Project description:To test if scRNA-seq contains sufficient phylogenetic information to reconstruct a population history of cancer, immunosuppressed NU/J mice were injected with human cancer cells (MDA-MB-231-LM2). The tumors that develop are derived from the same population and thus share a common ancestor, but evolved independently in each mouse and should form separate clades on reconstructed phylogenetic trees when analysed together. We explore and compare results of phylogenetic analyses based on both expression levels and SNVs called from our scRNA-seq data. Both techniques are shown to be useful for reconstructing phylogenetic relationships between cells, refecting the clonal composition of a tumor. Without an explicit error model, standardized expression values appears to be more powerful and informative than the SNV values at a lower computational cost, due to being a by-product of standard expression analysis. Our results suggest that scRNA-seq can be a competitive alternative or useful addition to conventional scDNA-seq phylogenetic reconstruction. Our results open up a new direction of somatic phylogenetics based on scRNA-seq data. Further research is required to refne and improve these approaches to capture the full picture of somatic evolutionary dynamics in cancer.
Project description:Genome profiling of primary tumors and matched metastases from a BALB-NeuT murine breast cancer transplantation model. The first goal of this study was to investigate the differences of primary tumors and metastases with regard to copy number alterations. The second goal was to infer phylogenetic trees reflecting the evolutionary paths of primary tumors and their derived metastases (only mice with at least one metastasis were used for phylogenetic analyses).
Project description:Restriction site Associated DNA (RAD) tags are a genome-wide representation of every site of a particular restriction enzyme by short DNA tags. Most organisms segregate large numbers of DNA sequence polymorphisms that disrupt restriction sites, which allow RAD tags to serve as genetic markers spread at a high-density throughout the genome. Here, we demonstrate the applicability of RAD markers for both individual and bulk-segregant genotyping. First, we show that these markers can be identified and typed on pre-existing microarray formats. Second, we present a method that uses RAD marker DNA to rapidly produce a low-cost microarray genotyping resource that can be used to efficiently identify and type thousands of RAD markers. We demonstrate the utility of the former approach by using a tiling path array for the fruit fly to map a recombination breakpoint, and the latter approach by creating and utilizing an enriched RAD marker array for the threespine stickleback. The high number of RAD markers enabled localization of a previously identified region, as well as a second novel region also associated with the lateral plate phenotype. Taken together, our results demonstrate that RAD markers, and the method to develop a RAD marker microarray resource, allow high-throughput, high-resolution genotyping in both model and non-model systems. Keywords: microarray genotyping
2007-01-24 | GSE5773 | GEO
Project description:Phylogenetic analyses of species associated with Protacanthopterygii