scholarly journals Identification of Novel Fusion Genes and Differentially Expressed Genes in Acute Leukemia through Transcriptome Analysis

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1220-1220
Author(s):  
Dong-Hyun Lee ◽  
Young-Uk Cho ◽  
Seongsoo Jang ◽  
Chan-Jeoung Park ◽  
Mi Hyun Bae ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Leukemia ◽  
Rna Sequencing ◽  
Differentially Expressed Genes ◽  
Fusion Transcript ◽  
Differentially Expressed ◽  
Fusion Genes ◽  
Next Generation ◽  
Fusion Transcripts ◽  
Novel Transcript

Abstract Background Chromosomal translocations in acute leukemia frequently result in gene fusions that are associated with leukemogenesis. Next-generation sequencing technology has opened up a systematic characterization of transcriptomes including gene expression, novel transcript, and fusion transcripts. We used next-generation RNA sequencing to identify fusion genes responsible for novel chromosomal translocations in acute leukemia and to find their differentially expressed genes. Methods We selected 10 acute leukemia (AML, 6; B-ALL, 3; and T-ALL, 1) patients with novel translocations by G-banding. Total RNA was extracted from leukemia cells and cDNA libraries were constructed with TruSeq RNA kit. Paired-end sequencing was performed on HiSeq2500. Reads were aligned with TopHat/BowTie, and deFuse was used to detect fusion transcripts. Transcript assembly and abundance estimation were done using Cufflinks, and expression levels were quantified by fragments per kilobase of transcript per million mapped reads (FPKM). The candidate fusion transcripts were validated with fluorescence in situ hybridization (FISH), and reverse-transcription PCR followed by Sanger-sequencing. Results We found 5 in-frame fusion genes exactly matched on translocation breakpoints from 3 AML patients and 1 B-ALL patient: USP34-ASAP3/t(1;2)(p36.1;p11.2), MAZ-MKL1/t(16;22)(p11.2;q13), MLL-SEPT6 and SEPT6-CDCA5/t(X;11)(q24;q13), and RCSD1-ABL1/t(1;9)(q24;q34). The USP34-ASAP3 fusion produced a novel transcript between USP34 exon 2 and ASAP3 exon 18. The protein encoded by the ASAP3 gene promotes cell differentiation and migration and has been implicated in cancer cell invasion. Comparing gene expression in this sample to nine other samples, we found six overexpressed genes; CLEC3B, SNAR-A14, H19, HOTS, SNORD35A, and S100A1. CLEC3B is associated with human disorders affecting bone and connective tissue. H19 is located in an imprinted region of chromosome 11 and is associated with Wilms tumorigenesis. S100A1 is involved in the regulation of a number of cellular processes such as cell cycle progression and differentiation. The MAZ-MKL1 fusion transcript was composed of MAZ exon 4 and MKL1 exon 4. MAZ was a novel partner gene of MKL1 which had been reported in acute megakaryoblastic leukemia carrying RBM15-MKL1/t(1;22)(p13;q13). MS4A2, RPLP0, and ARP5J2 genes were overexpressed in this rearrangement. MS4A2 is related PI3K cascade pathway and immune response pathway. RPLP0 is responsible for RNA binding and structural constituent of ribosome. AML patient with t(X;11)(q24;q13) had two fusion transcripts, MLL-SEPT6 and SEPT6-CDCA5 resulting from complex MLL rearrangement. While the MLL-SEPT6 fusion has been known in AML cases, the SEPT6-CDCA5 was a novel fusion. SNORD88B, MYL6, PTMA, MKX, NDUFAF3, and CNTN1 gene were more highly expressed than other samples. Among them, MKX and CNTN1 genes are related with cell adhesion function. The RCSD1-ABL1/t(1;9)(q24;q34) in B-ALL was previously reported to encode an aberrant tyrosine kinase. This translocation had also reciprocal ABL1-RCSD1 fusion transcript which could result in an alteration of cellular function. Six genes were specifically overexpressed in this sample RCBTB2, SERHL2, MIR941-2, FAM150B, GPR110, and SNORA27. RCBTB2 encodes a protein that is related to regulator of chromosome condensation. We also investigated leukemia subtype-specific expression profiles. The five significant genes were higher expressed in AML as compared with ALL (MIR4461, SET, RNU6ATAC, NINJ2, and ATP6V0C). Especially, MIR4461 was over 6000 FPKM in 5 of 6 AML samples, but was never expressed in ALL samples. B-ALL specific overexpressed genes were C17orf62, and MIR941-1, whereas T-ALL specific overexpressed gene was SNORD33. Conclusions Using next-generation RNA sequencing, we have discovered 5 candidate fusion genes in 10 acute leukemia patients with novel translocations, and identified 3 novel fusion genes to be predicted as oncogenic potential. Through the comparison of expression profiling, we were able to define differentially expressed genes in acute leukemia with novel fusion genes and leukemia subtype-specific gene expression. RNA-sequencing is a powerful tool for the discovery of leukemia-associated fusion genes and their related genes as well as molecular pathways. Disclosures No relevant conflicts of interest to declare.

