scholarly journals Characterizing the Cancer-Associated Microbiome with Small RNA Sequencing Data

2019 ◽  
Author(s):  
Wei-Hao Lee ◽  
Kai-Pu Chen ◽  
Kai Wang ◽  
Hsuan-Cheng Huang ◽  
Hsueh-Fen Juan
Keyword(s):  
Small Rna ◽  
The Cancer Genome Atlas ◽  
Small Rna Sequencing ◽  
Sequencing Data ◽  
Microbial Composition ◽  
Rna Sequences ◽  
Colon And Rectal Cancer ◽  
Microrna Sequencing ◽  
Cancer Genome Atlas ◽  
Inflammatory Immune Response

AbstractThe microbiome is recognized as a quasi-organ in the human body. In particular, the gut microbiome is correlated with immune function, metabolism, and tumorigenesis. When dysbiosis of the microbiome occurs, this variation may contribute to alterations in the microenvironment, potentially inducing an inflammatory immune response and providing a niche for neoplastic growth. However, there is limited evidence regarding the correlation and interaction between the microbiome and tumorigenesis. By utilizing microRNA sequencing data of patients with colon and rectal cancer from The Cancer Genome Atlas, we designed a novel analytical process to extract non-human small RNA sequences and align them with the microbial genome to obtain a comprehensive view of the cancer-associated microbiome. In the present study, we identified > 1000 genera among 630 colorectal samples and clustered these samples into three distinctive colorectal enterotypes. Each cluster has its own distinctive microbial composition and interactions. Furthermore, we found 12 genera from these clusters that are associated with cancer stages and revealed their putative functions. Our results indicate that the proposed analytical approach can effectively determine the cancer-associated microbiome. It may be readily applied to explore other types of cancer, in which specimens of the microbiome are difficult to collect.

scholarly journals DBtRend: A Web-Server of tRNA Expression Profiles from Small RNA Sequencing Data in Humans

Genes ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 1576
Author(s):  
Jin-Ok Lee ◽  
Minho Lee ◽  
Yeun-Jun Chung
Keyword(s):  
Small Rna ◽  
Molecular Subtype ◽  
Expression Profiles ◽  
Web Server ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Small Rna Sequencing ◽  
Sequencing Data ◽  
Microrna Sequencing ◽  
User Friendly

Transfer RNA (tRNA), a key component of the translation machinery, plays critical roles in stress conditions and various diseases. While knowledge regarding the importance of tRNA function is increasing, its biological roles are still not well understood. There is currently no comprehensive database or web server providing the expression landscape of tRNAs across a variety of human tissues and diseases. Here, we constructed a user-friendly and interactive database, DBtRend, which provides a profile of mature tRNA expression across various biological conditions by reanalyzing the small RNA or microRNA sequencing data from the Cancer Genome Atlas (TCGA) and NCBI’s Gene Expression Omnibus (GEO) in humans. Users can explore not only the expression values of mature individual tRNAs in the human genome, but also those of isodecoders and isoacceptors based on our specific pipelines. DBtRend provides the expressed patterns of tRNAs, the differentially expressed tRNAs in different biological conditions, and the information of samples or patients, tissue types, and molecular subtype of cancers. The database is expected to help researchers interested in functional discoveries of tRNAs.

scholarly journals Upgrading the Repertoire of miRNAs in Gastric Adenocarcinoma to Provide a New Resource for Biomarker Discovery

2019 ◽  
Vol 20 (22) ◽  
pp. 5697 ◽  
Author(s):  
Michelle E. Pewarchuk ◽  
Mateus C. Barros-Filho ◽  
Brenda C. Minatel ◽  
David E. Cohn ◽  
Florian Guisier ◽  
...  
Keyword(s):  
Gastric Adenocarcinoma ◽  
Biomarker Discovery ◽  
The Cancer Genome Atlas ◽  
Small Rna Sequencing ◽  
Sequencing Data ◽  
Specific Expression ◽  
Novel Mirna ◽  
Cancer Genome Atlas ◽  
Context Specific ◽  
Independent Cohort

Recent studies have uncovered microRNAs (miRNAs) that have been overlooked in early genomic explorations, which show remarkable tissue- and context-specific expression. Here, we aim to identify and characterize previously unannotated miRNAs expressed in gastric adenocarcinoma (GA). Raw small RNA-sequencing data were analyzed using the miRMaster platform to predict and quantify previously unannotated miRNAs. A discovery cohort of 475 gastric samples (434 GA and 41 adjacent nonmalignant samples), collected by The Cancer Genome Atlas (TCGA), were evaluated. Candidate miRNAs were similarly assessed in an independent cohort of 25 gastric samples. We discovered 170 previously unannotated miRNA candidates expressed in gastric tissues. The expression of these novel miRNAs was highly specific to the gastric samples, 143 of which were significantly deregulated between tumor and nonmalignant contexts (p-adjusted < 0.05; fold change > 1.5). Multivariate survival analyses showed that the combined expression of one previously annotated miRNA and two novel miRNA candidates was significantly predictive of patient outcome. Further, the expression of these three miRNAs was able to stratify patients into three distinct prognostic groups (p = 0.00003). These novel miRNAs were also present in the independent cohort (43 sequences detected in both cohorts). Our findings uncover novel miRNA transcripts in gastric tissues that may have implications in the biology and management of gastric adenocarcinoma.

