and 2 lncRNAs (LINC01820:13, ENST00000499452) were differentially expressed between the GO patients and control patients.Conclusion: An innovative lncRNA/circRNA-miRNA-mRNA ceRNA network between GO patients and control patients was constructed, and two important ceRNA pathways were identified, the LINC01820:13-hsa-miR-27b-3p-FPR2 ceRNA pathway and the ENST00000499452-hsa-miR-27a-3p-CXCL1 pathway, which probably affect the autoimmune response and inflammation in GO patients.

Proximal and distal colon tumors as distinct biologic entities with different prognoses.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3526-3526 ◽  
Author(s):  
Edoardo Missiaglia ◽  
Bart Jacobs ◽  
Antonio Fabio Di Narzo ◽  
Charlotte Soneson ◽  
Arnaud Roth ◽  
...  
Keyword(s):  
Distal Colon ◽  
Hepatic Flexure ◽  
Differentially Expressed ◽  
Molecular Characteristics ◽  
Normal Colon ◽  
Mucinous Histology ◽  
Pik3ca Mutations ◽  
Therapeutic Implications ◽  
Colon Tumors ◽  
Molecular Features

3526 Background: It has been shown that tumors arising in the proximal and distal colon, defined by the embryological midgut and hindgut, have distinctive clinical and molecular features, but very little is known concerning the differences in the mechanism of tumorigenesis and the effect that this could have on therapy. Methods: The distribution of clinico-pathological and molecular features was evaluated between proximal (N = 1110, Caecum to hepatic flexure) and distal colon (N = 1728, splenic flexure down to sigmoid) in patients included in the PETACC3 trial. Gene expression profile was also available from 783 tumors and 32 normal colon. A further set of 473 metastatic patients treated with cetuximab combined with chemotherapy (De Roock Lancet Oncol. 2010) was used to test tumor location with response. Results: Pathological features, such as tumor differentiation, and mucinous histology as well as molecular characteristics, such as MSI status, BRAF, PIK3Ca mutations and LOH18q loss show higher frequency in proximal compared to distal colon (N = 1214; Fisher test, P<0.001). Proximal tumors showed a significantly worse overall survival (N= 2838; HR=1.4 [1.18 - 1.64] P<0.001) and survival after relapse (N = 861; HR=1.97 [1.65 - 2.35] P <0.001) only if they were stage III at diagnosis, while no difference was observed for relapse free survival. Microarray profiling identified 997 genes differentially expressed between the two anatomical sites, after adjustment for age, gender, mucinous histology, BRAF, KRAS and MSI status. Only 20 of those were present in normal colon site comparison indicating tumor specificity. Data mining analysis of the differentially expressed genes showed that the distal colon is characterized by an enrichment for MAPK activated pathways as well as for the cetuximab response gene signature (Khambata-Ford JCO 2007). In fact, cetuximab treated KRAS/BRAF wild-type tumors in distal colon had prolonged PFS and a 2-fold higher response rate then proximal. Conclusions: Proximal and distal colon tumors have distinctive patterns of clinical-pathological and molecular features. These biological differences likely have significant prognostic and therapeutic implications.

scholarly journals Transcriptional Regulation of lncRNA Genes by Histone Modification in Alzheimer’s Disease

2016 ◽  
Vol 2016 ◽  
pp. 1-4 ◽  
Author(s):  
Guoqiang Wan ◽  
Wenyang Zhou ◽  
Yang Hu ◽  
Rui Ma ◽  
Shuilin Jin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Histone Modification ◽  
Noncoding Rnas ◽  
Differentially Expressed ◽  
Biological Processes ◽  
Rna Seq ◽  
Wide Range ◽  
And Control ◽  
Histone Modification Data

Increasing studies have revealed that long noncoding RNAs (lncRNAs) are not transcriptional noise but play important roles in the regulation of a wide range of biological processes, and the dysregulation of lncRNA genes is associated with disease development. Alzheimer’s disease (AD) is a chronic neurodegenerative disease that usually starts slowly and gets worse over time. However, little is known about the roles of lncRNA genes in AD and how the lncRNA genes are transcriptionally regulated. Herein, we analyzed RNA-seq data and ChIP-seq histone modification data from CK-p25 AD model and control mice and identified 72 differentially expressed lncRNA genes, 4,917 differential peaks of H3K4me3, and 1,624 differential peaks of H3K27me3 between AD and control samples, respectively. Furthermore, we found 92 differential peaks of histone modification H3K4me3 are located in the promoter of 39 differentially expressed lncRNA genes and 8 differential peaks of histone modification H3K27me3 are located upstream of 7 differentially expressed lncRNA genes, which suggest that the majority of lncRNA genes may be transcriptionally regulated by histone modification in AD.

scholarly journals Use of RNA-seq to identify cardiac genes and gene pathways differentially expressed between dogs with and without dilated cardiomyopathy

