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:The study of hybrid zones advances understanding of the speciation process, and approaches incorporating genomic data are increasingly used to draw significant conclusions about the impact of hybridisation. Despite the progress made, the complex interplay of factors that can lead to substantially variable hybridisation outcomes are still not well understood, and many systems and/or groups remain comparatively poorly studied. Our study aims to broaden the literature on avian hybrid zones, investigating a potentially geographically and temporally complex putative hybrid zone between two native Australian non-sister parrot species, the pale-headed and eastern rosellas (Platycercus adscitus and Platycercus eximius, respectively). We analysed six plumage traits and >1400 RADseq loci and detected hybrid individuals and an unexpectedly complex geographic structure. The hybrid zone is larger than previously described due to either observer bias or its movement over recent decades. It comprises different subregions where genetic and plumage signals of admixture vary markedly in their concordance. Evidence of contemporary hybridisation (later generation and backcrossed individuals) both within and beyond the previously defined zone, when coupled with a lack of F1 hybrids and differential patterns of introgression among potentially diagnostic loci, indicates a lack of post-zygotic barriers to gene flow between species. Despite ongoing gene flow, species boundaries are likely maintained largely by strong pre-mating barriers. These findings are discussed in detail and future avenues for research into this system are proposed, which would be of benefit to the speciation and hybrid zone literature.
Project description:The naked mole-rat (NMR; Heterocephalus glaber) has recently gained considerable attention in the scientific community for its unique potential to unveil novel insights in the fields of medicine, biochemistry, and evolution. NMRs exhibit unique adaptations that include protracted fertility, cancer resistance, eusociality, and anoxia. This suite of adaptations is not found in other rodent species, suggesting that interrogating conserved and accelerated regions in the NMR genome will find regions of the NMR genome fundamental to their unique adaptations. However, the current NMR genome assembly has limits that make studying structural variations, heterozygosity, and non-coding adaptations challenging. We present a complete diploid naked-mole rat genome assembly by integrating long-read and 10X-linked read genome sequencing of a male NMR and its parents, and Hi-C sequencing in the NMR hypothalamus (N=2). Reads were identified as maternal, paternal or ambiguous (TrioCanu). We then polished genomes with Flye, Racon and Medaka. Assemblies were then scaffolded using the following tools in order: Scaff10X, Salsa2, 3d-DNA, Minimap2-alignment between assemblies, and the Juicebox Assembly Tools. We then subjected the assemblies to another round of polishing, including short-read polishing with Freebayes. We assembled the NMR mitochondrial genome with mitoVGP. Y chromosome contigs were identified by aligning male and female 10X linked reads to the paternal genome and finding male-biased contigs not present in the maternal genome. Contigs were assembled with publicly available male NMR Fibroblast Hi-C-seq data (SRR820318). Both assemblies have their sex chromosome haplotypes merged so that both assemblies have a high-quality X and Y chromosome. Finally, assemblies were evaluated with Quast, BUSCO, and Merqury, which all reported the base-pair quality and contiguity of both assemblies as high-quality. The assembly will next be annotated by Ensembl using public RNA-seq data from multiple tissues (SRP061363). Together, this assembly will provide a high-quality resource to the NMR and comparative genomics communities.