scholarly journals DEUS: an R package for accurate small RNA profiling based on differential expression of unique sequences

2019 ◽  
Vol 35 (22) ◽  
pp. 4834-4836
Author(s):  
Tim Jeske ◽  
Peter Huypens ◽  
Laura Stirm ◽  
Selina Höckele ◽  
Christine M Wurmser ◽  
...  
Keyword(s):  
Differential Expression ◽  
Small Rna ◽  
Sequence Similarity ◽  
Differential Expression Analysis ◽  
R Package ◽  
Supplementary Information ◽  
Small Rna Sequencing ◽  
Sequencing Data ◽  
Rna Sequences ◽  
Rna Profiling

Abstract Summary Despite their fundamental role in various biological processes, the analysis of small RNA sequencing data remains a challenging task. Major obstacles arise when short RNA sequences map to multiple locations in the genome, align to regions that are not annotated or underwent post-transcriptional changes which hamper accurate mapping. In order to tackle these issues, we present a novel profiling strategy that circumvents the need for read mapping to a reference genome by utilizing the actual read sequences to determine expression intensities. After differential expression analysis of individual sequence counts, significant sequences are annotated against user defined feature databases and clustered by sequence similarity. This strategy enables a more comprehensive and concise representation of small RNA populations without any data loss or data distortion. Availability and implementation Code and documentation of our R package at http://ibis.helmholtz-muenchen.de/deus/. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals Extensive Analysis of miRNA Trimming and Tailing Indicates that AGO1 Has a Complex Role in miRNA Turnover

Plants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 267
Author(s):  
Axel J. Giudicatti ◽  
Ariel H. Tomassi ◽  
Pablo A. Manavella ◽  
Agustin L. Arce
Keyword(s):  
Small Rna ◽  
Stress Responses ◽  
Cellular Localization ◽  
Mirna Biogenesis ◽  
Small Rna Sequencing ◽  
Sequencing Data ◽  
Extensive Analysis ◽  
Small Regulatory Rnas ◽  
Regulatory Rnas ◽  
Argonaute 1

MicroRNAs are small regulatory RNAs involved in several processes in plants ranging from development and stress responses to defense against pathogens. In order to accomplish their molecular functions, miRNAs are methylated and loaded into one ARGONAUTE (AGO) protein, commonly known as AGO1, to stabilize and protect the molecule and to assemble a functional RNA-induced silencing complex (RISC). A specific machinery controls miRNA turnover to ensure the silencing release of targeted-genes in given circumstances. The trimming and tailing of miRNAs are fundamental modifications related to their turnover and, hence, to their action. In order to gain a better understanding of these modifications, we analyzed Arabidopsis thaliana small RNA sequencing data from a diversity of mutants, related to miRNA biogenesis, action, and turnover, and from different cellular fractions and immunoprecipitations. Besides confirming the effects of known players in these pathways, we found increased trimming and tailing in miRNA biogenesis mutants. More importantly, our analysis allowed us to reveal the importance of ARGONAUTE 1 (AGO1) loading, slicing activity, and cellular localization in trimming and tailing of miRNAs.

scholarly journals Heme Biosynthesis mRNA Expression Signature: Towards a Novel Prognostic Biomarker in Patients with Diffusely Infiltrating Gliomas

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 662
Author(s):  
Mario Mischkulnig ◽  
Barbara Kiesel ◽  
Daniela Lötsch ◽  
Thomas Roetzer ◽  
Martin Borkovec ◽  
...  
Keyword(s):  
Overall Survival ◽  
Mrna Expression ◽  
Postoperative Management ◽  
Heme Biosynthesis ◽  
The Cancer Genome Atlas ◽  
Sequencing Data ◽  
Who Grade ◽  
Expression Signature ◽  
Cancer Genome Atlas ◽  
The Impact

