Project description:To make clear the genetic diversity and virulence evolution at the genome-wide level of A. pleuropneumoniae Keywords: comparative genomic hybridization
Project description:ZIKV strains belong to three phylogenetic lineages: East African, West African, and Asian/American. RNA virus genomes exist as populations of genetically-related sequences whose heterogeneity may impact viral fitness, evolution, and virulence. The genetic diversity of representative ZIKVs (N=7) from each lineage was examined using next generation sequencing (NGS) paired with downstream Shannon entropy calculation and single nucleotide variant (SNV) analysis. This comprehensive analysis of ZIKV genetic diversity provides insight into the genetic diversity of ZKIV and repository of SNV positions across lineages.
Project description:The rise of antibiotic resistance in many bacterial pathogens has been driven by the spread of a few successful strains, suggesting that some bacteria are genetically pre-disposed to evolving resistance. We tested this hypothesis by challenging a diverse set of 222 strains of Staphylococcus aureus with the antibiotic ciprofloxacin in a large-scale evolution experiment. Surprisingly, we found that a single efflux pump, norA, causes widespread variation in evolvability across the diversity of S. aureus. In most lineages of S. aureus, elevated norA expression potentiated evolution by increasing the fitness benefit provided by resistance mutations in DNA topoisomerase under ciprofloxacin treatment. Amplification of norA provided a further mechanism of rapid evolution, but this was restricted to strains from CC398. Crucially, chemically inhibiting NorA effectively prevented the evolution of resistance across the diversity of S. aureus. Our study shows that the underlying genetic diversity of pathogenic bacteria plays a key role in shaping resistance evolution. Understanding this link makes it possible to predict which strains are likely to evolve resistance and to optimize inhibitor use to prevent this outcome.
Project description:Clonal diversity contributes to treatment resistance and cancer recurrence. Precise delineation of clonal substructure is essential to understand the resistance mechanism, however, bulk DNA sequencing cannot accurately resolve the complex clonal architectures. Here we report the single-cell DNA sequencing of 123 acute myeloid leukemia (AML) patients and provide cell-level evidence of co-occurrence and mutual exclusivity among driver mutations. Reconstruction of tumor phylogeny uncovers linear and branching clonal evolution patterns, with the latter involving functional convergence. Single-cell DNA sequencing of xenotransplanted samples reveales clonal diversity in leukemia initiating cell populations. Simultaneous single-cell profiling of mutations and cell surface proteins provides cellular genotype-phenotype associations. Analysis of longitudinal samples visualizes the behavior of each individual clone in response to therapy, illustrating the underlying evolutionary process of therapeutic resistance and disease recurrence. Together, these data portray clonal diversity, architecture, and evolution of AML, and highlight their clinical relevance in the era of precision medicine.
Project description:Owing to their exceptional diversity and central role in vertebrate evolution, teeth are key biological systems. We exploited the diversity of bearded dragon dentitions to unreveal new aspects of major dental characters only represented in non-mammalian lineages.