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).
| 2533916 | ecrin-mdr-crc
Project description:Sequencing of actinobacteria type strains
Project description:A previously described low-fitness, high stress-resistant, variant of Listeria monocytogenes LO28 WT was subjected to an experimental evolution regime, selecting (in two parallel lines) for increased fitness in unstressed conditions. Evolved variants with increased fitness reverted to WT-like stress resistance. Whole genome sequencing and proteomics were used to identify differences between the ancestral and evolved strains.
Project description:Despite high vaccination coverage, pertussis is on the rise in many countries including Czech Republic. To better understand B. pertussis resurgence we compared the changes in genome structures between Czech vaccine and circulating strains and subsequently, we determined how these changes translated into global transcriptomic and proteomic profiles. The whole-genome sequencing revealed that both historical and recent isolates of B. pertussis display substantial variation in genome organization and cluster separately. The RNA-seq and LC-MS/MS analyses indicate that these variations translated into discretely separated transcriptomic and proteomic profiles. Compared to vaccine strains, recent isolates displayed increased expression of flagellar genes and decreased expression of polysaccharide capsule operon. Czech strains (Bp46, K10, Bp155, Bp318 and Bp6242)exhibited increased expression of T3SS and sulphate metabolism genes when compared to Tohama I. In spite of 50 years of vaccination the Czech vaccine strains (VS67, VS393 and VS401) differ from recent isolates to a lesser extent than from another vaccine strain Tohama I.
Project description:Staphylococcus aureus is a high-priority pathogen causing severe infections with high morbidity and mortality worldwide. Many S. aureus strains are methicillin-resistant (MRSA) or even multi-drug resistant. It is one of the most successful and prominent modern pathogens. An effective fight against S. aureus infections requires novel targets for antimicrobial and antistaphylococcal therapies. Recent advances in whole-genome sequencing and high-throughput techniques facilitate the generation of genome-scale metabolic models (GEMs). Among the multiple applications of GEMs is drug-targeting in pathogens. Hence, comprehensive and predictive metabolic reconstructions of S. aureus could facilitate the identification of novel targets for antimicrobial therapies. This review aims at giving an overview of all available GEMs of multiple S. aureus strains. We downloaded all 114 available GEMs of S. aureus for further analysis. The scope of each model was evaluated, including the number of reactions, metabolites, and genes.Furthermore, all models were quality-controlled using Mᴇᴍᴏᴛᴇ, an open-source application with standardized metabolic tests. Growth capabilities and model similarities were examined. This review should lead as a guide for choosing the appropriate GEM for a given research question. With the information about the availability, the format, and the strengths and potentials of each model, one can either choose an existing model or combine several models to create models with even higher predictive values. This facilitates model-driven discoveries of novel antimicrobial targets to fight multi-drug resistant S. aureus strains.
Project description:Staphylococcus aureus is a high-priority pathogen causing severe infections with high morbidity and mortality worldwide. Many S. aureus strains are methicillin-resistant (MRSA) or even multi-drug resistant. It is one of the most successful and prominent modern pathogens. An effective fight against S. aureus infections requires novel targets for antimicrobial and antistaphylococcal therapies. Recent advances in whole-genome sequencing and high-throughput techniques facilitate the generation of genome-scale metabolic models (GEMs). Among the multiple applications of GEMs is drug-targeting in pathogens. Hence, comprehensive and predictive metabolic reconstructions of S. aureus could facilitate the identification of novel targets for antimicrobial therapies. This review aims at giving an overview of all available GEMs of multiple S. aureus strains. We downloaded all 114 available GEMs of S. aureus for further analysis. The scope of each model was evaluated, including the number of reactions, metabolites, and genes. Furthermore, all models were quality-controlled using Mᴇᴍᴏᴛᴇ, an open-source application with standardized metabolic tests. Growth capabilities and model similarities were examined. This review should lead as a guide for choosing the appropriate GEM for a given research question. With the information about the availability, the format, and the strengths and potentials of each model, one can either choose an existing model or combine several models to create models with even higher predictive values. This facilitates model-driven discoveries of novel antimicrobial targets to fight multi-drug resistant S. aureus strains.
Project description:Staphylococcus aureus is a high-priority pathogen causing severe infections with high morbidity and mortality worldwide. Many S. aureus strains are methicillin-resistant (MRSA) or even multi-drug resistant. It is one of the most successful and prominent modern pathogens. An effective fight against S. aureus infections requires novel targets for antimicrobial and antistaphylococcal therapies. Recent advances in whole-genome sequencing and high-throughput techniques facilitate the generation of genome-scale metabolic models (GEMs). Among the multiple applications of GEMs is drug-targeting in pathogens. Hence, comprehensive and predictive metabolic reconstructions of S. aureus could facilitate the identification of novel targets for antimicrobial therapies. This review aims at giving an overview of all available GEMs of multiple S. aureus strains. We downloaded all 114 available GEMs of S. aureus for further analysis. The scope of each model was evaluated, including the number of reactions, metabolites, and genes.Furthermore, all models were quality-controlled using Mᴇᴍᴏᴛᴇ, an open-source application with standardized metabolic tests. Growth capabilities and model similarities were examined. This review should lead as a guide for choosing the appropriate GEM for a given research question. With the information about the availability, the format, and the strengths and potentials of each model, one can either choose an existing model or combine several models to create models with even higher predictive values. This facilitates model-driven discoveries of novel antimicrobial targets to fight multi-drug resistant S. aureus strains.
2022-02-16 | MODEL2007150002 | BioModels
Project description:Whole-genome analyses of novel actinobacteria
| PRJNA524765 | ENA
Project description:Whole-genome analyses of novel actinobacteria
Project description:In this study, we have applied the top-down approach to reduce the genome of B. subtilis in order to obtain minimal strains with robust growth on complex medium at 37°C. For this purpose, we have evaluated the function of each gene of the B. subtilis genome and identified essential, important and dispensable genomic regions. Using an efficient markerless and scarless deletion method and a system allowing induction of genetic competence in the complete cell population, we have constructed two genome-reduced strains lacking about 36% of dispensable genetic information. Multi-omics analyses with the genome-reduced strains revealed substantial changes in the transcriptome, the proteome and in the metabolome. The massive reorganization of metabolism in the two genome-reduced strains can be explained by the underlying genotypes that were determined by genome re-sequencing. Moreover, the transcriptome and proteome analyses uncovered novel dispensable genomic regions that can be removed to further streamline the B. subtilis genome. In conclusion, both minimal strains show interesting metabolic features and they serve as excellent starting points to generate an ultimate reduced-genome B. subtilis cell containing only genes required for robust growth on complex medium.