56 research outputs found

    When trees grow too long: Investigating the causes of highly inaccurate bayesian branch-length estimates

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    A surprising number of recent Bayesian phylogenetic analyses contain branch-length estimates that are several orders of magnitude longer than corresponding maximum-likelihood estimates. The levels of divergence implied by such branch lengths are unreasonable for studies using biological data and are known to be false for studies using simulated data. We conducted additional Bayesian analyses and studied approximate-posterior surfaces to investigate the causes underlying these large errors. We manipulated the starting parameter values of the Markov chain Monte Carlo (MCMC) analyses, the moves used by the MCMC analyses, and the prior-probability distribution on branch lengths. We demonstrate that inaccurate branch-length estimates result from either 1) poor mixing of MCMC chains or 2) posterior distributions with excessive weight at long tree lengths. Both effects are caused by a rapid increase in the volume of branch-length space as branches become longer. In the former case, both an MCMC move that scales all branch lengths in the tree simultaneously and the use of overdispersed starting branch lengths allow the chain to accurately sample the posterior distribution and should be used in Bayesian analyses of phylogeny. In the latter case, branch-length priors can have strong effects on resulting inferences and should be carefully chosen to reflect biological expectations. We provide a formula to calculate an exponential rate parameter for the branch-length prior that should eliminate inference of biased branch lengths in many cases. In any phylogenetic analysis, the biological plausibility of branch-length output must be carefully considered

    Genetic epidemiology of lymphatic filariasis in American Samoa after mass drug administration

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    Over 892 million people in 48 countries are at risk of infection by nematodes that cause lymphatic filariasis. As part of the Global Programme to Eliminate Lymphatic Filariasis, mass drug administration is distributed to communities until surveillance indicates infection rates are below target prevalence thresholds. In some countries, including American Samoa, lymphatic filariasis transmission persists despite years of mass drug administration and/or has resurged after cessation. Nothing is known about the population genetics of Wuchereria bancrofti worms in Polynesia, or whether local transmission is persisting and/or increasing due to inadequate mass drug administration coverage, expansion from residual hotspots, reintroduction from elsewhere, or a combination. We extracted DNA from microfilariae on blood slides collected during prevalence surveys in 2014 and 2016, comprising 31 pools of five microfilariae from 22 persons living in eight villages. We sequenced 1104 bp across three mitochondrial markers (ND4, COI, CYTB). We quantified parasite genetic differentiation using variant calls and estimated haplotypes using principal components analysis, F-statistics, and haplotype networks. Of the variants called, all but eight were shared across the main island of Tutuila, and three of those were from a previously described hotspot village, Fagali’i. Genotypic data did not support population genetic structure among regions or villages in 2016, although differences were observed between worms collected in Fagali’i in 2014 and those from 2016. Because estimated haplotype frequency varied between villages, these statistics suggested genetic differentiation, but were not consistent among villages. Finally, haplotype networks demonstrated American Samoan sequence clusters were related to previously published sequences from Papua New Guinea. These are, to our knowledge, the first reports of W. bancrofti genetic variation in Polynesia. The resurgent parasites circulating on the main island of American Samoa represent a single population. This study is the first step towards investigating how parasite population structure might inform strategies to manage resurgence and elimination of lymphatic filariasis

    Lymphatic filariasis epidemiology in Samoa in 2018: geographic clustering and higher antigen prevalence in older age groups

