Dataset Information

TETyper: a bioinformatic pipeline for classifying variation and genetic contexts of transposable elements from short-read whole-genome sequencing data.

ABSTRACT: Much of the worldwide dissemination of antibiotic resistance has been driven by resistance gene associations with mobile genetic elements (MGEs), such as plasmids and transposons. Although increasing, our understanding of resistance spread remains relatively limited, as methods for tracking mobile resistance genes through multiple species, strains and plasmids are lacking. We have developed a bioinformatic pipeline for tracking variation within, and mobility of, specific transposable elements (TEs), such as transposons carrying antibiotic-resistance genes. TETyper takes short-read whole-genome sequencing data as input and identifies single-nucleotide mutations and deletions within the TE of interest, to enable tracking of specific sequence variants, as well as the surrounding genetic context(s), to enable identification of transposition events. A major advantage of TETyper over previous methods is that it does not require a genome reference. To investigate global dissemination of Klebsiella pneumoniae carbapenemase (KPC) and its associated transposon Tn4401, we applied TETyper to a collection of over 3000 publicly available Illumina datasets containing blaKPC. This revealed surprising diversity, with over 200?distinct flanking genetic contexts for Tn4401, indicating high levels of transposition. Integration of sample metadata revealed insights into associations between geographic locations, host species, Tn4401 sequence variants and flanking genetic contexts. To demonstrate the ability of TETyper to cope with high-copy-number TEs and to track specific short-term evolutionary changes, we also applied it to the insertion sequence IS26 within a defined K. pneumoniae outbreak. TETyper is implemented in python and is freely available at https://github.com/aesheppard/TETyper.

SUBMITTER: Sheppard AE

PROVIDER: S-EPMC6412039 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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TETyper: a bioinformatic pipeline for classifying variation and genetic contexts of transposable elements from short-read whole-genome sequencing data.

Sheppard Anna E AE Stoesser Nicole N German-Mesner Ian I Vegesana Kasi K Sarah Walker A A Crook Derrick W DW Mathers Amy J AJ

Microbial genomics 20181122 12

Much of the worldwide dissemination of antibiotic resistance has been driven by resistance gene associations with mobile genetic elements (MGEs), such as plasmids and transposons. Although increasing, our understanding of resistance spread remains relatively limited, as methods for tracking mobile resistance genes through multiple species, strains and plasmids are lacking. We have developed a bioinformatic pipeline for tracking variation within, and mobility of, specific transposable elements (T ...[more]

PMID: 30465646

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Project description:In the Drosophila germline, transposable elements (TEs) are silenced by PIWI-interacting RNA (piRNA) that originate from distinct genomic regions termed piRNA clusters and are processed by PIWI-subfamily Argonaute proteins. Here, we explore the variation in the ability to restrain an alien TE in different Drosophila strains. The I-element is a retrotransposon involved in the phenomenon of I-R hybrid dysgenesis in Drosophila melanogaster. Genomes of R strains do not contain active I-elements, but harbour remnants of ancestral I-related elements. The permissivity to I-element activity of R females, called reactivity, varies considerably in natural R populations, indicating the existence of a strong natural polymorphism in defense systems targeting transposons. To reveal the nature of such polymorphisms, we compared ovarian small RNAs between R strains with low and high reactivity and show that reactivity negatively correlates with the ancestral I-element-specific piRNA content. Analysis of piRNA clusters containing remnants of I-elements shows increased expression of the piRNA precursors and enrichment by the Heterochromatin Protein 1 homolog, Rhino, in weak R strains, which is in accordance with stronger piRNA expression by these regions. To explore the nature of the differences in piRNA production, we focused on two R strains, weak and strong, and showed that the efficiency of maternal inheritance of piRNAs as well as the I-element copy number are very similar in both strains. At the same time, germline and somatic uni-strand piRNA clusters generate more piRNAs in strains with low reactivity, suggesting the relationship between the efficiency of primary piRNA production and variable response to TE invasions. The strength of adaptive genome defense is likely driven by naturally occurring polymorphisms in the rapidly evolving piRNA pathway proteins. We hypothesize that hyper-efficient piRNA production is contributing to elimination of a telomeric retrotransposon HeT-A, which we have observed in one particular transposon-resistant R strain.

