910 research outputs found
Circular Networks from Distorted Metrics
Trees have long been used as a graphical representation of species
relationships. However complex evolutionary events, such as genetic
reassortments or hybrid speciations which occur commonly in viruses, bacteria
and plants, do not fit into this elementary framework. Alternatively, various
network representations have been developed. Circular networks are a natural
generalization of leaf-labeled trees interpreted as split systems, that is,
collections of bipartitions over leaf labels corresponding to current species.
Although such networks do not explicitly model specific evolutionary events of
interest, their straightforward visualization and fast reconstruction have made
them a popular exploratory tool to detect network-like evolution in genetic
datasets.
Standard reconstruction methods for circular networks, such as Neighbor-Net,
rely on an associated metric on the species set. Such a metric is first
estimated from DNA sequences, which leads to a key difficulty: distantly
related sequences produce statistically unreliable estimates. This is
problematic for Neighbor-Net as it is based on the popular tree reconstruction
method Neighbor-Joining, whose sensitivity to distance estimation errors is
well established theoretically. In the tree case, more robust reconstruction
methods have been developed using the notion of a distorted metric, which
captures the dependence of the error in the distance through a radius of
accuracy. Here we design the first circular network reconstruction method based
on distorted metrics. Our method is computationally efficient. Moreover, the
analysis of its radius of accuracy highlights the important role played by the
maximum incompatibility, a measure of the extent to which the network differs
from a tree.Comment: Submitte
A Note on Encodings of Phylogenetic Networks of Bounded Level
Driven by the need for better models that allow one to shed light into the
question how life's diversity has evolved, phylogenetic networks have now
joined phylogenetic trees in the center of phylogenetics research. Like
phylogenetic trees, such networks canonically induce collections of
phylogenetic trees, clusters, and triplets, respectively. Thus it is not
surprising that many network approaches aim to reconstruct a phylogenetic
network from such collections. Related to the well-studied perfect phylogeny
problem, the following question is of fundamental importance in this context:
When does one of the above collections encode (i.e. uniquely describe) the
network that induces it? In this note, we present a complete answer to this
question for the special case of a level-1 (phylogenetic) network by
characterizing those level-1 networks for which an encoding in terms of one (or
equivalently all) of the above collections exists. Given that this type of
network forms the first layer of the rich hierarchy of level-k networks, k a
non-negative integer, it is natural to wonder whether our arguments could be
extended to members of that hierarchy for higher values for k. By giving
examples, we show that this is not the case
Functional significance may underlie the taxonomic utility of single amino acid substitutions in conserved proteins
We hypothesized that some amino acid substitutions in conserved proteins that are strongly fixed by critical functional roles would show lineage-specific distributions. As an example of an archetypal conserved eukaryotic protein we considered the active site of ß-tubulin. Our analysis identified one amino acid substitution—ß-tubulin F224—which was highly lineage specific. Investigation of ß-tubulin for other phylogenetically restricted amino acids identified several with apparent specificity for well-defined phylogenetic groups. Intriguingly, none showed specificity for “supergroups” other than the unikonts. To understand why, we analysed the ß-tubulin Neighbor-Net and demonstrated a fundamental division between core ß-tubulins (plant-like) and divergent ß-tubulins (animal and fungal). F224 was almost completely restricted to the core ß-tubulins, while divergent ß-tubulins possessed Y224. Thus, our specific example offers insight into the restrictions associated with the co-evolution of ß-tubulin during the radiation of eukaryotes, underlining a fundamental dichotomy between F-type, core ß-tubulins and Y-type, divergent ß-tubulins. More broadly our study provides proof of principle for the taxonomic utility of critical amino acids in the active sites of conserved proteins
Re-examination of the Controversial Coexistence of Traumatic Brain Injury and Posttraumatic Stress Disorder: Misdiagnosis and Self-Report Measures
