241 research outputs found
Minimizing the average distance to a closest leaf in a phylogenetic tree
When performing an analysis on a collection of molecular sequences, it can be
convenient to reduce the number of sequences under consideration while
maintaining some characteristic of a larger collection of sequences. For
example, one may wish to select a subset of high-quality sequences that
represent the diversity of a larger collection of sequences. One may also wish
to specialize a large database of characterized "reference sequences" to a
smaller subset that is as close as possible on average to a collection of
"query sequences" of interest. Such a representative subset can be useful
whenever one wishes to find a set of reference sequences that is appropriate to
use for comparative analysis of environmentally-derived sequences, such as for
selecting "reference tree" sequences for phylogenetic placement of metagenomic
reads. In this paper we formalize these problems in terms of the minimization
of the Average Distance to the Closest Leaf (ADCL) and investigate algorithms
to perform the relevant minimization. We show that the greedy algorithm is not
effective, show that a variant of the Partitioning Among Medoids (PAM)
heuristic gets stuck in local minima, and develop an exact dynamic programming
approach. Using this exact program we note that the performance of PAM appears
to be good for simulated trees, and is faster than the exact algorithm for
small trees. On the other hand, the exact program gives solutions for all
numbers of leaves less than or equal to the given desired number of leaves,
while PAM only gives a solution for the pre-specified number of leaves. Via
application to real data, we show that the ADCL criterion chooses chimeric
sequences less often than random subsets, while the maximization of
phylogenetic diversity chooses them more often than random. These algorithms
have been implemented in publicly available software.Comment: Please contact us with any comments or questions
Abundance-weighted phylogenetic diversity measures distinguish microbial community states and are robust to sampling depth
In microbial ecology studies, the most commonly used ways of investigating
alpha (within-sample) diversity are either to apply count-only measures such as
Simpson's index to Operational Taxonomic Unit (OTU) groupings, or to use
classical phylogenetic diversity (PD), which is not abundance-weighted.
Although alpha diversity measures that use abundance information in a
phylogenetic framework do exist, but are not widely used within the microbial
ecology community. The performance of abundance-weighted phylogenetic diversity
measures compared to classical discrete measures has not been explored, and the
behavior of these measures under rarefaction (sub-sampling) is not yet clear.
In this paper we compare the ability of various alpha diversity measures to
distinguish between different community states in the human microbiome for
three different data sets. We also present and compare a novel one-parameter
family of alpha diversity measures, BWPD_\theta, that interpolates between
classical phylogenetic diversity (PD) and an abundance-weighted extension of
PD. Additionally, we examine the sensitivity of these phylogenetic diversity
measures to sampling, via computational experiments and by deriving a closed
form solution for the expectation of phylogenetic quadratic entropy under
re-sampling. In all three of the datasets considered, an abundance-weighted
measure is the best differentiator between community states. OTU-based
measures, on the other hand, are less effective in distinguishing community
types. In addition, abundance-weighted phylogenetic diversity measures are less
sensitive to differing sampling intensity than their unweighted counterparts.
Based on these results we encourage the use of abundance-weighted phylogenetic
diversity measures, especially for cases such as microbial ecology where
species delimitation is difficult.Comment: Submitted to Peer
Quantifying evolutionary constraints on B cell affinity maturation
The antibody repertoire of each individual is continuously updated by the
evolutionary process of B cell receptor mutation and selection. It has recently
become possible to gain detailed information concerning this process through
high-throughput sequencing. Here, we develop modern statistical molecular
evolution methods for the analysis of B cell sequence data, and then apply them
to a very deep short-read data set of B cell receptors. We find that the
substitution process is conserved across individuals but varies significantly
across gene segments. We investigate selection on B cell receptors using a
novel method that side-steps the difficulties encountered by previous work in
differentiating between selection and motif-driven mutation; this is done
through stochastic mapping and empirical Bayes estimators that compare the
evolution of in-frame and out-of-frame rearrangements. We use this new method
to derive a per-residue map of selection, which provides a more nuanced view of
the constraints on framework and variable regions.Comment: Previously entitled "Substitution and site-specific selection driving
B cell affinity maturation is consistent across individuals