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    Background: Samoa conducted eight nationwide rounds of mass drug administration (MDA) for lymphatic filariasis (LF) between 1999 and 2011, and two targeted rounds in 2015 and 2017 in North West Upolu (NWU), one of three evaluation units (EUs). Transmission Assessment Surveys (TAS) were conducted in 2013 (failed in NWU) and 2017 (all three EUs failed). In 2018, Samoa was the first in the world to distribute nationwide triple-drug MDA using ivermectin, diethylcarbamazine, and albendazole. Surveillance and Monitoring to Eliminate LF and Scabies from Samoa (SaMELFS Samoa) is an operational research program designed to evaluate the effectiveness of triple-drug MDA on LF transmission and scabies prevalence in Samoa, and to compare the usefulness of different indicators of LF transmission. This paper reports results from the 2018 baseline survey and aims to i) investigate antigen (Ag) prevalence and spatial epidemiology, including geographic clustering; ii) compare Ag prevalence between two different age groups (5–9 years versus ≥10 years) as indicators of areas of ongoing transmission; and iii) assess the prevalence of limb lymphedema in those aged ≥15 years. Methods: A community-based cluster survey was conducted in 30 randomly selected and five purposively selected clusters (primary sampling units, PSUs), each comprising one or two villages. Participants were recruited through household surveys (age ≥5 years) and convenience surveys (age 5–9 years). Alere Filariasis Test Strips (FTS) were used to detect Ag, and prevalence was adjusted for survey design and standardized for age and gender. Adjusted Ag prevalence was estimated for each age group (5–9, ≥10, and all ages ≥5 years) for random and purposive PSUs, and by region. Intraclass correlation (ICC) was used to quantify clustering at regions, PSUs, and households. Results: A total of 3940 persons were included (1942 children aged 5–9 years, 1998 persons aged ≥10 years). Adjusted Ag prevalence in all ages ≥5 years in randomly and purposively selected PSUs were 4.0% (95% CI 2.8–5.6%) and 10.0% (95% CI 7.4–13.4%), respectively. In random PSUs, Ag prevalence was lower in those aged 5–9 years (1.3%, 95% CI 0.8–2.1%) than ≥10 years (4.7%, 95% CI 3.1–7.0%), and poorly correlated at the PSU level (R-square = 0.1459). Adjusted Ag prevalence in PSUs ranged from 0% to 10.3% (95% CI 5.9–17.6%) in randomly selected and 3.8% (95% CI 1.3–10.8%) to 20.0% (95% CI 15.3–25.8%) in purposively selected PSUs. ICC for Ag-positive individuals was higher at households (0.46) compared to PSUs (0.18) and regions (0.01). Conclusions: Our study confirmed ongoing transmission of LF in Samoa, in accordance with the 2017 TAS results. Ag prevalence varied significantly between PSUs, and there was poor correlation between prevalence in 5–9 year-olds and older ages, who had threefold higher prevalence. Sampling older age groups would provide more accurate estimates of overall prevalence, and be more sensitive for identifying residual hotspots. Higher prevalence in purposively selected PSUs shows local knowledge can help identify at least some hotspots

    <i>Strongyloides</i> questions-a research agenda for the future.

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    The Strongyloides genus of parasitic nematodes have a fascinating life cycle and biology, but are also important pathogens of people and a World Health Organization-defined neglected tropical disease. Here, a community of Strongyloides researchers have posed thirteen major questions about Strongyloides biology and infection that sets a Strongyloides research agenda for the future. This article is part of the Theo Murphy meeting issue 'Strongyloides: omics to worm-free populations'

    concatenatenexus_edMSR

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    This program is written by Shannon Hedtke, and takes all nexus files in a directory and concatenates them. I have modified the original script, which splits sequence names on "_" and removes all duplicates of the left hand side - something that is good for cleaning up among GenBank versions of the same sequence, but bad for removing allelles

    Targeted enrichment: maximizing orthologous gene comparisons across deep evolutionary time.

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    Estimated phylogenies of evolutionarily diverse taxa will be well supported and more likely to be historically accurate when the analysis contains large amounts of data-many genes sequenced across many taxa. Inferring such phylogenies for non-model organisms is challenging given limited resources for whole-genome sequencing. We take advantage of genomic data from a single species to test the limits of hybridization-based enrichment of hundreds of exons across frog species that diverged up to 250 million years ago. Enrichment success for a given species depends greatly on the divergence time between it and the reference species, and the resulting alignment contains a significant proportion of missing data. However, our alignment generates a well-supported phylogeny of frogs, suggesting that this technique is a practical solution towards resolving relationships across deep evolutionary time
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