The coexistence of traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) remains a controversial issue in the literature. To address this controversy, we focused primarily on the civilian-related literature of TBI and PTSD. Some investigators have argued that individuals who had been rendered unconscious or suffered amnesia due to a TBI are unable to develop PTSD because they would be unable to consciously experience the symptoms of fear, helplessness, and horror associated with the development of PTSD. Other investigators have reported that individuals who sustain TBI, regardless of its severity, can develop PTSD even in the context of prolonged unconsciousness. A careful review of the methodologies employed in these studies reveals that investigators who relied on clinical interviews of TBI patients to diagnose PTSD found little or no evidence of PTSD. In contrast, investigators who relied on PTSD questionnaires to diagnose PTSD found considerable evidence of PTSD. Further analysis revealed that many of the TBI patients who were initially diagnosed with PTSD according to self-report questionnaires did not meet the diagnostic criteria for PTSD upon completion of a clinical interview. In particular, patients with severe TBI were often misdiagnosed with PTSD. A number of investigators found that many of the severe TBI patients failed to follow the questionnaire instructions and erroneously endorsed PTSD symptoms because of their cognitive difficulties. Because PTSD questionnaires are not designed to discriminate between PTSD and TBI symptoms or determine whether a patient's responses are accurate or exaggerated, studies that rely on self-report questionnaires to evaluate PTSD in TBI patients are at risk of misdiagnosing PTSD. Further research should evaluate the degree to which misdiagnosis of PTSD occurs in individuals who have sustained mild TBI
Differential Dynamics of Transposable Elements during Long-Term Diploidization of Nicotiana Section Repandae (Solanaceae) Allopolyploid Genomes
PubMed ID: 23185607This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
The genome sequence of <i>Trypanosoma brucei gambiense</i>, causative agent of chronic Human African Trypanosomiasis
<p><b>Background:</b> <i>Trypanosoma brucei gambiense</i> is the causative agent of chronic Human African Trypanosomiasis or sleeping sickness, a disease endemic across often poor and rural areas of Western and Central Africa. We have previously published the genome sequence of a <i>T. b. brucei</i> isolate, and have now employed a comparative genomics approach to understand the scale of genomic variation between <i>T. b. gambiense</i> and the reference genome. We sought to identify features that were uniquely associated with <i>T. b. gambiense</i> and its ability to infect humans.</p>
<p><b>Methods and findings:</b> An improved high-quality draft genome sequence for the group 1 <i>T. b. gambiense</i> DAL 972 isolate was produced using a whole-genome shotgun strategy. Comparison with <i>T. b. brucei</i> showed that sequence identity averages 99.2% in coding regions, and gene order is largely collinear. However, variation associated with segmental duplications and tandem gene arrays suggests some reduction of functional repertoire in <i>T. b. gambiense</i> DAL 972. A comparison of the variant surface glycoproteins (VSG) in <i>T. b. brucei</i> with all <i>T. b. gambiense</i> sequence reads showed that the essential structural repertoire of VSG domains is conserved across <i>T. brucei</i>.</p>
<p><b>Conclusions:</b> This study provides the first estimate of intraspecific genomic variation within <i>T. brucei</i>, and so has important consequences for future population genomics studies. We have shown that the <i>T. b. gambiense</i> genome corresponds closely with the reference, which should therefore be an effective scaffold for any <i>T. brucei</i> genome sequence data. As VSG repertoire is also well conserved, it may be feasible to describe the total diversity of variant antigens. While we describe several as yet uncharacterized gene families with predicted cell surface roles that were expanded in number in <i>T. b. brucei</i>, no <i>T. b. gambiense</i>-specific gene was identified outside of the subtelomeres that could explain the ability to infect humans.</p>
Phylogenomics of non-model ciliates based on transcriptomic analyses
© The Author(s) 2015. This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited. The attached file is the published version of the article
Combinatorial Clustering of Residue Position Subsets Predicts Inhibitor Affinity across the Human Kinome
The protein kinases are a large family of enzymes that play fundamental roles in propagating signals within the cell. Because
of the high degree of binding site similarity shared among protein kinases, designing drug compounds with high specificity
among the kinases has proven difficult. However, computational approaches to comparing the 3-dimensional geometry and
physicochemical properties of key binding site residue positions have been shown to be informative of inhibitor selectivity.
