30,732 research outputs found

    Protein and DNA sequence determinants of thermophilic adaptation

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    Prokaryotes living at extreme environmental temperatures exhibit pronounced signatures in the amino acid composition of their proteins and nucleotide compositions of their genomes reflective of adaptation to their thermal environments. However, despite significant efforts, the definitive answer of what are the genomic and proteomic compositional determinants of Optimal Growth Temperature of prokaryotic organisms remained elusive. Here the authors performed a comprehensive analysis of amino acid and nucleotide compositional signatures of thermophylic adaptation by exhaustively evaluating all combinations of amino acids and nucleotides as possible determinants of Optimal Growth Temperature for all prokaryotic organisms with fully sequences genomes.. The authors discovered that total concentration of seven amino acids in proteomes, IVYWREL, serves as a universal proteomic predictor of Optimal Growth Temperature in prokaryotes. Resolving the old-standing controversy the authors determined that the variation in nucleotide composition (increase of purine load, or A+G content with temperature) is largely a consequence of thermal adaptation of proteins. However, the frequency with which A and G nucleotides appear as nearest neighbors in genome sequences is strongly and independently correlated with Optimal Growth Temperature. as a result of codon bias in corresponding genomes. Together these results provide a complete picture of proteomic and genomic determinants of thermophilic adaptation.Comment: in press PLoS Computational Biology; revised versio

    SVIM: Structural Variant Identification using Mapped Long Reads

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    Motivation: Structural variants are defined as genomic variants larger than 50bp. They have been shown to affect more bases in any given genome than SNPs or small indels. Additionally, they have great impact on human phenotype and diversity and have been linked to numerous diseases. Due to their size and association with repeats, they are difficult to detect by shotgun sequencing, especially when based on short reads. Long read, single molecule sequencing technologies like those offered by Pacific Biosciences or Oxford Nanopore Technologies produce reads with a length of several thousand base pairs. Despite the higher error rate and sequencing cost, long read sequencing offers many advantages for the detection of structural variants. Yet, available software tools still do not fully exploit the possibilities. Results: We present SVIM, a tool for the sensitive detection and precise characterization of structural variants from long read data. SVIM consists of three components for the collection, clustering and combination of structural variant signatures from read alignments. It discriminates five different variant classes including similar types, such as tandem and interspersed duplications and novel element insertions. SVIM is unique in its capability of extracting both the genomic origin and destination of duplications. It compares favorably with existing tools in evaluations on simulated data and real datasets from PacBio and Nanopore sequencing machines. Availability and implementation: The source code and executables of SVIM are available on Github: github.com/eldariont/svim. SVIM has been implemented in Python 3 and published on bioconda and the Python Package Index. Supplementary information: Supplementary data are available at Bioinformatics online

    Microbial genomic taxonomy

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    A need for a genomic species definition is emerging from several independent studies worldwide. In this commentary paper, we discuss recent studies on the genomic taxonomy of diverse microbial groups and a unified species definition based on genomics. Accordingly, strains from the same microbial species share >95% Average Amino Acid Identity (AAI) and Average Nucleotide Identity (ANI), >95% identity based on multiple alignment genes, 70% in silico Genome-to-Genome Hybridization similarity (GGDH). Species of the same genus will form monophyletic groups on the basis of 16S rRNA gene sequences, Multilocus Sequence Analysis (MLSA) and supertree analysis. In addition to the established requirements for species descriptions, we propose that new taxa descriptions should also include at least a draft genome sequence of the type strain in order to obtain a clear outlook on the genomic landscape of the novel microbe. The application of the new genomic species definition put forward here will allow researchers to use genome sequences to define simultaneously coherent phenotypic and genomic groups

    Removing batch effects for prediction problems with frozen surrogate variable analysis

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    Batch effects are responsible for the failure of promising genomic prognos- tic signatures, major ambiguities in published genomic results, and retractions of widely-publicized findings. Batch effect corrections have been developed to re- move these artifacts, but they are designed to be used in population studies. But genomic technologies are beginning to be used in clinical applications where sam- ples are analyzed one at a time for diagnostic, prognostic, and predictive applica- tions. There are currently no batch correction methods that have been developed specifically for prediction. In this paper, we propose an new method called frozen surrogate variable analysis (fSVA) that borrows strength from a training set for individual sample batch correction. We show that fSVA improves prediction ac- curacy in simulations and in public genomic studies. fSVA is available as part of the sva Bioconductor package

    Development of the "carcinogenome": genomic signatures of carcinogenicity

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    Thesis (M.A.)--Boston UniversityThis project presents a new method of developing genomic signatures of carcinogenicity and offers a way of understanding the mechanisms of action for environmental chemicals, and a method for characterizing the carcinogenicity of said chemicals. Specifically, this project is an effort to “use a high-dimensional assay that allows for the genome-wide characterization of the transcriptional response to chemical exposure at a cost unmatched by other technologies, paired with the biological and computational expertise necessary to maximally leverage the information produced by the assay.”11 The primary aim of these preliminary experiments was to determine if the protocol of treating the cells at Boston University under strict IBC-approved conditions and then gathering data at the Broad Institute (Boston, Massachusetts) is a reasonable technique for obtaining high-throughput genomic signatures with chemicals of unknown carcinogenicity status. The results of this experiment demonstrate this methodology for obtaining genomic signatures has the potential to be a replicable, high-throughput procedure to assist in creating a "carcinogenome" database (CGDB)
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