scholarly journals NUTM1 Is a Rare but Recurrent Fusion Gene Partner in B Cell Precursor Acute Lymphoblastic Leukemia Associated with Increased Expression of Genes on Cytoband 10p12.31

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2823-2823
Author(s):  
Femke M. Hormann ◽  
Alex Q. Hoogkamer ◽  
H. Berna Beverloo ◽  
Aurélie Boeree ◽  
Ronald W. Stam ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Lymphoblastic Leukemia ◽  
Rna Sequencing ◽  
Histone Acetyltransferase ◽  
Lymphoblastic Leukemia ◽  
Fusion Transcript ◽  
Population Based ◽  
Fusion Genes ◽  
Cell Precursor ◽  
Cytogenetic Aberration

Abstract INTRODUCTION In 20-25% of the pediatric B cell precursor acute lymphoblastic leukemia (BCP-ALL) patients, the driving cytogenetic aberration is unknown. It is important to identify more primary lesions in this remaining B-other group to provide better risk stratification and identify possible treatment options. In this study, we aimed to identify novel recurrent fusion genes in BCP-ALL through RNA sequencing. METHODS We used paired-end total RNA Illumina sequencing to detect fusion genes with STAR-fusion and FusionCatcher in a population-based ALL cohort (n=71). We used Affymetrix U133 Plus2 expression arrays in a larger population-based ALL cohort (n=661) and an infant ALL cohort (n=70) to compare gene expression levels. Fluorescent in situ hybridization (FISH) was performed using Cytocell NUTM1 break-apart probe set MPH4800. RESULTS We identified an in-frame SLC12A6-NUTM1 fusion transcript composed of exons 1-2 of SLC12A6 fused to exons 3 to 8 of NUTM1 by RNA sequencing. Both genes are located on 15q14 within 5.3 Kb distance on opposite strands, and the fusion could result from an inversion. The fusion transcript is predicted to encode almost the total NUTM1 protein including the acidic binding domain for the histone acetyltransferase EP300. The SLC12A6-NUTM1 fusion case showed high NUTM1 expression, while NUTM1 expression was absent in the remaining cases. Using gene expression profiling, we identified four additional pediatric and two non-KMT2A-rearranged infant BCP-ALL cases with high NUTM1 expression. In the population-based cohort reflecting all different cytogenetic subtypes, these cases were restricted to the B-other group without known sentinel cytogenetic abnormalities. FISH showed a NUTM1 break apart pattern in all four tested NUTM1-positive cases indicative of a balanced translocation. RNA sequencing confirmed an ACIN1-NUTM1 fusion in one of the infant cases. We conclude that NUTM1 is normally not expressed in leukemic lymphoblasts, and that its expression can be induced by a gene fusion. The karyotypes of the predicted NUTM1 fusion cases combined with RNA sequencing data suggest that different