Project description:BackgroundFunctional regulatory regions in eukaryotic genomes are characterized by the disruption of nucleosomes leading to accessible chromatin. The modulation of chromatin accessibility is one of the key mediators of transcriptional regulation, and variation in chromatin accessibility across individuals has been linked to complex traits and disease susceptibility. While mechanisms responsible for chromatin variation across individuals have been investigated, the overwhelming majority of chromatin variation remains unexplained. Furthermore, the processes through which the variation of chromatin accessibility contributes to phenotypic diversity remain poorly understood.ResultsWe profiled chromatin accessibility in liver from seven strains of mice with phenotypic diversity in response to a high-fat/high-sucrose (HF/HS) diet and identified reproducible chromatin variation across the individuals. We found that sites of variable chromatin accessibility were more likely to coincide with particular classes of transposable elements (TEs) than sites with common chromatin signatures. Evolutionarily younger long interspersed nuclear elements (LINEs) are particularly likely to harbor variable chromatin sites. These younger LINEs are enriched for binding sites of immune-associated transcription factors, whereas older LINEs are enriched for liver-specific transcription factors. Genomic region enrichment analysis indicates that variable chromatin sites at TEs may function to regulate liver metabolic pathways. CRISPR-Cas9 deletion of a number of variable chromatin sites at TEs altered expression of nearby metabolic genes. Finally, we show that polymorphism of TEs and differential DNA methylation at TEs can both influence chromatin variation.ConclusionsOur results demonstrate that specific classes of TEs show variable chromatin accessibility across strains of mice that display phenotypic diversity in response to a HF/HS diet. These results indicate that chromatin variation at TEs is an important contributor to phenotypic variation among populations.

Project description:Next-generation sequencing technology is of great importance for many biological disciplines; however, due to technical and biological limitations, the short DNA sequences produced by modern sequencers require numerous quality control (QC) measures to reduce errors, remove technical contaminants, or merge paired-end reads together into longer or higher-quality contigs. Many tools for each step exist, but choosing the appropriate methods and usage parameters can be challenging because the parameterization of each step depends on the particularities of the sequencing technology used, the type of samples being analyzed, and the stochasticity of the instrumentation and sample preparation. Furthermore, end users may not know all of the relevant information about how their data were generated, such as the expected overlap for paired-end sequences or type of adaptors used to make informed choices. This increasing complexity and nuance demand a pipeline that combines existing steps together in a user-friendly way and, when possible, learns reasonable quality parameters from the data automatically. We propose a user-friendly quality control pipeline called SHI7 (canonically pronounced "shizen"), which aims to simplify quality control of short-read data for the end user by predicting presence and/or type of common sequencing adaptors, what quality scores to trim, whether the data set is shotgun or amplicon sequencing, whether reads are paired end or single end, and whether pairs are stitchable, including the expected amount of pair overlap. We hope that SHI7 will make it easier for all researchers, expert and novice alike, to follow reasonable practices for short-read data quality control. IMPORTANCE Quality control of high-throughput DNA sequencing data is an important but sometimes laborious task requiring background knowledge of the sequencing protocol used (such as adaptor type, sequencing technology, insert size/stitchability, paired-endedness, etc.). Quality control protocols typically require applying this background knowledge to selecting and executing numerous quality control steps with the appropriate parameters, which is especially difficult when working with public data or data from collaborators who use different protocols. We have created a streamlined quality control pipeline intended to substantially simplify the process of DNA quality control from raw machine output files to actionable sequence data. In contrast to other methods, our proposed pipeline is easy to install and use and attempts to learn the necessary parameters from the data automatically with a single command.

Dataset Information

TETyper: a bioinformatic pipeline for classifying variation and genetic contexts of transposable elements from short-read whole-genome sequencing data.

Publications

TETyper: a bioinformatic pipeline for classifying variation and genetic contexts of transposable elements from short-read whole-genome sequencing data.

Similar Datasets

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