Modular invariance, lattice field theories and finite size corrections
We give a lattice theory treatment of certain one and two dimensional quantum
field theories. In one dimension we construct a combinatorial version of a
non-trivial field theory on the circle which is of some independent interest in
itself while in two dimensions we consider a field theory on a toroidal
triangular lattice. We take a continuous spin Gaussian model on a toroidal
triangular lattice with periods and where the spins carry a
representation of the fundamental group of the torus labeled by phases
and . We compute the {\it exact finite size and lattice corrections}, to
the partition function , for arbitrary mass and phases . Summing
over a specified set of phases gives the corresponding result for
the Ising model on a torus. An interesting property of the model is that the
limits and do not commute. Also when
the model exhibits a {\it vortex critical phase} when at least one of the
is non-zero. In the continuum or scaling limit, for arbitrary , the finite
size corrections to are {\it modular invariant} and for the critical
phase are given by elliptic theta functions. In the cylinder limit
the ``cylinder charge'' is a
non-monotonic function of that ranges from for to
zero for but from which one can determine the central
charge . The study of the continuum limit of these field theories provides a
kind of quantum theoretic analog of the link between certain combinatorial and
analytic topological quantities.Comment: 25 pages Plain Te
Phylogenomic Analysis Reveals Dynamic Evolutionary History of the Drosophila Heterochromatin Protein 1 (HP1) Gene Family
Heterochromatin is the gene-poor, satellite-rich eukaryotic genome compartment that supports many essential cellular processes. The functional diversity of proteins that bind and often epigenetically define heterochromatic DNA sequence reflects the diverse functions supported by this enigmatic genome compartment. Moreover, heterogeneous signatures of selection at chromosomal proteins often mirror the heterogeneity of evolutionary forces that act on heterochromatic DNA. To identify new such surrogates for dissecting heterochromatin function and evolution, we conducted a comprehensive phylogenomic analysis of the Heterochromatin Protein 1 gene family across 40 million years of Drosophila evolution. Our study expands this gene family from 5 genes to at least 26 genes, including several uncharacterized genes in Drosophila melanogaster. The 21 newly defined HP1s introduce unprecedented structural diversity, lineage-restriction, and germline-biased expression patterns into the HP1 family. We find little evidence of positive selection at these HP1 genes in both population genetic and molecular evolution analyses. Instead, we find that dynamic evolution occurs via prolific gene gains and losses. Despite this dynamic gene turnover, the number of HP1 genes is relatively constant across species. We propose that karyotype evolution drives at least some HP1 gene turnover. For example, the loss of the male germline-restricted HP1E in the obscura group coincides with one episode of dramatic karyotypic evolution, including the gain of a neo-Y in this lineage. This expanded compendium of ovary- and testis-restricted HP1 genes revealed by our study, together with correlated gain/loss dynamics and chromosome fission/fusion events, will guide functional analyses of novel roles supported by germline chromatin
The human microbiome in Barrett’s esophagus is hard to stomach
The incidence of esophageal adenocarcinoma (EAC) has increased nearly five-fold over the last four decades in the United States. Barrett's esophagus, the replacement of the normal squamous epithelial lining with a mucus-secreting columnar epithelium, is the only known precursor to EAC. Like other parts of the gastrointestinal (GI) tract, the esophagus hosts a variety of bacteria and comparisons among published studies suggest bacterial communities in the stomach and esophagus differ. Chronic infection with Helicobacter pylori in the stomach has been inversely associated with development of EAC, but the mechanisms underlying this association remain unclear.The bacterial composition in the upper GI tract was characterized in a subset of participants (n=12) of the Seattle Barrett's Esophagus Research cohort using broad-range 16S PCR and pyrosequencing of biopsy and brush samples collected from squamous esophagus, Barrett's esophagus, stomach corpus and stomach antrum. Three of the individuals were sampled at two separate time points. Prevalence of H. pylori infection and subsequent development of aneuploidy (n=339) and EAC (n=433) was examined in a larger subset of this cohort.Within individuals, bacterial communities of the stomach and esophagus showed overlapping community membership. Despite closer proximity, the stomach antrum and corpus communities were less similar than the antrum and esophageal samples. Re-sampling of study participants revealed similar upper GI community membership in two of three cases. In this Barrett's esophagus cohort, Streptococcus and Prevotella species dominate the upper GI and the ratio of these two species is associated with waist-to-hip ratio and hiatal hernia length, two known EAC risk factors in Barrett's esophagus. H. pylori-positive individuals had a significantly decreased incidence of aneuploidy and a non-significant trend toward lower incidence of EAC