chromosomal rearrangements are involved, likely resulting in different NUTM1 fusion partners. In literature, BRD9-NUTM1, IKZF1-NUTM1, and CUX1-NUTM1 fusions were reported in pediatric B-other cases, and BRD9-NUTM1 and ACIN1-NUTM1 fusions were reported in non-KMT2A-rearranged infants. Our combined aberrant gene expression and FISH results indicate that NUTM1 fusions occur in 2.4% (5/210) of pediatric and in 28% (2/7) of infant BCP-ALL cases without a sentinel cytogenetic aberration. The recurrence of NUTM1 aberrations in BCP-ALL cases without a known driver and the resulting expression of NUTM1 suggests that this fusion could be a new oncogenic driver in leukemia. All seven patients with a NUTM1 fusion achieved continuous complete remission with a median follow-up time of 8.3 years (range 4.8-13.8 years), suggesting that NUTM1 fusions in BCP-ALL have a favorable prognosis. To get an insight in the underlying biology, we compared gene expression between NUTM1-positive and NUTM1-negative pediatric B-other cases. We identified 130 differentially expressed probe sets (FDR ≤0.01) with a peculiar enrichment of those located on chromosome band 10p12.31 (Bonferroni adjusted p=4.05E-04). The genes in cytoband 10p12.31, including BMI1, were variably upregulated in 6/7 NUTM1-positive cases and positively correlated to NUTM1 expression levels. The NUTM1 protein is capable of binding and hereby stimulating the histone acetyltransferase activity of the EP300 protein. The EP300 protein preferentially binds a risk allele of BMI1 associated with increased risk for BCP-ALL. The BMI1 protein has been shown to convert BCR-ABL1-positive progenitor cells into BCR-ABL1-positive BCP-ALL cells. Hence, we postulate that NUTM1 fusion proteins contribute to leukemogenesis by stimulating EP300, leading to upregulation of BMI1 and other 10p12.31 genes in BCP-ALL. CONCLUSION NUTM1 fusions are a rare but recurrent event in BCP-ALL that seems to have a good prognosis. The NUTM1 fusions result in expression of the normally silent NUTM1 gene and are associated with upregulation of a cluster of genes on 10p12.31 including the leukemogenic BMI1 gene. Disclosures No relevant conflicts of interest to declare.

scholarly journals RNA Sequencing revealed differentially expressed genes functionally associated with immunity and tumor suppression during latent phase infection of a vv + MDV in chickens

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Kunzhe Dong ◽  
Shuang Chang ◽  
Qingmei Xie ◽  
Peng Zhao ◽  
Huanmin Zhang
Keyword(s):  
Gene Expression ◽  
Rna Sequencing ◽  
Differentially Expressed Genes ◽  
Host Defense ◽  
Tumor Suppression ◽  
Genetic Resistance ◽  
Early Mortality ◽  
Differentially Expressed ◽  
Sequencing Analysis ◽  
Latent Phase

