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Integrated Analysis of Population Genomics, Transcriptomics and Virulence Provides Novel Insights into Streptococcus pyogenes Pathogenesis

ABSTRACT: Integrated Analysis of Population Genomics, Transcriptomics and Virulence Provides Novel Insights into Streptococcus pyogenes Pathogenesis

PROVIDER: PRJNA449903 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6988810.fastq.gz	Fastqsanger.gz
	SRR6988820.fastq.gz	Fastqsanger.gz
	SRR6988830.fastq.gz	Fastqsanger.gz
	SRR6988840.fastq.gz	Fastqsanger.gz
	SRR6988850.fastq.gz	Fastqsanger.gz

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Integrated Analysis of Population Genomics, Transcriptomics and Virulence Provides Novel Insights into Streptococcus pyogenes Pathogenesis [isogenic]

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Integrated Analysis of Population Genomics, Transcriptomics and Virulence Provides Novel Insights into Streptococcus pyogenes Pathogenesis [50 strains]

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Integrated Analysis of Population Genomics, Transcriptomics and Virulence Provides Novel Insights into Streptococcus pyogenes Pathogenesis

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2018-12-31 | GSE113058 | GEO

Integrated analysis of population genomics, transcriptomics and virulence provides novel insights into Streptococcus pyogenes pathogenesis.

Project description:Streptococcus pyogenes causes 700 million human infections annually worldwide, yet, despite a century of intensive effort, there is no licensed vaccine against this bacterium. Although a number of large-scale genomic studies of bacterial pathogens have been published, the relationships among the genome, transcriptome, and virulence in large bacterial populations remain poorly understood. We sequenced the genomes of 2,101 emm28 S. pyogenes invasive strains, from which we selected 492 phylogenetically diverse strains for transcriptome analysis and 50 strains for virulence assessment. Data integration provided a novel understanding of the virulence mechanisms of this model organism. Genome-wide association study, expression quantitative trait loci analysis, machine learning, and isogenic mutant strains identified and confirmed a one-nucleotide indel in an intergenic region that significantly alters global transcript profiles and ultimately virulence. The integrative strategy that we used is generally applicable to any microbe and may lead to new therapeutics for many human pathogens.

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Integrated Analysis of Population Genomics, Transcriptomics and Virulence Provides Novel Insights into Streptococcus pyogenes Pathogenesis [isogenic]

Project description:Purpose: We used GAS as a model bacterial pathogen to investigate the complex relationship between genome, transcriptome, and virulence in a large population of type emm28 strains recovered from humans over 26 years in geographically diverse locations. Methods: An isogenic mutant strain (MGAS27961-10T) with a 10-T homopolymeric tract was generated using allelic exchange. Primers were used to amplify a 2,690-bp fragment using genomic DNA of MGAS28085 an emm28 clinical isolate with the naturally occurring 10 “T” variant region. The resulting PCR product was cloned into suicide plasmid pBBL740 and transformed into the parental strain MGAS27961. RNA-seq was performed on the isogenic mutant strain MGAS27961-10T and parental strain (MGAS27961-9T). Quality of the total RNA, rRNA-depleted RNA, and cDNA libraries was evaluated with RNA Nano, RNA Pico, and DNA high-sensitivity kits (Agilent Technologies), respectively, using an Agilent 2100 Bioanalyzer. For each sample, the cDNA library concentration was measured fluorometrically with Qubit™ dsDNA HS assay kits (Invitrogen). The cDNA libraries were diluted, pooled, and sequenced with an Illumina NextSeq 500 instrument.

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Project description:Megalobrama, a genus of cyprinid fish, is an economically important freshwater fish widely distributed in major waters of China. Here, we report the genome resequencing of 180 Megalobrama fish including M. amblycephala, M. skolkovii, M. hoffmanni, and M. pellegrini. Population structure indicated that geographically divergent Megalobrama populations were separated into six subgroups. A phylogenetic tree showed that M. skolkovii was more closely related to M. pellegrini than other species and M. hoffmanni was clustered apart from other Megalobrama species, showing a high nucleotide diversity in geographic groups. Treemix validated gene flow from M. amblycephala to M. skolkovii, suggesting that introgression may provide an important source of genetic variation in the M. skolkovii populations. According to the demographic history analysis, it is speculated that Megalobrama might have been originally distributed in the Pearl River with some spread to Hainan Island and northern China due to lower sea levels during the glacial period. Whole-genome selective sweeps analysis demonstrated that M. amblycephala likely developed an enhanced energy metabolism mostly through fatty acid degradation pathways whereas M. hoffmanni possibly regulate lipid absorption via the cholesterol metabolism pathway. Taken together, this study provides a valuable genomic resource for future genetic investigations aiming to improve genome-assisted breeding of Megalobrama species.

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