The Combinatorial Clustering Of Residue Position Subsets (CCORPS) method, introduced here, provides a semi-supervised
learning approach for identifying structural features that are correlated with a given set of annotation labels. Here, CCORPS is
applied to the problem of identifying structural features of the kinase ATP binding site that are informative of inhibitor
binding. CCORPS is demonstrated to make perfect or near-perfect predictions for the binding affinity profile of 8 of the 38
kinase inhibitors studied, while only having overall poor predictive ability for 1 of the 38 compounds. Additionally, CCORPS is
shown to identify shared structural features across phylogenetically diverse groups of kinases that are correlated with
binding affinity for particular inhibitors; such instances of structural similarity among phylogenetically diverse kinases are
also shown to not be rare among kinases. Finally, these function-specific structural features may serve as potential starting
points for the development of highly specific kinase inhibitors
Phylogenomics: Gene Duplication, Unrecognized Paralogy and Outgroup Choice
Comparative genomics has revealed the ubiquity of gene and genome duplication and subsequent gene loss. In the case of gene duplication and subsequent loss, gene trees can differ from species trees, thus frequent gene duplication poses a challenge for reconstruction of species relationships. Here I address the case of multi-gene sets of putative orthologs that include some unrecognized paralogs due to ancestral gene duplication, and ask how outgroups should best be chosen to reduce the degree of non-species tree (NST) signal. Consideration of expected internal branch lengths supports several conclusions: (i) when a single outgroup is used, the degree of NST signal arising from gene duplication is either independent of outgroup choice, or is minimized by use of a maximally closely related post-duplication (MCRPD) outgroup; (ii) when two outgroups are used, NST signal is minimized by using one MCRPD outgroup, while the position of the second outgroup is of lesser importance; and (iii) when two outgroups are used, the ability to detect gene trees that are inconsistent with known aspects of the species tree is maximized by use of one MCRPD, and is either independent of the position of the second outgroup, or is maximized for a more distantly related second outgroup. Overall, these results generalize the utility of closely-related outgroups for phylogenetic analysis
Association of food security status with overweight and dietary intake: exploration of White British and Pakistani-origin families in the Born in Bradford cohort.
BACKGROUND: Food insecurity has been associated with dietary intake and weight status in UK adults and children although results have been mixed and ethnicity has not been explored. We aimed to compare prevalence and trajectories of weight and dietary intakes among food secure and insecure White British and Pakistani-origin families. METHODS: At 12 months postpartum, mothers in the Born in Bradford cohort completed a questionnaire on food security status and a food frequency questionnaire (FFQ) assessing their child's intake in the previous month; at 18 months postpartum, mothers completed a short-form FFQ assessing dietary intake in the previous 12 months. Weights and heights of mothers and infants were assessed at 12-, 24-, and 36-months postpartum, with an additional measurement of children taken at 4-5 years. Associations between food security status and dietary intakes were assessed using Wilcoxon-Mann-Whitney for continuous variables and χ2 or Fisher's exact tests for categorical variables. Quantile and logistic regression were used to determine dietary intakes adjusting for mother's age. Linear mixed effects models were used to assess longitudinal changes in body mass index (BMI) in mothers and BMI z-scores in children. RESULTS: At 12 months postpartum, White British mothers reported more food insecurity than Pakistani-origin mothers (11% vs 7%; p < 0.01) and more food insecure mothers were overweight. Between 12 and 36 months postpartum, BMI increased more among food insecure Pakistani-origin mothers (β = 0.77 units, [95% Confidence Interval [CI]: 0.40, 1.10]) than food secure (β = 0.44 units, 95% CI: 0.33, 0.55). This was also found in Pakistani-origin children (BMI z-score: food insecure β = 0.40 units, 95% CI: 0.22, 0.59; food secure β = 0.25 units, 95% CI: 0.20, 0.29). No significant increases in BMI were observed for food secure or insecure White British mothers while BMI z-score increased by 0.17 (95% CI: 0.13, 0.21) for food secure White British children. Food insecure mothers and children had dietary intakes of poorer quality, with fewer vegetables and higher consumption of sugar-sweetened drinks. CONCLUSIONS: Food security status is associated with body weight and dietary intakes differentially by ethnicity. These are important considerations for developing targeted interventions
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