50 research outputs found
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
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
Structural Analysis of the Essential Resuscitation Promoting Factor YeaZ Suggests a Mechanism of Nucleotide Regulation through Dimer Reorganization
Extent: 8p.Background: The yeaZ gene product forms part of the conserved network YjeE/YeaZ/YgjD essential for the survival of many Gram-negative eubacteria. Among other as yet unidentified roles, YeaZ functions as a resuscitation promoting factor required for survival and resuscitation of cells in a viable but non-culturable (VBNC) state. Methodology/Principal Findings: In order to investigate in detail the structure/function relationship of this family of proteins we have performed X-ray crystallographic studies of Vibrio parahaemolyticus YeaZ. The YeaZ structure showed that it has a classic actin-like nucleotide-binding fold. Comparisons of this crystal structure to that of available homologues from E. coli, T. maritima and S. typhimurium revealed two distinctly different modes of dimer formation. In one form, prevalent in the absence of nucleotide, the putative nucleotide-binding site is incomplete, lacking a binding pocket for a nucleotide base. In the second form, residues from the second subunit complete the nucleotide-binding site. This suggests that the two dimer architectures observed in the crystal structures correspond to a free and a nucleotide-bound form of YeaZ. A multiple sequence alignment of YeaZ proteins from different bacteria allowed us to identify a large conserved hydrophobic patch on the protein surface that becomes exposed upon nucleotide-driven dimer re-arrangement. We hypothesize that the transition between two dimer architectures represents the transition between the ‘on’ and ‘off’ states of YeaZ. The effect of this transition is to alternately expose and bury a docking site for the partner protein YgjD. Conclusions/Significance: This paper provides the first structural insight into the putative mechanism of nucleotide regulation of YeaZ through dimer reorganization. Our analysis suggests that nucleotide binding to YeaZ may act as a regulator or switch that changes YeaZ shape, allowing it to switch partners between YjeE and YgjD.Inci Aydin, Yumiko Saijo-Hamano, Keiichi Namba, Connor Thomas and Anna Roujeinikov
The James Webb Space Telescope Mission
Twenty-six years ago a small committee report, building on earlier studies,
expounded a compelling and poetic vision for the future of astronomy, calling
for an infrared-optimized space telescope with an aperture of at least .
With the support of their governments in the US, Europe, and Canada, 20,000
people realized that vision as the James Webb Space Telescope. A
generation of astronomers will celebrate their accomplishments for the life of
the mission, potentially as long as 20 years, and beyond. This report and the
scientific discoveries that follow are extended thank-you notes to the 20,000
team members. The telescope is working perfectly, with much better image
quality than expected. In this and accompanying papers, we give a brief
history, describe the observatory, outline its objectives and current observing
program, and discuss the inventions and people who made it possible. We cite
detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space
Telescope Overview, 29 pages, 4 figure
Recommended from our members
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 (BCR) 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 dataset of BCRs. We find that the substitution process is conserved across individuals but varies significantly across gene segments. We investigate selection on BCRs 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