Are skyline plot-based demographic estimates overly dependent on smoothing prior assumptions?

In Bayesian phylogenetics, the coalescent process provides an informative framework for inferring changes in the effective size of a population from a phylogeny (or tree) of sequences sampled from that population. Popular coalescent inference approaches such as the Bayesian Skyline Plot, Skyride and Skygrid all model these population size changes with a discontinuous, piecewise-constant function but then apply a smoothing prior to ensure that their posterior population size estimates transition gradually with time. These prior distributions implicitly encode extra population size information that is not available from the observed coalescent data i.e., the tree. Here we present a novel statistic, Ω, to quantify and disaggregate the relative contributions of the coalescent data and prior assumptions to the resulting posterior estimate precision. Our statistic also measures the additional mutual information introduced by such priors. Using Ω we show that, because it is surprisingly easy to over-parametrise piecewise-constant population models, common smoothing priors can lead to overconfident and potentially misleading inference, even under robust experimental designs. We propose Ω as a useful tool for detecting when effective population size estimates are overly reliant on prior assumptions and for improving quantification of the uncertainty in those estimates

Effects of neutralizing antibodies on escape from CD8+ T-cell responses in HIV-1 infection.

Despite substantial advances in our knowledge of immune responses against HIV-1 and of its evolution within the host, it remains unclear why control of the virus eventually breaks down. Here, we present a new theoretical framework for the infection dynamics of HIV-1 that combines antibody and CD8(+) T-cell responses, notably taking into account their different lifespans. Several apparent paradoxes in HIV pathogenesis and genetics of host susceptibility can be reconciled within this framework by assigning a crucial role to antibody responses in the control of viraemia. We argue that, although escape from or progressive loss of quality of CD8(+) T-cell responses can accelerate disease progression, the underlying cause of the breakdown of virus control is the loss of antibody induction due to depletion of CD4(+) T cells. Furthermore, strong antibody responses can prevent CD8(+) T-cell escape from occurring for an extended period, even in the presence of highly efficacious CD8(+) T-cell responses

稲垣足穂『少年愛の美学』の読書論的研究 --念者としての語り--

千葉大学大学院人文社会科学研究科研究プロジェクト報告書第144集 『パフォーマンスの民族誌的研究』橋本裕之

Exceptional Heterogeneity in Viral Evolutionary Dynamics Characterises Chronic Hepatitis C Virus Infection.

The treatment of HCV infection has seen significant progress, particularly since the approval of new direct-acting antiviral drugs. However these clinical achievements have been made despite an incomplete understanding of HCV replication and within-host evolution, especially compared with HIV-1. Here, we undertake a comprehensive analysis of HCV within-host evolution during chronic infection by investigating over 4000 viral sequences sampled longitudinally from 15 HCV-infected patients. We compare our HCV results to those from a well-studied HIV-1 cohort, revealing key differences in the evolutionary behaviour of these two chronic-infecting pathogens. Notably, we find an exceptional level of heterogeneity in the molecular evolution of HCV, both within and among infected individuals. Furthermore, these patterns are associated with the long-term maintenance of viral lineages within patients, which fluctuate in relative frequency in peripheral blood. Together, our findings demonstrate that HCV replication behavior is complex and likely comprises multiple viral subpopulations with distinct evolutionary dynamics. The presence of a structured viral population can explain apparent paradoxes in chronic HCV infection, such as rapid fluctuations in viral diversity and the reappearance of viral strains years after their initial detection.status: publishe

The Dawn of Open Access to Phylogenetic Data

The scientific enterprise depends critically on the preservation of and open access to published data. This basic tenet applies acutely to phylogenies (estimates of evolutionary relationships among species). Increasingly, phylogenies are estimated from increasingly large, genome-scale datasets using increasingly complex statistical methods that require increasing levels of expertise and computational investment. Moreover, the resulting phylogenetic data provide an explicit historical perspective that critically informs research in a vast and growing number of scientific disciplines. One such use is the study of changes in rates of lineage diversification (speciation - extinction) through time. As part of a meta-analysis in this area, we sought to collect phylogenetic data (comprising nucleotide sequence alignment and tree files) from 217 studies published in 46 journals over a 13-year period. We document our attempts to procure those data (from online archives and by direct request to corresponding authors), and report results of analyses (using Bayesian logistic regression) to assess the impact of various factors on the success of our efforts. Overall, complete phylogenetic data for ~60% of these studies are effectively lost to science. Our study indicates that phylogenetic data are more likely to be deposited in online archives and/or shared upon request when: (1) the publishing journal has a strong data-sharing policy; (2) the publishing journal has a higher impact factor, and; (3) the data are requested from faculty rather than students. Although the situation appears dire, our analyses suggest that it is far from hopeless: recent initiatives by the scientific community -- including policy changes by journals and funding agencies -- are improving the state of affairs

Exceptional Heterogeneity in Viral Evolutionary Dynamics Characterises Chronic Hepatitis C Virus Infection.

