Precision medicine aims to identify the right drug, for the right patient, at the right dose, at the right time, which is particularly important in cancer therapy. Problems such as the variability of treatment respons...Precision medicine aims to identify the right drug, for the right patient, at the right dose, at the right time, which is particularly important in cancer therapy. Problems such as the variability of treatment response and resistance to medication have been longstanding challenges in oncology, especially for development of new medications. Solid tumors, unlike hematologic malignancies or brain tumors, are remarkably diverse in their cellular origins and developmental timing. The ability of next-generation sequencing(NGS) to analyze the comprehensive landscape of genetic alterations brings promises to diseases that have a highly complex and heterogeneous genetic composition such as cancer. Here we provide an overview of how NGS is able to facilitate precision medicine and change the paradigm of cancer therapy, especially for solid tumors, through technical advancements, molecular diagnosis, response monitoring and clinical trials.展开更多
Aims Darwin’s naturalization hypothesis proposes that successfully established alien species are less closely related to native species due to differences in their ecological niches.Studies have provided support both...Aims Darwin’s naturalization hypothesis proposes that successfully established alien species are less closely related to native species due to differences in their ecological niches.Studies have provided support both for and against this hypothesis.One reason for this is the tendency for phylogenetic clustering between aliens and natives at broad spatial scales with overdispersion at fine scales.However,little is known about how the phylogenetic relatedness of alien species alters the phylogenetic structure of the communities they invade,and at which spatial scales effects may manifest.Here,we examine if invaded understorey plant communities,i.e.containing both native and alien taxa,are phylogenetically clustered or overdispersed,how relatedness changes with spatial scale and how aliens affect phylogenetic patterns in understorey communities.Methods Field surveys were conducted in dry forest understorey communities in south-east Australia at five spatial scales(1,20,500,1500 and 4500 m2).Standardized effect sizes of two metrics were used to quantify phylogenetic relatedness between communities and their alien and native subcommunities,and to examine how phylogenetic patterns change with spatial scale:(i)mean pairwise distance and(ii)mean nearest taxon distance(MNTD).Important Findings Aliens were closely related to each other,and this relatedness tended to increase with scale.Native species and the full community exhibited either no clear pattern of relatedness with increasing spatial scale or were no different from random.At intermediate spatial scales(20-500 m2),the whole community tended towards random whereas the natives were strongly overdispersed and the alien subcommunity strongly clustered.This suggests that invasion by closely related aliens shifts community phylogenetic structure from overdispersed towards random.Aliens and natives were distantly related across spatial scales,supporting Darwin’s naturalization hypothesis,but only when phylogenetic distance was quantified as MNTD.Phylogenetic dissimilarity between aliens and natives increased with spatial scale,counter to expected patterns.Our findings suggest that the strong phylogenetic clustering of aliens is driven by human-mediated introductions involving closely related taxa that can establish and spread successfully.Unexpected scale-dependent patterns of phylogenetic relatedness may result from stochastic processes such as fire and dispersal events and suggest that competition and habitat filtering do not exclusively dominate phylogenetic relationships at fine and coarse spatial scales,respectively.Distinguishing between metrics that focus on different evolutionary depths is important,as different metrics can exhibit different scale-dependent patterns.展开更多
文摘Precision medicine aims to identify the right drug, for the right patient, at the right dose, at the right time, which is particularly important in cancer therapy. Problems such as the variability of treatment response and resistance to medication have been longstanding challenges in oncology, especially for development of new medications. Solid tumors, unlike hematologic malignancies or brain tumors, are remarkably diverse in their cellular origins and developmental timing. The ability of next-generation sequencing(NGS) to analyze the comprehensive landscape of genetic alterations brings promises to diseases that have a highly complex and heterogeneous genetic composition such as cancer. Here we provide an overview of how NGS is able to facilitate precision medicine and change the paradigm of cancer therapy, especially for solid tumors, through technical advancements, molecular diagnosis, response monitoring and clinical trials.
基金supported by the Australian Research Council Discovery Project(DP150103017)and an Australian Government Research Training Program(RTP)Scholarship.
文摘Aims Darwin’s naturalization hypothesis proposes that successfully established alien species are less closely related to native species due to differences in their ecological niches.Studies have provided support both for and against this hypothesis.One reason for this is the tendency for phylogenetic clustering between aliens and natives at broad spatial scales with overdispersion at fine scales.However,little is known about how the phylogenetic relatedness of alien species alters the phylogenetic structure of the communities they invade,and at which spatial scales effects may manifest.Here,we examine if invaded understorey plant communities,i.e.containing both native and alien taxa,are phylogenetically clustered or overdispersed,how relatedness changes with spatial scale and how aliens affect phylogenetic patterns in understorey communities.Methods Field surveys were conducted in dry forest understorey communities in south-east Australia at five spatial scales(1,20,500,1500 and 4500 m2).Standardized effect sizes of two metrics were used to quantify phylogenetic relatedness between communities and their alien and native subcommunities,and to examine how phylogenetic patterns change with spatial scale:(i)mean pairwise distance and(ii)mean nearest taxon distance(MNTD).Important Findings Aliens were closely related to each other,and this relatedness tended to increase with scale.Native species and the full community exhibited either no clear pattern of relatedness with increasing spatial scale or were no different from random.At intermediate spatial scales(20-500 m2),the whole community tended towards random whereas the natives were strongly overdispersed and the alien subcommunity strongly clustered.This suggests that invasion by closely related aliens shifts community phylogenetic structure from overdispersed towards random.Aliens and natives were distantly related across spatial scales,supporting Darwin’s naturalization hypothesis,but only when phylogenetic distance was quantified as MNTD.Phylogenetic dissimilarity between aliens and natives increased with spatial scale,counter to expected patterns.Our findings suggest that the strong phylogenetic clustering of aliens is driven by human-mediated introductions involving closely related taxa that can establish and spread successfully.Unexpected scale-dependent patterns of phylogenetic relatedness may result from stochastic processes such as fire and dispersal events and suggest that competition and habitat filtering do not exclusively dominate phylogenetic relationships at fine and coarse spatial scales,respectively.Distinguishing between metrics that focus on different evolutionary depths is important,as different metrics can exhibit different scale-dependent patterns.