Diffusely infiltrating gliomas are characterized by a variable clinical course, and thus novel prognostic biomarkers are needed. The heme biosynthesis cycle constitutes a fundamental metabolic pathway and might play a crucial role in glioma biology. The aim of this study was thus to investigate the role of the heme biosynthesis mRNA expression signature on prognosis in a large glioma patient cohort. Glioma patients with available sequencing data on heme biosynthesis expression were retrieved from The Cancer Genome Atlas (TCGA). In each patient, the heme biosynthesis mRNA expression signature was calculated and categorized into low, medium, and high expression subgroups. Differences in progression-free and overall survival between these subgroups were investigated including a multivariate analysis correcting for WHO grade, tumor subtype, and patient age and sex. In a total of 693 patients, progression-free and overall survival showed a strictly monotonical decrease with increasing mRNA expression signature subgroups. In detail, median overall survival was 134.2 months in the low, 79.9 months in the intermediate, and 16.5 months in the high mRNA expression signature subgroups, respectively. The impact of mRNA expression signature on progression-free and overall survival was independent of the other analyzed prognostic factors. Our data indicate that the heme biosynthesis mRNA expression signature might serve as an additional novel prognostic marker in patients with diffusely infiltrating gliomas to optimize postoperative management.

scholarly journals Effect of Different Expression of Immune-Related lncRNA on Colon Adenocarcinoma and Its Relation to Prognosis

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Meiwei Mu ◽  
Yi Tang ◽  
Zheng Yang ◽  
Yuling Qiu ◽  
Xiaohong Li ◽  
...  
Keyword(s):  
Cox Regression ◽  
Colon Adenocarcinoma ◽  
The Cancer Genome Atlas ◽  
Risk Scores ◽  
Future Research ◽  
Sequencing Data ◽  
Tissue Samples ◽  
Gene Sets ◽  
Cancer Genome Atlas ◽  
Immune Related Genes

Objective. To explore the expression of immune-related lncRNAs in colon adenocarcinoma and find out the effect on how these lncRNAs influence the development and prognosis of colon adenocarcinoma. Method. Transcriptome data of colon adenocarcinoma from The Cancer Genome Atlas (TCGA) were downloaded, and gene sets “IMMUNE RESPONSE” and “IMMUNE SYSTEM PROCESS” were sought from the Molecular Signatures Database (MSigDB). The expression of immune-related genes was extracted that were immune-related mRNAs. Then, the immune-related lncRNAs were sought out by utilizing of the above data. Clinical traits were combined with immune-related lncRNAs, so that prognostic-related lncRNAs were identified by Cox regression. Multivariate Cox regression was built to calculate risk scores. Relationships between clinical traits and immune-related lncRNAs were also calculated. Result. A total of 480 colorectal adenocarcinoma patients and 41 normal control patients’ transcriptome sequencing data of tissue samples were obtained from TCGA database. 918 immune-related lncRNAs were screened. Cox regression showed that 34 immune-related lncRNAs were associated with colon adenocarcinoma prognosis. Seven lncRNAs were independent risk factors. Conclusion. This study revealed that some lncRNAs can affect the development and prognosis of colon adenocarcinoma. It may provide new theory evidence of molecular mechanism for the future research and molecular targeted therapy of colon adenocarcinoma.

scholarly journals An R Package for Divergence Analysis of Omics Data

2019 ◽  
Author(s):  
Wikum Dinalankara ◽  
Qian Ke ◽  
Donald Geman ◽  
Luigi Marchionni
Keyword(s):  
High Throughput Sequencing ◽  
R Package ◽  
The Cancer Genome Atlas ◽  
High Dimensional ◽  
Omics Data ◽  
Sequencing Data ◽  
High Throughput Sequencing Data ◽  
Ternary Code ◽  
Cancer Genome Atlas ◽  
Level Analysis

AbstractGiven the ever-increasing amount of high-dimensional and complex omics data becoming available, it is increasingly important to discover simple but effective methods of analysis. Divergence analysis transforms each entry of a high-dimensional omics profile into a digitized (binary or ternary) code based on the deviation of the entry from a given baseline population. This is a novel framework that is significantly different from existing omics data analysis methods: it allows digitization of continuous omics data at the univariate or multivariate level, facilitates sample level analysis, and is applicable on many different omics platforms. The divergence package, available on the R platform through the Bioconductor repository collection, provides easy-to-use functions for carrying out this transformation. Here we demonstrate how to use the package with sample high throughput sequencing data from the Cancer Genome Atlas.

scholarly journals Somatic transposition in the Drosophila intestine occurs in active chromatin and is associated with tumor suppressor gene inactivation

2020 ◽  
Author(s):  
Katarzyna Siudeja ◽  
Marius van den Beek ◽  
Nick Riddiford ◽  
Benjamin Boumard ◽  
Annabelle Wurmser ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Small Rna ◽  
Suppressor Gene ◽  
Somatic Tissue ◽  
Small Rna Sequencing ◽  
Sequencing Data ◽  
Active Chromatin ◽  
Tumor Suppressor Gene Inactivation ◽  
Somatic Transposition