Abstract Very virulent plus Marek’s disease (MD) virus (vv + MDV) induces tumors in relatively resistant lines of chickens and early mortality in highly susceptible lines of chickens. The vv + MDV also triggers a series of cellular responses in both types of chickens. We challenged birds sampled from a highly inbred chicken line (line 63) that is relatively resistant to MD and from another inbred line (line 72) that is highly susceptible to MD with a vv + MDV. RNA-sequencing analysis was performed with samples extracted from spleen tissues taken at 10-day and 21-day post infection (dpi). A total of 64 and 106 differentially expressed genes was identified in response to the vv + MDV challenge at latent phase in the resistant and susceptible lines of chickens, respectively. Direct comparisons between samples of the two lines identified 90 and 126 differentially expressed genes for control and MDV challenged groups, respectively. The differentially expressed gene profiles illustrated that intensive defense responses were significantly induced by vv + MDV at 10 dpi and 21 dpi but with slight changes in the resistant line. In contrast, vv + MDV induced a measurable suppression of gene expression associated with host defense at 10 dpi but followed by an apparent activation of the defense response at 21 dpi in the susceptible line of chickens. The observed difference in gene expression between the two genetic lines of chickens in response to MDV challenge during the latent phase provided a piece of indirect evidence that time points for MDV reactivation differ between the genetic lines of chickens with different levels of genetic resistance to MD. Early MDV reactivation might be necessary and potent to host defense system readiness for damage control of tumorigenesis and disease progression, which consequently results in measurable differences in phenotypic characteristics including early mortality (8 to 20 dpi) and tumor incidence between the resistant and susceptible lines of chickens. Combining differential gene expression patterns with reported GO function terms and quantitative trait loci, a total of 27 top genes was selected as highly promising candidate genes for genetic resistance to MD. These genes are functionally involved with virus process (F13A1 and HSP90AB1), immunity (ABCB1LB, RGS5, C10ORF58, OSF-2, MMP7, CXCL12, GAL1, GAL2, GAL7, HVCN1, PDE4D, IL4I1, PARP9, EOMES, MPEG1, PDK4, CCLI10, K60 and FST), and tumor suppression (ADAMTS2, LXN, ARRDC3, WNT7A, CLDN1 and HPGD). It is anticipated that these findings will facilitate advancement in the fundamental understanding on mechanisms of genetic resistance to MD. In addition, such advancement may also provide insights on tumor virus-induced tumorigenesis in general and help the research community recognize MD study may serve as a good model for oncology study involving tumor viruses.

scholarly journals Transcriptome Analysis of Orbital Adipose Tissue in Active Thyroid Eye Disease Using Next Generation RNA Sequencing Technology

2018 ◽  
Vol 12 (1) ◽  
pp. 41-52 ◽  
Author(s):  
Bradford W. Lee ◽  
Virender B. Kumar ◽  
Pooja Biswas ◽  
Audrey C. Ko ◽  
Ramzi M. Alameddine ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Differential Expression ◽  
Rna Sequencing ◽  
Differentially Expressed Genes ◽  
Thyroid Eye Disease ◽  
Differentially Expressed ◽  
Eye Disease ◽  
Healthy Controls ◽  
Rna Seq ◽  
Next Generation

Objective: This study utilized Next Generation Sequencing (NGS) to identify differentially expressed transcripts in orbital adipose tissue from patients with active Thyroid Eye Disease (TED) versus healthy controls. Method: This prospective, case-control study enrolled three patients with severe, active thyroid eye disease undergoing orbital decompression, and three healthy controls undergoing routine eyelid surgery with removal of orbital fat. RNA Sequencing (RNA-Seq) was performed on freshly obtained orbital adipose tissue from study patients to analyze the transcriptome. Bioinformatics analysis was performed to determine pathways and processes enriched for the differential expression profile. Quantitative Reverse Transcriptase-Polymerase Chain Reaction (qRT-PCR) was performed to validate the differential expression of selected genes identified by RNA-Seq. Results: RNA-Seq identified 328 differentially expressed genes associated with active thyroid eye disease, many of which were responsible for mediating inflammation, cytokine signaling, adipogenesis, IGF-1 signaling, and glycosaminoglycan binding. The IL-5 and chemokine signaling pathways were highly enriched, and very-low-density-lipoprotein receptor activity and statin medications were implicated as having a potential role in TED. Conclusion: This study is the first to use RNA-Seq technology to elucidate differential gene expression associated with active, severe TED. This study suggests a transcriptional basis for the role of statins in modulating differentially expressed genes that mediate the pathogenesis of thyroid eye disease. Furthermore, the identification of genes with altered levels of expression in active, severe TED may inform the molecular pathways central to this clinical phenotype and guide the development of novel therapeutic agents.

