PIRATE A fast and scalable pangenomics toolbox for clustering diverged orthologues in bacteria, bioRxiv, 2019-04-05

AbstractCataloguing the distribution of genes within natural bacterial populations is essential for understanding evolutionary processes and the genetic basis of adaptation. Here we present a pangenomics toolbox, PIRATE (Pangenome Iterative Refinement And Threshold Evaluation), which identifies and classifies orthologous gene families in bacterial pangenomes over a wide range of sequence similarity thresholds. PIRATE builds upon recent scalable software developments to allow for the rapid interrogation of thousands of isolates. PIRATE clusters genes (or other annotated features) over a wide range of amino-acid or nucleotide identity thresholds and uses the clustering information to rapidly classify paralogous gene families into either putative fissionfusion events or gene duplications. Furthermore, PIRATE orders the pangenome using a directed graph, provides a measure of allelic variation and estimates sequence divergence for each gene family. We demonstrate that PIRATE scales linearly with both number of samples and computation resources, allowing for analysis of large genomic datasets, and compares favorably to other popular tools. PIRATE provides a robust framework for analysing bacterial pangenomes, from largely clonal to panmictic species.AvailabilityPIRATE is implemented in Perl and is freely available under an GNU GPL 3 open source license from <jatsext-link xmlnsxlink=httpwww.w3.org1999xlink ext-link-type=uri xlinkhref=httpsgithub.comSionBaylissPIRATE>httpsgithub.comSionBaylissPIRATE<jatsext-link>.<jatssec sec-type=supplementary-material>Supplementary InformationSupplementary data is available online.

biorxiv bioinformatics 100-200-users 2019

Muscle fiber hypertrophy in response to 6 weeks of high-volume resistance training in trained young men is largely attributed to sarcoplasmic hypertrophy, bioRxiv, 2019-04-02

ABSTRACTCellular adaptations that occur during skeletal muscle hypertrophy in response to high-volume resistance training are not well-characterized. Therefore, we sought to explore how actin, myosin, sarcoplasmic protein, mitochondrial, and glycogen concentrations were altered in individuals that exhibited mean skeletal muscle fiber cross-sectional area (fCSA) hypertrophy following 6 weeks of high-volume resistance training. Thirty-one previously resistance-trained, college-aged males (mean ± standard deviation 21±2 years, 5±3 training years) had vastus lateralis (VL) muscle biopsies obtained prior to training (PRE), at week 3 (W3), and at week 6 (W6). Muscle tissue from 15 subjects exhibiting PRE to W6 VL mean fCSA increases ranging from 320-1600 μm2 was further interrogated using various biochemical and histological assays as well as proteomic analysis. Seven of these individuals donated a VL biopsy after refraining from training 8 days following the last training session (W7) to determine how deloading affected biomarkers. The 15 fCSA hypertrophic responders experienced a +23% increase in mean fCSA from PRE to W6 (p&lt;0.001) and, while muscle glycogen concentrations remained unaltered, citrate synthase activity levels decreased by 24% (p&lt;0.001) suggesting mitochondrial volume decreased. Interestingly, both myosin and actin concentrations decreased ~30% from PRE to W6 (p&lt;0.05). Phalloidin-actin staining similarly revealed actin concentrations per fiber decreased from PRE to W6. Proteomic analysis of the sarcoplasmic fraction from PRE to W6 indicated 40 proteins were up-regulated (p&lt;0.05), KEGG analysis indicated that the glycolysisgluconeogenesis pathway was upregulated (FDR sig. &lt;0.001), and DAVID indicated that the following functionally-annotated pathways were upregulated (FDR value &lt;0.05) a) glycolysis (8 proteins), b) acetylation (23 proteins), c) gluconeogenesis (5 proteins) and d) cytoplasm (20 proteins). At W7, sarcoplasmic protein concentrations remained higher than PRE (+66%, p&lt;0.05), and both actin and myosin concentrations remained lower than PRE (~−50%, p&lt;0.05). These data suggest that short-term high-volume resistance training may a) reduce muscle fiber actin and myosin protein concentrations in spite of increasing fCSA, and b) promote sarcoplasmic expansion coincident with a coordinated up-regulation of sarcoplasmic proteins involved in glycolysis and other metabolic processes related to ATP generation. Interestingly, these effects seem to persist up to 8 days following training.

biorxiv molecular-biology 100-200-users 2019

 

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