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:To better understand genome coordination and OXPHOS recovery during mitochondrial dysfunction, we examined ATFS-1, a transcription factor that regulates mitochondria-to nuclear communication during the mitochondrial UPR, via ChIP-sequencing. Wildtype worms treated spg-7(RNAi) are analyzed in the presence and absence of ATFS-1 antibody to identify ATFS-1 targets. Individual samples were analyzed. Wildtype worms treated spg-7(RNAi) in the absence of antibody is used as a control.
Project description:To better understand genome coordination and OXPHOS recovery during mitochondrial dysfunction, we examined ATFS-1, a transcription factor that regulates mitochondria-to nuclear communication during the mitochondrial UPR, via ChIP-sequencing.
Project description:The human mitochondrial genome comprises a distinct genetic system transcribed as precursor polycistronic transcripts that are subsequently cleaved to generate individual mRNAs, tRNAs and rRNAs. Here we provide a comprehensive analysis of the human mitochondrial transcriptome across multiple cell lines and tissues. Using directional deep sequencing and parallel analysis of RNA ends, we demonstrate wide variation in mitochondrial transcript abundance, and precisely resolve transcript processing and maturation events. We identify novel transcripts, including small RNAs, and observe the enrichment of several nuclear RNAs in mitochondria. Using high-throughput in vivo DNaseI footprinting, we establish the global profile of DNA-binding protein occupancy across the mitochondrial genome at single nucleotide resolution, revealing novel regulatory features at mitochondrial transcription initiation sites and functional insights into disease-associated variants. Together, this integrated analysis of the mitochondrial transcriptome reveals unexpected complexity in the regulation, expression, and processing of mitochondrial RNA, and itM-CM-^BM-BM- provides a resource for the future study of mitochondrial function (accessed at mitochondria.matticklab.com). Examination of the mitochondiral transcriptome by long and small RNA sequencing, PARE sequencing and DNAseI hypersensitivity mapping.
Project description:We introduce FACIL (http://www.cmbi.ru.nl/FACIL), a fast, reliable tool to evaluate nucleic acid sequences for non-standard codes that detects alternative genetic codes even in species distantly related to known organisms. Results are visualized in a Genetic Code Logo. To illustrate the use of our method, we analysed several contigs derived from the mitochondrial genome of the foraminifer Globobulimina pseudospinescens. These are particularly challenging data, as the genome is highly fragmented and incomplete. Approximately 10,000 single-cell Globobulimina pseudospinescens organisms were isolated by hand from Gullmar Fjord Sweden sediment. After washing, total DNA was extracted and sequenced by Illumina sequencing. The reads were assembled using Edena. To illustrate the use of our method, we analysed several contigs derived from the mitochondrial genome of the foraminifer Globobulimina pseudospinescens, an organism without any sequenced relatives in the databases. These are particularly challenging data, as the genome is highly fragmented and incomplete. DNA isolated from approximately 10,000 single-cell Globobulimina pseudospinescens organisms