The treatment of HCV infection has seen significant progress, particularly since the approval of new direct-acting antiviral drugs. However these clinical achievements have been made despite an incomplete understanding of HCV replication and within-host evolution, especially compared with HIV-1. Here, we undertake a comprehensive analysis of HCV within-host evolution during chronic infection by investigating over 4000 viral sequences sampled longitudinally from 15 HCV-infected patients. We compare our HCV results to those from a well-studied HIV-1 cohort, revealing key differences in the evolutionary behaviour of these two chronic-infecting pathogens. Notably, we find an exceptional level of heterogeneity in the molecular evolution of HCV, both within and among infected individuals. Furthermore, these patterns are associated with the long-term maintenance of viral lineages within patients, which fluctuate in relative frequency in peripheral blood. Together, our findings demonstrate that HCV replication behavior is complex and likely comprises multiple viral subpopulations with distinct evolutionary dynamics. The presence of a structured viral population can explain apparent paradoxes in chronic HCV infection, such as rapid fluctuations in viral diversity and the reappearance of viral strains years after their initial detection.status: publishe

AS AVENTURAS DE DOG MENDONÇA E PIZZA BOY: UMA LEITURA

Na trilogia As Aventuras de Dog Mendonça e Pizza Boy (2010; 2011; 2013) e sua prequela (2012), Filipe Melo e Juan Cavia povoam Portugal, e em particular Lisboa, com vários corpos fantásticos: gárgulas, vampiros, lobisomens, zombies, demónios e outros seres habitam o universo lusitano naquela que é uma obra com claras referências cinematográficas aos mestres do cinema de horror e outros. Ao mesmo tempo, esta homenagem apresenta também uma reflexão sobre o corpo fantástico, a monstruosidade e o Outro. Centrando-se essencialmente nas figuras sobrenaturais desta obra, este ensaio aborda os corpos fantásticos presentes nesta BD, em particular o caso de Dog Mendonça, o lobisomem, e de Pazuul, o demónio em corpo de criança. Desta forma, o presente estudo tem um duplo objetivo: por um lado, explorar as influências fantásticas de As Aventuras de Dog Mendonça e Pizza Boy e, por outro, estabelecer uma leitura do corpo fantástico a partir da análise de duas personagens que circulam entre dois mundos numa mesma cidade, o mundo sobrenatural e o mundo humano

Reducing HIV infection in people who inject drugs is impossible without targeting recently-infected subjects.

Objective Although our understanding of viral transmission among people who inject drugs (PWID) has improved, we still know little about when and how many times each injector transmits HIV throughout the duration of infection. We describe HIV dynamics in PWID to evaluate which preventive strategies can be efficient. Design Due to the notably scarce interventions, HIV-1 spread explosively in Russia and Ukraine in 1990s. By studying this epidemic between 1995 and 2005, we characterized naturally occurring transmission dynamics of HIV among PWID. Method We combined publicly available HIV pol and env sequences with prevalence estimates from Russia and Ukraine under an evolutionary epidemiology framework to characterize HIV transmissibility between PWID. We then constructed compartmental models to simulate HIV spread among PWID. Results In the absence of interventions, each injector transmits on average to 10 others. Half of the transmissions take place within 1 month after primary infection, suggesting that the epidemic will expand even after blocking all the post–first month transmissions. Primary prevention can realistically target the first month of infection, and we show that it is very efficient to control the spread of HIV-1 in PWID. Treating acutely infected on top of primary prevention is notably effective. Conclusion As a large proportion of transmissions among PWID occur within 1 month after infection, reducing and delaying transmissions through scale-up of harm reduction programmes should always form the backbone of HIV control strategies in PWID.Growing PWID populations in the developing world,where primary prevention is scarce, constitutes a public health time bomb

Characterization of hepatitis C virus recombination in Cameroon by use of nonspecific next-generation sequencing.

The importance of recombination in the evolution and genetic diversity of the hepatitis C virus (HCV) is currently uncertain. Only a small number of intergenotypic recombinants have been identified so far, and each has core and envelope genes classified as belonging to genotype 2. Here, we investigated two putative genotype 4/1 recombinants from southern Cameroon using a number of approaches, including standard Sanger sequencing, genotype-specific PCR amplification, and non-HCV-specific Illumina RNA sequencing (RNA-seq). Recombination between genotypes 1 and 4 was confirmed in both samples, and the parental lineages of each recombinant belong to HCV subtypes that are cocirculating at a high prevalence in Cameroon. Using the RNA-seq approach, we obtained a complete genome for one sample, which contained a recombination breakpoint at the E2/P7 gene junction. We developed and applied a new method, called Deep SimPlot, which can be used to visualize and identify viral recombination directly from the short sequence reads created by next-generation sequencing in conjunction with a consensus sequence

A Possible Geographic Origin of Endemic Hepatitis C Virus 6a in Hong Kong: Evidences for the Association with Vietnamese Immigration

BACKGROUND: Hepatitis C virus (HCV) 6a accounts for 23.6% of all HCV infections of the general population and 58.5% of intravenous drug users in Hong Kong. However, the geographical origin of this highly predominant HCV subgenotype is largely unknown. This study explores a hypothesis for one possible transmission route of HCV 6a to Hong Kong. METHODS: NS5A sequences derived from 26 HCV 6a samples were chosen from a five year period (1999-2004) from epidemiologically unrelated patients from Hong Kong. Partial-NS5A sequences (513-bp from nt 6728 to 7240) were adopted for Bayesian coalescent analysis to reconstruct the evolutionary history of HCV infections in Hong Kong using the BEAST v1.3 program. A rooted phylogenetic tree was drawn for these sequences by alignment with reference Vietnamese sequences. Demographic data were accessed from "The Statistic Yearbooks of Hong Kong". RESULTS: Bayesian coalescent analysis showed that the rapid increase in 6a infections, which had increased more than 90-fold in Hong Kong from 1986 to 1994 correlated to two peaks of Vietnamese immigration to Hong Kong from 1978 to 1997. The second peak, which occurred from 1987 through 1997, overlapped with the rapid increase of HCV 6a occurrence in Hong Kong. Phylogenetic analyses have further revealed that HCV 6a strains from Vietnam may be ancestral to Hong Kong counterparts. CONCLUSIONS: The high predominance of HCV 6a infections in Hong Kong was possibly associated with Vietnamese immigration during 1987-1997