2016 ◽  
Vol 77 (7) ◽  
pp. 693-699 ◽  
Author(s):  
Steven G. Friedenberg ◽  
Lhoucine Chdid ◽  
Bruce Keene ◽  
Barbara Sherry ◽  
Alison Motsinger-Reif ◽  
...  
Keyword(s):  
Dilated Cardiomyopathy ◽  
Differentially Expressed ◽  
Rna Seq

scholarly journals N6-Methyladenosine Modification Changes in the Genome of Paulownia Fortunei Seedlings Infected With Phytoplasma

2022 ◽  
Author(s):  
Pingluo Xu ◽  
Shunmou Huang ◽  
Xiaoqiao Zhai ◽  
Xiaofan Li ◽  
Haibo Yang ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Receptor Protein ◽  
Economic Losses ◽  
Rna Seq ◽  
Differentially Methylated Genes ◽  
Paulownia Fortunei

Abstract Background: Phytoplasmas induce diseases in more than 1,000 plant species and cause substantial ecological damage and economic losses, but the specific pathogenesis of phytoplasma has not yet been clarified. N6-methyladenosine sequencing (m6A-seq) has been applied mainly to model plants and not to woody plants. Results: In this study, we applied m6A-seq to study changes in m6A modification in the Paulownia fortunei genome after phytoplasma infection. We found that the m6A modification level in seedlings infected with the phytoplasma that causes Paulownia witches' broom (PaWB) was slightly higher than the m6A modification level in PaWB-infected seedlings treated with 60 mg·L−1 methyl methanesulfonate (MMS). MMS has been shown to restore PaWB-infected seedlings to their normal form and no phytoplasma can be detected in MMS-treated PaWB-infected seedlings. RNA sequencing (RNA-seq) and m6A-seq were used to analyze the expression of genes with m6A peaks and m6A motifs in genes, respectively. The correlation analysis between the RNA-seq and m6A-seq data detected that a total of 315 differentially methylated genes were predicted to be significantly differentially expressed at the transcriptome level. The functions of genes related to PaWB were predicted by functional enrichment analysis, and two genes related to maintenance of the basic mechanism of stem cells in shoot apical meristem were discovered. One of the genes encodes the receptor protein kinase CLV2 (Paulownia_LG2G000076), and the other gene encodes the homeobox transcription factor STM (Paulownia_LG15G000976). The m6A modification levels were higher in PaWB-infected seedlings than they were in MMS-treated seedlings. In addition, genes F-box (Paulownia_LG17G000760) and MSH5 (Paulownia_LG8G001160) had exon skipping and mutually exclusive exon types of alternative splicing in PaWB-infected seedling treated with MMS. RT-PCR verified that the alternative splicing of these two genes was related to m6A modification. Conclusions: In this study, we applied m6A-seq to determine methylation levels in phytoplasma-infected Paulownia, and combined m6A-seq with transcriptome analysis to screen differentially expressed genes associated with PaWB. Also analyzed the effect of m6A methylation on alternative splicing. In future studies, we plan to verify genes directly related to PaWB and methylation-related enzymes in Paulownia to elucidate the pathogenicity mechanism of PaWB caused by phytoplasma invasion.

Intrinsic Molecular Characteristics of the Immune Subtypes of Salivary Mucoepidermoid Carcinoma

2021 ◽  
Author(s):  
Hyundeok Kang ◽  
Mi-Kyoung Seo ◽  
BeumJin Park ◽  
Yoon Woo Koh ◽  
Dahee Kim ◽  
...  
Keyword(s):  
Mucoepidermoid Carcinoma ◽  
Treatment Options ◽  
Inverse Correlation ◽  
Molecular Characteristics ◽  
Rna Seq ◽  
Molecular Features ◽  
Mutational Burden ◽  
Tumor Mutational Burden ◽  
First Time ◽  
Metabolic Regulators

Abstract Background: Characterising the tumor microenvironment (TME) and immune landscape of cancer has been a promising step towards discovering new therapeutic biomarkers and guiding precision medicine; however, its application in salivary mucoepidermoid carcinoma (MEC) has been sparse. Here, we conducted a comprehensive transcriptomic study to understand the properties of the TME and immune profiles of MEC.Methods: Molecular features in heterogeneous immunophenotypic subgroups of MEC and their intrinsic characteristics were determined by applying bioinformatic and immunoinformatic analyses on 20 matched primary MEC RNA-seq data.Results: In this study, distinct two immunophenotypic subgroups, hot and cold MECs, were uncovered with their distinct molecular features, and potential immune-oncologic therapeutic options for each subgroup were suggested. In search for immunophenotype defining molecular features, tumor mutational burden, CRTC1-MAML2 fusion status, and its fusion neoantigen were not discriminable factors. However, we demonstrate that a significant inverse correlation between lipid metabolism activity and immunogenic state, and lipid metabolic regulators, such as MLXIPL and FASN, which are associated suppression of immune activity, were under-expressed in the immune-hot subgroup, contributing significant role in high immunity of immune active subgroup.Conclusions: Our study has shown heterogeneous immunophenotypic MEC subgroups with their distinctive molecular characteristics and provided potential treatment options tailored to the immune context, which yields, for the first time, new insights into TME of MEC and may help the next step to studying this uncharted cancer.

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