scholarly journals GeneTEFlow: A Nextflow-based pipeline for analysing gene and transposable elements expression from RNA-Seq data

2020 ◽  
Author(s):  
Xiaochuan Liu ◽  
Jadwiga R Bienkowska ◽  
Wenyan Zhong
Keyword(s):  
Transposable Elements ◽  
Expression Analysis ◽  
Comprehensive Analysis ◽  
Integrated Analysis ◽  
Computational Pipeline ◽  
Immune Functions ◽  
Rna Seq ◽  
One Stop ◽  
Eukaryotic Genomes

AbstractTransposable elements (TEs) are mobile genetic elements in eukaryotic genomes. Recent research highlights the important role of TEs in the embryogenesis, neurodevelopment, and immune functions. However, there is a lack of a one-stop and easy to use computational pipeline for expression analysis of both genes and locus-specific TEs from RNA-Seq data. Here, we present GeneTEFlow, a fully automated, reproducible and platform-independent workflow, for the comprehensive analysis of gene and locus-specific TEs expression from RNA-Seq data employing Nextflow and Docker technologies. This application will help researchers more easily perform integrated analysis of both gene and TEs expression, leading to a better understanding of roles of gene and TEs regulation in human diseases. GeneTEFlow is freely available at https://github.com/zhongw2/GeneTEFlow.

scholarly journals A Multi-Omics Study of Chicken Infected by Nephropathogenic Infectious Bronchitis Virus

Viruses ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1070 ◽  
Author(s):  
Puzhi Xu ◽  
Ping Liu ◽  
Changming Zhou ◽  
Yan Shi ◽  
Qingpeng Wu ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Infectious Bronchitis Virus ◽  
Metabolic Pathways ◽  
Host Responses ◽  
Integrated Analysis ◽  
Specific Gene ◽  
Rna Seq ◽  
Infectious Bronchitis ◽  
Infection Processes

Chicken gout resulting from nephropathogenic infectious bronchitis virus (NIBV) has become a serious kidney disease problem in chicken worldwide with alterations of the metabolic phenotypes in multiple metabolic pathways. To investigate the mechanisms in chicken responding to NIBV infection, we examined the global transcriptomic and metabolomic profiles of the chicken’s kidney using RNA-seq and GC–TOF/MS, respectively. Furthermore, we analyzed the alterations in cecal microorganism composition in chickens using 16S rRNA-seq. Integrated analysis of these three phenotypic datasets further managed to create correlations between the altered kidney transcriptomes and metabolome, and between kidney metabolome and gut microbiome. We found that 2868 genes and 160 metabolites were deferentially expressed or accumulated in the kidney during NIBV infection processes. These genes and metabolites were linked to NIBV-infection related processes, including immune response, signal transduction, peroxisome, purine, and amino acid metabolism. In addition, the comprehensive correlations between the kidney metabolome and cecal microbial community showed contributions of gut microbiota in the progression of NIBV-infection. Taken together, our research comprehensively describes the host responses during NIBV infection and provides new clues for further dissection of specific gene functions, metabolite affections, and the role of gut microbiota during chicken gout.

scholarly journals intePareto: an R package for integrative analyses of RNA-Seq and ChIP-Seq data

BMC Genomics ◽  
2020 ◽  
Vol 21 (S11) ◽  
Author(s):  
Yingying Cao ◽  
Simo Kitanovski ◽  
Daniel Hoffmann
Keyword(s):  
Gene Expression ◽  
Expression Analysis ◽  
High Throughput Sequencing ◽  
Differential Expression Analysis ◽  
Cell Types ◽  
R Package ◽  
Integrative Approach ◽  
Integrated Analysis ◽  
Data Sets ◽  
Rna Seq

Abstract Background RNA-Seq, the high-throughput sequencing (HT-Seq) of mRNAs, has become an essential tool for characterizing gene expression differences between different cell types and conditions. Gene expression is regulated by several mechanisms, including epigenetically by post-translational histone modifications which can be assessed by ChIP-Seq (Chromatin Immuno-Precipitation Sequencing). As more and more biological samples are analyzed by the combination of ChIP-Seq and RNA-Seq, the integrated analysis of the corresponding data sets becomes, theoretically, a unique option to study gene regulation. However, technically such analyses are still in their infancy. Results Here we introduce intePareto, a computational tool for the integrative analysis of RNA-Seq and ChIP-Seq data. With intePareto we match RNA-Seq and ChIP-Seq data at the level of genes, perform differential expression analysis between biological conditions, and prioritize genes with consistent changes in RNA-Seq and ChIP-Seq data using Pareto optimization. Conclusion intePareto facilitates comprehensive understanding of high dimensional transcriptomic and epigenomic data. Its superiority to a naive differential gene expression analysis with RNA-Seq and available integrative approach is demonstrated by analyzing a public dataset.