Analysis of Differentially Expressed Genes in Prunus persica for the Treatment of Hypoxia Using Generalized Linear Models

2020 ◽  
Vol 17 (9) ◽  
pp. 4183-4189
Author(s):  
Nisha Baid ◽  
Preethi Meghadri ◽  
Vinai G. Biju ◽  
Blessy B. Mathew ◽  
C. M. Prashanth
Keyword(s):  
Gene Expression ◽  
Rna Sequencing ◽  
Differentially Expressed Genes ◽  
Generalized Linear Models ◽  
Prunus Persica ◽  
Linear Models ◽  
Expression Patterns ◽  
High Capacity ◽  
Differentially Expressed ◽  
Root Tissues

The gene structure of organisms gets altered when exposed to an abnormal condition which could adversely affect the growth of the target. RNA sequencing can be deployed to identify diseasecausing mutations in the genes of patients for whom genetic analysis failed to return a diagnosis. One such disease is Hypoxia, a condition in which there is a deficiency in the availability of oxygen in the tissues. RNA sequencing helps in analyzing the global expression patterns of hypoxia and in understanding the cellular alterations of those suffering from it. It gives an understanding of the comprehensive regulation of the gene expression by environmental spur or specific factors which can be used to diagnose and treat hypoxia before it gets fatal. Prunus persica is a plant which has a high capacity for anoxic tolerance, and analyzing the gene expression changes which are associated to hypoxia treatments in the root tissues of two genotypes of the peach plant (Flooding tolerant and Flooding sensitive) can prevent physiological disorders. Further, gene ontology is used to cover three domains-cellular component, molecular function and biological processes related to the differentially expressed genes. We use Generalized Linear Models here, to find the differentially expressed genes in Prunus persica when exposed to the conditions of Hypoxia (Absence of Oxygen) and Normoxia (Excess of Oxygen) and find their Ontologies and genomic pathways to understand and diagnose the Processes that are most affected.

scholarly journals Identification of hypoxia-specific biomarkers in salmonids using RNA-sequencing and validation using high-throughput qPCR

2020 ◽  
Author(s):  
Arash Akbarzadeh ◽  
Aimee Lee S. Houde ◽  
Ben J.G. Sutherland ◽  
Oliver P. Günther ◽  
Kristina M. Miller
Keyword(s):  
Gene Expression ◽  
Dissolved Oxygen ◽  
Rna Sequencing ◽  
Differentially Expressed Genes ◽  
Chinook Salmon ◽  
Differentially Expressed ◽  
Early Gene ◽  
Hypoxic Stress ◽  
Rna Seq ◽  
Anthropogenic Habitat

AbstractIdentifying early gene expression responses to hypoxia (i.e., low dissolved oxygen) as a tool to assess the degree of exposure to this stressor is crucial for salmonids, because they are increasingly exposed to hypoxic stress due to anthropogenic habitat change, e.g., global warming, excessive nutrient loading, and persistent algal blooms. Our goal was to discover and validate gill gene expression biomarkers specific to the hypoxia response in salmonids across multi-stressor conditions. Gill tissue was collected from 24 freshwater juvenile Chinook salmon (Oncorhynchus tshawytscha), held in normoxia [dissolved oxygen (DO) > 8 mg L−1] and hypoxia (DO = 4□5 mg L−1) in 10 and 18°C temperatures for up to six days. RNA-sequencing (RNA-seq) was then used to discover 240 differentially expressed genes between hypoxic and normoxic conditions, but not affected by temperature. The most significantly differentially expressed genes had functional roles in the cell cycle and suppression of cell proliferation associated with hypoxic conditions. The most significant genes (n = 30) were selected for real-time qPCR assay development. These assays demonstrated a strong correlation (r = 0.88; p < 0.001) between the expression values from RNA-seq and the fold changes from qPCR. Further, qPCR of the 30 candidate hypoxia biomarkers was applied to an additional 322 Chinook salmon exposed to hypoxic and normoxic conditions to reveal the top biomarkers to define hypoxic stress. Multivariate analyses revealed that smolt stage, water salinity, and morbidity status were relevant factors to consider with the expression of these genes in relation to hypoxic stress. These hypoxia candidate genes will be put into application screening Chinook salmon to determine the identity of stressors impacting the fish.