AbstractTransposable elements (TEs) play a significant role in evolution by contributing to genetic variation through germline insertional activity. However, how TEs act in somatic cells and tissues is not well understood. Here, we address the prevalence of transposition in a somatic tissue, exploiting the Drosophila midgut as a model system. Using whole-genome sequencing of in vivo clonally expanded gut tissue, we map hundreds of high-confidence somatic TE integration sites genome-wide. We show that somatic retrotransposon insertions are associated with inactivation of the tumor suppressor Notch, likely contributing to neoplasia formation. Moreover, by applying Oxford Nanopore long-read sequencing technology, as well as by mapping germline TE activity, we provide evidence suggesting tissue-specific differences in retrotransposition. By comparing somatic TE insertional activity with transcriptomic and small RNA sequencing data, we demonstrate that transposon mobility cannot be simply predicted by whole tissue TE expression levels or by small RNA pathway activity. Finally, we reveal that somatic TE insertions in the adult fly intestine are found preferentially in genic regions and open, transcriptionally active chromatin. Together, our findings provide clear evidence of ongoing somatic transposition in Drosophila and delineate previously unknown underlying features of somatic TE mobility in vivo.

scholarly journals Genomic Landscape of Early-stage Colorectal Neoplasia Developing From the Ulcerative Colitis Mucosa in the Japanese Population

2020 ◽  
Author(s):  
Kenta Matsumoto ◽  
Yuji Urabe ◽  
Shiro Oka ◽  
Katsuaki Inagaki ◽  
Hidenori Tanaka ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Early Stage ◽  
Colorectal Neoplasia ◽  
Genomic Analysis ◽  
The Cancer Genome Atlas ◽  
Sequencing Data ◽  
Kras Mutations ◽  
Tp53 Mutations ◽  
Amino Terminal ◽  
Cancer Genome Atlas

Abstract Backgrounds Colorectal neoplasias (CRN)s developing from the ulcerative colitis (UC) mucosa include both colitic and sporadic neoplasias. Although several genomic analyses of advanced colitis-associated cancer are available, such studies do not distinguish between colitic and sporadic cases, and the early-stage genomic alterations involved in the onset of colitic cancer remain unclear. To address this, we performed a genomic analysis of early-stage CRN developing from the UC mucosa (CRNUC). Methods We extracted DNA from 36 early-stage CRNUCs (T1 cancer, 10; dysplasia, 26) from 32 UC patients and performed targeted sequencing of 43 genes commonly associated with colitis-associated cancer and compared the results with sequencing data from the Japanese invasive colitis-associated cancer. Results The most frequently mutated gene in the CRNUC cohort was APC (mutated in 47.2% of the cases), followed by TP53 (44.4%), KRAS (27.8%), and PRKDC (27.8%). None of the TP53 mutations occurred at any of the hotspot codons. Although the TP53 mutations in The Cancer Genome Atlas of Colorectal Cancer were dispersed throughout the gene, those detected here in CRNUC cases were concentrated in the amino terminal part of the DNA-binding domain. Interestingly, the mutations in KRAS and TP53 were mutually exclusive in CRNUC, and CRNUCs with KRAS mutations had histologically serrated lesions in the gland duct. Mayo endoscopic subscore was higher in TP53-mutated CRNUCs and lower in KRAS-mutated CRNUCs. Conclusions Our findings suggest that early-stage CRNUC can be classified into 2 groups: those developing through the carcinogenic pathway via TP53 mutations and those developing through the carcinogenic pathway via KRAS mutations.

scholarly journals Transposable element expression in tumors is associated with immune infiltration and increased antigenicity

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Yu Kong ◽  
Christopher M. Rose ◽  
Ashley A. Cass ◽  
Alexander G. Williams ◽  
Martine Darwish ◽  
...  
Keyword(s):  
Dna Methylation ◽  
De Novo ◽  
Computational Method ◽  
The Cancer Genome Atlas ◽  
Potential Consequence ◽  
Sequencing Data ◽  
Antiviral Responses ◽  
Genome Wide ◽  
Cancer Genome Atlas ◽  
Demethylation Agent

AbstractProfound global loss of DNA methylation is a hallmark of many cancers. One potential consequence of this is the reactivation of transposable elements (TEs) which could stimulate the immune system via cell-intrinsic antiviral responses. Here, we develop REdiscoverTE, a computational method for quantifying genome-wide TE expression in RNA sequencing data. Using The Cancer Genome Atlas database, we observe increased expression of over 400 TE subfamilies, of which 262 appear to result from a proximal loss of DNA methylation. The most recurrent TEs are among the evolutionarily youngest in the genome, predominantly expressed from intergenic loci, and associated with antiviral or DNA damage responses. Treatment of glioblastoma cells with a demethylation agent results in both increased TE expression and de novo presentation of TE-derived peptides on MHC class I molecules. Therapeutic reactivation of tumor-specific TEs may synergize with immunotherapy by inducing inflammation and the display of potentially immunogenic neoantigens.

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