scholarly journals Integrated analysis reveals the alterations that LMNA interacts with euchromatin in LMNA mutation-associated dilated cardiomyopathy

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Xiaolin Zhang ◽  
Xiuli Shao ◽  
Ruijia Zhang ◽  
Rongli Zhu ◽  
Rui Feng
Keyword(s):  
Dilated Cardiomyopathy ◽  
Molecular Pathogenesis ◽  
Integrated Analysis ◽  
Rna Seq ◽  
Lmna Mutation ◽  
Differential Binding ◽  
Key Genes ◽  
Downstream Analysis ◽  
Pathological Disease

Abstract Background Dilated cardiomyopathy (DCM) is a serious cardiac heterogeneous pathological disease, which may be caused by mutations in the LMNA gene. Lamins interact with not only lamina-associated domains (LADs) but also euchromatin by alone or associates with the lamina-associated polypeptide 2 alpha (LAP2α). Numerous studies have documented that LMNA regulates gene expression by interacting with LADs in heterochromatin. However, the role of LMNA in regulating euchromatin in DCM is poorly understood. Here, we determine the differential binding genes on euchromatin in DCM induced by LMNA mutation by performing an integrated analysis of bioinformatics and explore the possible molecular pathogenesis mechanism. Results Six hundred twenty-three and 4484 differential binding genes were identified by ChIP-seq technology. The ChIP-seq analysis results and matched RNA-Seq transcriptome data were integrated to further validate the differential binding genes of ChIP-seq. Five and 60 candidate genes involved in a series of downstream analysis were identified. Finally, 4 key genes (CREBBP, PPP2R2B, BMP4, and BMP7) were harvested, and these genes may regulate LMNA mutation-induced DCM through WNT/β-catenin or TGFβ-BMP pathways. Conclusions We identified four key genes that may serve as potential biomarkers and novel therapeutic targets. Our study also illuminates the possible molecular pathogenesis mechanism that the abnormal binding between LMNA or LAP2α-lamin A/C complexes and euchromatin DNA in LMNA mutations, which may cause DCM through the changes of CREBBP, PPP2R2B, BMP4, BMP7 expressions, and the dysregulation of WNT/β-catenin or TGFβ-BMP pathways, providing valuable insights to improve the occurrence and development of DCM. Graphic abstract

scholarly journals N6-Methyladenosine Modification Regulates Cell Metabolism in Acute Myeloid Leukemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 880-880
Author(s):  
Hengyou Weng ◽  
Huilin Huang ◽  
Huizhe Wu ◽  
Mingli Sun ◽  
Savanna Stanford ◽  
...  
Keyword(s):  
Amino Acids ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Cell Metabolism ◽  
Conditional Knockout ◽  
Integrated Analysis ◽  
Rna Seq ◽  
Cell Immortalization ◽  
Acute Myeloid