scholarly journals ViDGER: An R package for integrative interpretation of differential gene expression results of RNA-seq data

2018 ◽  
Author(s):  
Adam McDermaid ◽  
Brandon Monier ◽  
Jing Zhao ◽  
Qin Ma
Keyword(s):  
Gene Expression ◽  
Rna Sequencing ◽  
Differential Gene Expression ◽  
Differentially Expressed Genes ◽  
R Package ◽  
Differentially Expressed ◽  
Rna Seq ◽  
Differential Gene

AbstractDifferential gene expression (DGE) is one of the most common applications of RNA-sequencing (RNA-seq) data. This process allows for the elucidation of differentially expressed genes (DEGs) across two or more conditions. Interpretation of the DGE results can be non-intuitive and time consuming due to the variety of formats based on the tool of choice and the numerous pieces of information provided in these results files. Here we present an R package, ViDGER (Visualization of Differential Gene Expression Results using R), which contains nine functions that generate information-rich visualizations for the interpretation of DGE results from three widely-used tools, Cuffdiff, DESeq2, and edgeR.

scholarly journals Identification of Hypoxia-Specific Biomarkers in Salmonids Using RNA-Sequencing and Validation Using High-Throughput qPCR

2020 ◽  
Vol 10 (9) ◽  
pp. 3321-3336
Author(s):  
Arash Akbarzadeh ◽  
Aimee Lee S Houde ◽  
Ben J G Sutherland ◽  
Oliver P Günther ◽  
Kristina M Miller
Keyword(s):  
Gene Expression ◽  
Dissolved Oxygen ◽  
Rna Sequencing ◽  
Differentially Expressed Genes ◽  
Chinook Salmon ◽  
Differentially Expressed ◽  
Early Gene ◽  
Hypoxic Stress ◽  
Rna Seq ◽  
Anthropogenic Habitat

Abstract Identifying early gene expression responses to hypoxia (i.e., low dissolved oxygen) as a tool to assess the degree of exposure to this stressor is crucial for salmonids, because they are increasingly exposed to hypoxic stress due to anthropogenic habitat change, e.g., global warming, excessive nutrient loading, and persistent algal blooms. Our goal was to discover and validate gill gene expression biomarkers specific to the hypoxia response in salmonids across multi-stressor conditions. Gill tissue was collected from 24 freshwater juvenile Chinook salmon (Oncorhynchus tshawytscha), held in normoxia [dissolved oxygen (DO) &gt; 8 mg L-1] and hypoxia (DO = 4‒5 mg L-1) in 10 and 18° temperatures for up to six days. RNA-sequencing (RNA-seq) was then used to discover 240 differentially expressed genes between hypoxic and normoxic conditions, but not affected by temperature. The most significantly differentially expressed genes had functional roles in the cell cycle and suppression of cell proliferation associated with hypoxic conditions. The most significant genes (n = 30) were selected for real-time qPCR assay development. These assays demonstrated a strong correlation (r = 0.88; P &lt; 0.001) between the expression values from RNA-seq and the fold changes from qPCR. Further, qPCR of the 30 candidate hypoxia biomarkers was applied to an additional 322 Chinook salmon exposed to hypoxic and normoxic conditions to reveal the top biomarkers to define hypoxic stress. Multivariate analyses revealed that smolt stage, water salinity, and morbidity status were relevant factors to consider with the expression of these genes in relation to hypoxic stress. These hypoxia candidate genes will be put into application screening Chinook salmon to determine the identity of stressors impacting the fish.

