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:Interventions: Genomic test CANCERPLEX-JP OncoGuide NCC oncopanel system FndationONe CDx genome profile GUARDANT360 MSI Analysis System BRACAnalysis
Primary outcome(s): Development of genome database
Study Design: Single arm Non-randomized
Project description:We set out to investigate the genetic adaptions of the known marine fungus Paradendryphiella salina CBS112865 to the degradation of brown macro-algae, expecting to find a repertoire of carbohydrate active enzymes highly specialized to the degradation of algal polysaccharides. We performed whole genome, transcriptome sequencing and shotgun proteomic analysis of the secretome of P. salina growing on three species of brown algae and under carbon starvation. The genome comparison to close terrestrial fungal relatives, revealed P. salina to have a similar, but reduced carbohydrate active enzyme (CAZyme) profile, except for the presence of three putative alginate lyase 7 genes, most likely acquired via ancient horizontal gene transfer event from a marine bacterium and a polysaccharide lyase 8 gene with similarity to ascomycete chondroitin AC lyases. The proteomic analysis revealed both PL7 and PL8 enzymes to be highly abundant in the algal fermentations together with enzymes necessary for degradation of laminarin, cellulose, lipids and peptides. Our findings indicate that the base CAZyme repertoire of saprobic and plant pathogenic ascomycetes with the necessary addition of alginate lyases provide the fungi with the enzymatic capabilities to thrive on brown algae polysaccharides and even cope with the algal defense mechanisms.
Project description:Atypical teratoid/rhabdoid tumor (ATRT) is one of the most common brain tumors in infants. Although the prognosis of ATRT patients is poor, some patients respond favorably to current treatments, suggesting molecular inter-tumor heterogeneity. To investigate this further, we genetically and epigenetically analyzed a large series of human ATRTs. Three distinct molecular subgroups of ATRTs, associated with differences in demographics, tumor location, and type of SMARCB1 alterations, were identified. Whole-genome DNA and RNA sequencing found no recurrent mutations in addition to SMARCB1 that would explain the differences between subgroups. Whole-genome bisulfite sequencing and H3K27Ac chromatin-immunoprecipitation sequencing of primary tumors, however, revealed clear differences, leading to the identification of subgroup-specific regulatory networks and potential therapeutic targets.
Project description:Genomic and proteomic characterization of the Aspergillus niger isolate, JSC-093350089, collected from U.S. segment surfaces of the International Space Station (ISS) is reported, along with a comparison to the experimentally established strain ATCC 1015. Whole-genome sequencing of JSC-093350089 revealed enhanced genetic variance when compared to publicly available sequences of A. niger strains. Analysis of the isolate’s proteome revealed significant differences in the molecular phenotype of JSC-093350089, including increased abundance of proteins involved in the A. niger starvation response, oxidative stress resistance, cell wall integrity and modulation, and nutrient acquisition. Together, these data reveal the existence of a distinct strain of A. niger onboard the ISS and provide insight into the molecular phenotype that is selected for by melanized fungal species inhabiting spacecraft environments.
Project description:Counting DNA reads using whole genome sequencing is providing new insight into DNA double-strand break repair (DSBR) in the model organism Escherichia coli. We describe the application of RecA chromatin immunoprecipitation coupled to genomic DNA sequencing (RecA-ChIP-seq) and marker frequency analysis (MFA) to analyse the genomic consequences of DSBR.
Project description:Counting DNA reads using whole genome sequencing is providing new insight into DNA double-strand break repair (DSBR) in the model organism Escherichia coli. We describe the application of RecA chromatin immunoprecipitation coupled to genomic DNA sequencing (RecA-ChIP-seq) and marker frequency analysis (MFA) to analyse the genomic consequences of DSBR.
Project description:The Nanopig™ model is an emerging non-rodent platform for (bio)pharmaceutical safety assessment, with potential advantages for translational research. Here, we report initial characterization results using whole genome sequencing (WGS) and tissue-based proteomics, focusing on drug metabolism and immune system relevance. WGS produced a high-quality Nanopig™ genome assembly (2.8–2.9 Gb), with >98 % alignment to the Duroc pig reference genome, and identified key metabolic and immune-related genes, including 47 cytochrome P450 (CYP450) genes with high homology to human CYP450 families. Proteomic profiling of 15 pharmaceutically relevant tissues revealed human orthologous drug metabolism enzymes and transporters (DMETs), as well as immune-related proteins, indicating similarities to human CYP450 enzyme abundance and tissue distribution. Functional evaluation of hepatic CYP450 activity yielded kinetic parameters (Km, Vmax) in the range observed in humans and beagle dogs. These early findings represent a foundational multi-omics dataset for the Nanopig™, suggesting its future use as a translational model in preclinical safety assessment. This work provides an early framework for species selection strategies and model optimization, with the long-term goal of reducing reliance on traditional non-rodent species in drug development.
Project description:he Nanopig™ model is an emerging non-rodent platform for (bio)pharmaceutical safety assessment, with potential advantages for translational research. Here, we report initial characterization results using whole genome sequencing (WGS) and tissue-based proteomics, focusing on drug metabolism and immune system relevance. WGS produced a high-quality Nanopig™ genome assembly (2.8–2.9 Gb), with >98 % alignment to the Duroc pig reference genome, and identified key metabolic and immune-related genes, including 47 cytochrome P450 (CYP450) genes with high homology to human CYP450 families. Proteomic profiling of 15 pharmaceutically relevant tissues revealed human orthologous drug metabolism enzymes and transporters (DMETs), as well as immune-related proteins, indicating similarities to human CYP450 enzyme abundance and tissue distribution. Functional evaluation of hepatic CYP450 activity yielded kinetic parameters (Km, Vmax) in the range observed in humans and beagle dogs. These early findings represent a foundational multi-omics dataset for the Nanopig™, suggesting its future use as a translational model in preclinical safety assessment. This work provides an early framework for species selection strategies and model optimization, with the long-term goal of reducing reliance on traditional non-rodent species in drug development.