Project description:Primary objectives: The primary objective is to investigate circulating tumor DNA (ctDNA) via deep sequencing for mutation detection and by whole genome sequencing for copy number analyses before start (baseline) with regorafenib and at defined time points during administration of regorafenib for treatment efficacy in colorectal cancer patients in terms of overall survival (OS).
Primary endpoints: circulating tumor DNA (ctDNA) via deep sequencing for mutation detection and by whole genome sequencing for copy number analyses before start (baseline) with regorafenib and at defined time points during administration of regorafenib for treatment efficacy in colorectal cancer patients in terms of overall survival (OS).
Project description:Whole transcriptome assessment of the Yersinia pseudotuberculosis strain YPIII. The Y. pseudotuberculosis rovA regulon was determined in Yersinia minimal minimum developed for the study. RovA is a key regulator for Yersinia virulence.
Project description:Following a pacemaker implantation, a 75-years-old patient suffered from five successive bacteremia episodes between in 1999 and 2013, during which five bacterial strains were isolated. Phenotypic and whole-genome sequencing analysis of four isolates identified the strains as Yersinia enterocolitica bioserotype 4/O:3. Phylogenetic reconstruction showed that the patient was chronically infected by the same strain, which evolved within the host during 14 years. Single-nucleotide polymorphhism (SNP) analysis indicates that the last two isolates which displayed severe growth defects in vitro and acquired resistance to quinolones, evolved in parallel and formed two independent lineages within the host. Pan-genome analysis and genome comparison showed that their common evolution was characterized by 41 small insertion/deletion events and loss of three large DNA fragments. These mutations, which may account for the observed growth defect and also for the appearance of vegetations on the pacemaker, support antibiotics tolerance. Quinolone resistance was acquired through a so far undescribed deletion in the gyrA gene. 140 genes containing mutations vertically acquired from a common ancestor were also identified in the two lineages. A phylogenetic analysis by maximum likelihood identified two genes presenting a positive selection signal, suggesting that these mutations provided a survival advantage to bacteria during chronic infection. This is the first report allowing identification of genetic changes associated to within-host adaptation of a pathogenic Yersinia species.
Project description:Whole transcriptome assessment of the Yersinia pseudotuberculosis strain YPIII. The Y. pseudotuberculosis csrA regulon was determined in Yersinia minimal minimum developed for the study. CsrA is a key regulator coordinating virulence and metabolism.
Project description:Whole transcriptome assessment of the Yersinia pseudotuberculosis strain YPIII. The Y. pseudotuberculosis crp regulon was determined in Yersinia minimal minimum developed for the study. Crp is a key regulator coordinating virulence and metabolism.
Project description:Investigation of whole genome gene expression level changes in Yersinia intermedia strain ATCC 29909 in response to oxygen. The experiments and results have not been published yet (manuscript has been submitted to journal office and is under revision)
Project description:Investigation of whole genome gene expression level changes in Yersinia intermedia strain ATCC 29909 in response to oxygen. The experiments and results have not been published yet (manuscript has been submitted to journal office and is under revision) A 6 chip (whole-genome-tiled array) study using total RNA recovered from the following: 6 separate cultures of Yersinia intermedia strain ATCC 29909 grown in minimal medium with glucose (3 grown in the presence of oxygen and 3 grown without oxygen). Each whole-genome-tiled arrays contained ~320,000 probes representing 3953 genes that included 3887 protein coding genes (and 18 likely pseudogenes), 12 non-coding RNAs and 36 tRNAs. Data from probes corresponding to intergenic regions (and some pseudogenes, rRNA genes and unannotated genes) of the genome were not considered in the present analysis.
Project description:Whole transcriptome assessment of the Yersinia pseudotuberculosis strain YPIII grown under aerobic or anaerobic conditions to stationary phase.