scholarly journals Aligning the Aligners: Comparison of RNA Sequencing Data Alignment and Gene Expression Quantification Tools for Clinical Breast Cancer Research

2019 ◽  
Vol 9 (2) ◽  
pp. 18 ◽  
Author(s):  
Isaac D. Raplee ◽  
Alexei V. Evsikov ◽  
Caralina Marín de Evsikova
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Research ◽  
Rna Sequencing ◽  
Differentially Expressed Genes ◽  
Ductal Carcinoma ◽  
Differentially Expressed ◽  
Rna Seq ◽  
Bioinformatics Tools ◽  
Ffpe Samples

The rapid expansion of transcriptomics and affordability of next-generation sequencing (NGS) technologies generate rocketing amounts of gene expression data across biology and medicine, including cancer research. Concomitantly, many bioinformatics tools were developed to streamline gene expression and quantification. We tested the concordance of NGS RNA sequencing (RNA-seq) analysis outcomes between two predominant programs for read alignment, HISAT2, and STAR, and two most popular programs for quantifying gene expression in NGS experiments, edgeR and DESeq2, using RNA-seq data from breast cancer progression series, which include histologically confirmed normal, early neoplasia, ductal carcinoma in situ and infiltrating ductal carcinoma samples microdissected from formalin fixed, paraffin embedded (FFPE) breast tissue blocks. We identified significant differences in aligners’ performance: HISAT2 was prone to misalign reads to retrogene genomic loci, STAR generated more precise alignments, especially for early neoplasia samples. edgeR and DESeq2 produced similar lists of differentially expressed genes, with edgeR producing more conservative, though shorter, lists of genes. Gene Ontology (GO) enrichment analysis revealed no skewness in significant GO terms identified among differentially expressed genes by edgeR versus DESeq2. As transcriptomics of FFPE samples becomes a vanguard of precision medicine, choice of bioinformatics tools becomes critical for clinical research. Our results indicate that STAR and edgeR are well-suited tools for differential gene expression analysis from FFPE samples.

scholarly journals Differentially expressed genes for atrial fibrillation identified by RNA sequencing from paired human left and right atrial appendages

2019 ◽  
Vol 51 (8) ◽  
pp. 323-332 ◽  
Author(s):  
Alison M. Thomas ◽  
Claudia P. Cabrera ◽  
Malcolm Finlay ◽  
Kulvinder Lall ◽  
Muriel Nobles ◽  
...  
Keyword(s):  
Gene Expression ◽  
Atrial Fibrillation ◽  
Sinus Rhythm ◽  
Rna Sequencing ◽  
Differential Gene Expression ◽  
Differentially Expressed Genes ◽  
Differentially Expressed ◽  
Right Atrial ◽  
Differential Gene ◽  
Left And Right

Atrial fibrillation is a significant worldwide contributor to cardiovascular morbidity and mortality. Few studies have investigated the differences in gene expression between the left and right atrial appendages, leaving their characterization largely unexplored. In this study, differential gene expression was investigated in atrial fibrillation and sinus rhythm using left and right atrial appendages from the same patients. RNA sequencing was performed on the left and right atrial appendages from five sinus rhythm (SR) control patients and five permanent AF case patients. Differential gene expression in both the left and right atrial appendages was analyzed using the Bioconductor package edgeR. A selection of differentially expressed genes, with relevance to atrial fibrillation, were further validated using quantitative RT-PCR. The distribution of the samples assessed through principal component analysis showed distinct grouping between left and right atrial appendages and between SR controls and AF cases. Overall 157 differentially expressed genes were identified to be downregulated and 90 genes upregulated in AF. Pathway enrichment analysis indicated a greater involvement of left atrial genes in the Wnt signaling pathway whereas right atrial genes were involved in clathrin-coated vesicle and collagen formation. The differing expression of genes in both left and right atrial appendages indicate that there are different mechanisms for development, support and remodeling of AF within the left and right atria.

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