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:Bombus longipennis mitochondrial genome sequencing and assembly
Project description:Human cells identify invading pathogens and activate immune signaling pathways through a wide array of pattern recognition receptors, such as DNA sensors. The interferon-inducible protein 16 (IFI16) is a nuclear DNA sensor that recognizes double-stranded DNA from a number of viral sources, including genomes of nuclear-replicating viruses such as the prevalent human pathogen, herpes simplex virus 1 (HSV-1). Upon binding to the DNA genome of HSV-1, IFI16 both induces antiviral cytokine expression and suppresses virus gene expression. Here, we use a multi-omics approach of DNA sequencing techniques paired with targeted mass spectrometry to obtain an extensive view of the interaction between IFI16 and the HSV-1 genome, and how this binding affects the viral DNA structure and protein expression. Through ChIP-seq, we find that IFI16 binds to the HSV-1 genome in a sequence-independent manner while simultaneously exhibiting broad enrichment at two loci: UL30, the viral DNA polymerase gene, and US1-US7. ATAC-seq analysis reveals that these two regions are among the most accessible stretches of DNA on the genome, thereby facilitating IFI16 binding. Accessibility of the entire HSV-1 genome is elevated upon IFI16-KO, indicating that expression of IFI16 globally induces chromatinization of viral DNA, regardless of IFI16 enrichment. Deletion of IFI16 also results in a global increase in the expression of HSV-1 proteins, as measured by parallel reaction monitoring-mass spectrometry. Altogether, we demonstrate that IFI16 interacts with the HSV-1 genome in a sequence-independent manner, and this interaction coordinates epigenetic silencing of the viral genome, resulting in decreased protein expression and virus replication.
Project description:Small RNA libraries were constructed from total RNA from Jasminum sambac plants exhibiting virus-like symptoms. After sequencing, small RNAs were assembled into contigs with MetaVelvet and assembled contigs were aligned against the NR database of NCBI using BLASTx. Top hits that reported a virus as subject were considered putative viral sequences. Based on such alignments, the whole genome of a virus, we tentatively name Jasmine Virus H was recovered and cloned. Two more small RNA libraries were made in a confirmatory experiment. One from Jasminum sambac and another one from Nicotiana benthamiana plants infected with the newly-cloned virus. The small RNA libraries were aligned against the full-length sequence of Jasmine Virus H to determine the spacial distribution of virus-derived small RNAs along the virus genome.