Bacterial Communities in Women with Bacterial Vaginosis: High Resolution Phylogenetic Analyses Reveal Relationships of Microbiota to Clinical Criteria
Bacterial vaginosis (BV) is a common condition that is associated with numerous adverse health outcomes and is characterized by poorly understood changes in the vaginal microbiota. We sought to describe the composition and diversity of the vaginal bacterial biota in women with BV using deep sequencing of the 16S rRNA gene coupled with species-level taxonomic identification. We investigated the associations between the presence of individual bacterial species and clinical diagnostic characteristics of BV.Broad-range 16S rRNA gene PCR and pyrosequencing were performed on vaginal swabs from 220 women with and without BV. BV was assessed by Amsel's clinical criteria and confirmed by Gram stain. Taxonomic classification was performed using phylogenetic placement tools that assigned 99% of query sequence reads to the species level. Women with BV had heterogeneous vaginal bacterial communities that were usually not dominated by a single taxon. In the absence of BV, vaginal bacterial communities were dominated by either Lactobacillus crispatus or Lactobacillus iners. Leptotrichia amnionii and Eggerthella sp. were the only two BV-associated bacteria (BVABs) significantly associated with each of the four Amsel's criteria. Co-occurrence analysis revealed the presence of several sub-groups of BVABs suggesting metabolic co-dependencies. Greater abundance of several BVABs was observed in Black women without BV.The human vaginal bacterial biota is heterogeneous and marked by greater species richness and diversity in women with BV; no species is universally present. Different bacterial species have different associations with the four clinical criteria, which may account for discrepancies often observed between Amsel and Nugent (Gram stain) diagnostic criteria. Several BVABs exhibited race-dependent prevalence when analyzed in separate groups by BV status which may contribute to increased incidence of BV in Black women. Tools developed in this project can be used to study microbial ecology in diverse settings at high resolution
Vaccine innovation, translational research and the management of knowledge accumulation
What does it take to translate research into socially beneficial technologies like vaccines? Current policy that focuses on expanding research or strengthening incentives overlooks how the supply and demand of innovation is mediated by problem-solving processes that generate knowledge which is often fragmented and only locally valid. This paper details some of the conditions that allow fragmented, local knowledge to accumulate through a series of structured steps from the artificial simplicity of the laboratory to the complexity of real world application. Poliomyelitis is used as an illustrative case to highlight the importance of experimental animal models and the extent of co-ordination that can be required if they are missing. Implications for the governance and management of current attempts to produce vaccines for HIV, TB and Malaria are discussed.
Article Outlin
Attitudes and perceptions of pregnant women towards the use of Anti-Retroviral Therapy in Nigeria
Background
Mother-to-child transmission of Human Immunodeficiency Virus continues to be a major problem in Nigeria. Despite several initiatives, the number of infected pregnant women receiving Anti-Retroviral Therapy to prevent Mother-to-child transmission of the virus remains low in Nigeria. Evidence suggests that attitudes and perceptions of the pregnant women influence their use of Anti-Retroviral Therapy.
Aim
To understand the attitudes and perceptions of Human Immunodeficiency Virus infected pregnant women towards the use of Anti-Retroviral Therapy for prevention of mother-to-child transmission in Nigeria.
Method
Twenty four Human Immunodeficiency Virus infected pregnant women were purposively selected from antenatal clinics. Women’s attitudes and perceptions towards the use of Anti-Retroviral Therapy were explored using semi-structured in-depth interviews conducted in May/June 2016. All interviews were recorded, transcribed and analysed using thematic approach.
Findings
Overall, participants reflected a positive attitude about using Anti-Retroviral Therapy to prevent mother-to-child transmission and perceived the treatment as beneficial. The main themes identified included: perceived benefits of Anti-Retroviral Therapy; barriers to using Anti-Retroviral Therapy; threat from the susceptibility to the illness and the severity; perceived roles in treatment; and the negative behaviours of healthcare providers.
Conclusion
The findings provide useful insights to inform Nigeria’s health policies on Anti-Retroviral Therapy. There is a need to educate the women on the benefits of the treatment as well as how they can cope with side effects and the daily regimen of the therapy during pregnancy. The findings also indicate the need for training healthcare providers on facilitative patient-provider relationship
- …