Abstract As the most abundant internal RNA modification in eukaryotes, N6-methyladenosine (m6A) modification has been recently linked to various physiological and pathological processes, including tumorigenesis. m6A marks on mRNAs are mainly deposited by the METTL3/METTL14/WTAP methyltransferase ("writer") complex and could be removed by "eraser" proteins such as FTO or ALKBH5. We have shown recently that METTL14 (Weng H et al., Cell Stem Cell, 2018) and FTO (Li Z et al., Cancer Cell, 2017) both function as oncogenes in acute myeloid leukemia (AML), which together with the finding that METTL3 is also oncogenic in AML suggest that the m6A machinery plays critical roles in AML pathogenesis. Similar to other epigenetic modifications, the effect of m6A modification relies on effector proteins, the so-called m6A "reader" proteins. We recently identified a new class of m6A reader proteins, the IGF2BP protein family, which stabilize m6A-containing mRNAs and promote their translation through their K Homology (KH) domains (Huang H et al., Nature Cell Biology, 2018). Despite the well-studied oncogenic roles of IGF2BPs in solid cancer, little is known on the functions of IGF2BP proteins in leukemia. By analyzing expression of the IGF2BPs in AML using The Cancer Genome Atlas (TCGA) dataset, we found that one of the three IGF2BP genes, IGF2BP2, is highly expressed in AML compared to the vast majority of other types of cancer. Our qPCR assays also showed a significant elevated expression of IGF2BP2 in mononuclear cells from primary AML patients with various types of chromosome translocation (t(11q23), n=17, P<0.0001; t(15;17), n=5, P=0.0021; t(8;21), n=7, P<0.0001; inv(16), n=6, P<0.0001) compared to those from healthy donors (n=15). Knockdown of IGF2BP2 inhibits Mll-AF9-mediated colony forming in vitro (sh#1 vs. shCtrl, P=0.0113; sh#2 vs. shCtrl, P=0.0136), whereas overexpression of wild-type IGF2BP2 (wt vs. vehicle, P=0.0025), but not the inactive KH3-4-mutated form (mut vs. vehicle, P=0.3178), promotes cell immortalization. In addition, IGF2BP2-promoted cell transforming ability of Mll-AF9 was largely abolished in the absence of Mettl14 in bone marrow cells from Mettl14 conditional knockout mice (IGF2BP2/Ctrl in the presence of Mettl14=1.90±0.15, P=0.0030; IGF2BP2/Ctrl in the absence of Mettl14=1.28±0.10, P=0.0323). Such data indicate that the effect of IGF2BP2 on promoting cell immortalization is m6A dependent. Moreover, depletion of Igf2bp2 delays in vivo leukemogenesis mediated by Mll-AF9 and greatly prolonged the survival of recipient mice (shCtrl, medium survival=81 days, n=7; shIgf2bp2, medium survival>200 days, n=7; P=0.0031). To better understand the molecular mechanism underlying the role of IGF2BP2 in AML, we performed RNA-seq in IGF2BP2 knockdown AML cells or control cells. Integrated analysis of the RNA-seq data with our previously published cross-linking immunoprecipitation (CLIP) data (GSE90639 and GSE21918) reveals that targets of IGF2BP2 are enriched in biosynthesis of amino acids (P=0.0079) and metabolic pathways (P=0.0160). Expression changes of selected target genes, such as MYC, PHGDH, and ASNS, were confirmed by qPCR and immunoblotting in IGF2BP2 knockdown cells, with similar pattern being observed in METTL3 or METTL14 depleted cells. PHGDH encodes the key metabolic enzyme that catalyzes the rate-limiting step of the serine (Ser) biosynthesis pathway, whereas ASNS encodes an enzyme that converts aspartate (Asp) and glutamine (Gln) to asparagine (ASN) and glutamate (Glu). Metabolic profiling reveals that the synthesis of selected amino acids, including Ser, Asn, and Glu, was decreased in IGF2BP2-depleted cells (P=0.0415 for Ser, P=0.0109 for Asn, P=0.0018 for Glu), similar to that in METTL3 (P=0.0433 for Ser, P=0.0155 for Asn, P=0.0005 for Glu) or METTL14 (P=0.0478 for Ser, P=0.0057 for Asn, P=0.0043 for Glu) depleted cells. As expected, shRNA-mediated knockdown of IGF2BP2 in AML cells resulted in a significant inhibition on the glycolytic rate (P=0.0029 for sh#1, P=0.0024 for sh#2) and cell growth (P<0.0001 for both shRNAs from Day 1 to Day 4). Collectively, our data demonstrate a critical role of IGF2BP2 in AML pathogenesis as an m6A reader and provide novel evidence on the involvement of the m6A machinery on regulation of cell metabolism, which may have therapeutic implications for AML. Disclosures No relevant conflicts of interest to declare.

scholarly journals Locus-specific analysis of Transposable Elements during the progression of ALS in the SOD1G93A mouse model

PLoS ONE ◽  
2021 ◽  
Vol 16 (10) ◽  
pp. e0258291
Author(s):  
Braulio Valdebenito-Maturana ◽  
Esteban Arancibia ◽  
Gonzalo Riadi ◽  
Juan Carlos Tapia ◽  
Mónica Carrasco
Keyword(s):  
Gene Expression ◽  
Mouse Model ◽  
Transposable Elements ◽  
Large Fraction ◽  
Specific Role ◽  
Rna Seq ◽  
Specific Analysis ◽  
A Genome ◽  
Gene Expression Studies

Transposable Elements (TEs) are ubiquitous genetic elements with the ability to move within a genome. TEs contribute to a large fraction of the repetitive elements of a genome, and because of their nature, they are not routinely analyzed in RNA-Seq gene expression studies. Amyotrophic Lateral Sclerosis (ALS) is a lethal neurodegenerative disease, and a well-accepted model for its study is the mouse harboring the human SOD1G93A mutant. In this model, landmark stages of the disease can be recapitulated at specific time points, making possible to understand changes in gene expression across time. While there are several works reporting TE activity in ALS models, they have not explored their activity through the disease progression. Moreover, they have done it at the expense of losing their locus of expression. Depending on their genomic location, TEs can regulate genes in cis and in trans, making locus-specific analysis of TEs of importance in order to understand their role in modulating gene expression. Particularly, the locus-specific role of TEs in ALS has not been fully elucidated. In this work, we analyzed publicly available RNA-Seq datasets of the SOD1G93A mouse model, to understand the locus-specific role of TEs. We show that TEs become up-regulated at the early stages of the disease, and via statistical associations, we speculate that they can regulate several genes, which in turn might be contributing to the genetic dysfunction observed in ALS.

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