70 research outputs found
A unified data representation theory for network visualization, ordering and coarse-graining
Representation of large data sets became a key question of many scientific
disciplines in the last decade. Several approaches for network visualization,
data ordering and coarse-graining accomplished this goal. However, there was no
underlying theoretical framework linking these problems. Here we show an
elegant, information theoretic data representation approach as a unified
solution of network visualization, data ordering and coarse-graining. The
optimal representation is the hardest to distinguish from the original data
matrix, measured by the relative entropy. The representation of network nodes
as probability distributions provides an efficient visualization method and, in
one dimension, an ordering of network nodes and edges. Coarse-grained
representations of the input network enable both efficient data compression and
hierarchical visualization to achieve high quality representations of larger
data sets. Our unified data representation theory will help the analysis of
extensive data sets, by revealing the large-scale structure of complex networks
in a comprehensible form.Comment: 13 pages, 5 figure
Identifying metabolite markers for preterm birth in cervicovaginal fluid by magnetic resonance spectroscopy
Introduction Preterm birth (PTB) may be preceded by
changes in the vaginal microflora and metabolite profiles.
Objectives We sought to characterise the metabolite
profile of cervicovaginal fluid (CVF) of pregnant women
by 1H NMR spectroscopy, and assess their predictive value
for PTB.
Methods A pair of high-vaginal swabs was obtained from
pregnant women with no evidence of clinical infection and
grouped as follows: asymptomatic low risk (ALR) women
with no previous history of PTB, assessed at 20–22 gestational
weeks, g.w., n = 83; asymptomatic high risk
(AHR) women with a previous history of PTB, assessed at
both 20–22 g.w., n = 71, and 26–28 g.w., n = 58; and
women presenting with symptoms of preterm labor (PTL)
(SYM), assessed at 24–36 g.w., n = 65. Vaginal secretions
were dissolved in phosphate buffered saline and scanned
with a 9.4 T NMR spectrometer.
Results Six metabolites (lactate, alanine, acetate, glutamine/glutamate,
succinate and glucose) were analysed. In
all study cohorts vaginal pH correlated with lactate integral
(r = -0.62, p\0.0001). Lactate integrals were higher in
the term ALR compared to the AHR (20–22 g.w.) women
(p = 0.003). Acetate integrals were higher in the preterm
versus term women for the AHR (20–22 g.w.) (p = 0.048)
and SYM (p = 0.003) groups; and was predictive of
PTB\37 g.w. (AUC 0.78; 95 % CI 0.61–0.95), and
delivery within 2 weeks of the index assessment (AUC
0.84; 95 % CI 0.64–1) in the SYM women, whilst other
metabolites were not.
Conclusion High CVF acetate integral of women with
symptoms of PTL appears predictive of preterm delivery,
as well as delivery within 2 weeks of presentation
Human Population Differentiation Is Strongly Correlated with Local Recombination Rate
Allele frequency differences across populations can provide valuable information both for studying population structure and for identifying loci that have been targets of natural selection. Here, we examine the relationship between recombination rate and population differentiation in humans by analyzing two uniformly-ascertained, whole-genome data sets. We find that population differentiation as assessed by inter-continental FST shows negative correlation with recombination rate, with FST reduced by 10% in the tenth of the genome with the highest recombination rate compared with the tenth of the genome with the lowest recombination rate (P≪10−12). This pattern cannot be explained by the mutagenic properties of recombination and instead must reflect the impact of selection in the last 100,000 years since human continental populations split. The correlation between recombination rate and FST has a qualitatively different relationship for FST between African and non-African populations and for FST between European and East Asian populations, suggesting varying levels or types of selection in different epochs of human history
Pervasive Hitchhiking at Coding and Regulatory Sites in Humans
Much effort and interest have focused on assessing the importance of natural
selection, particularly positive natural selection, in shaping the human genome.
Although scans for positive selection have identified candidate loci that may be
associated with positive selection in humans, such scans do not indicate whether
adaptation is frequent in general in humans. Studies based on the reasoning of
the MacDonald–Kreitman test, which, in principle, can be used to
evaluate the extent of positive selection, suggested that adaptation is
detectable in the human genome but that it is less common than in Drosophila or
Escherichia coli. Both positive and purifying natural
selection at functional sites should affect levels and patterns of polymorphism
at linked nonfunctional sites. Here, we search for these effects by analyzing
patterns of neutral polymorphism in humans in relation to the rates of
recombination, functional density, and functional divergence with chimpanzees.
We find that the levels of neutral polymorphism are lower in the regions of
lower recombination and in the regions of higher functional density or
divergence. These correlations persist after controlling for the variation in GC
content, density of simple repeats, selective constraint, mutation rate, and
depth of sequencing coverage. We argue that these results are most plausibly
explained by the effects of natural selection at functional
sites—either recurrent selective sweeps or background
selection—on the levels of linked neutral polymorphism. Natural
selection at both coding and regulatory sites appears to affect linked neutral
polymorphism, reducing neutral polymorphism by 6% genome-wide and by
11% in the gene-rich half of the human genome. These findings suggest
that the effects of natural selection at linked sites cannot be ignored in the
study of neutral human polymorphism
The vaginal microbiota associates with the regression of untreated cervical intraepithelial neoplasia 2 lesions
Emerging evidence suggests associations between the vaginal microbiota (VMB) composition, human papillomavirus (HPV) infection, and cervical intraepithelial neoplasia (CIN); however, causal inference remains uncertain. Here, we use bacterial DNA sequencing from serially collected vaginal samples from a cohort of 87 adolescent and young women aged 16–26 years with histologically confirmed, untreated CIN2 lesions to determine whether VMB composition affects rates of regression over 24 months. We show that women with a Lactobacillus-dominant microbiome at baseline are more likely to have regressive disease at 12 months. Lactobacillus spp. depletion and presence of specific anaerobic taxa including Megasphaera, Prevotella timonensis and Gardnerella vaginalis are associated with CIN2 persistence and slower regression. These findings suggest that VMB composition may be a future useful biomarker in predicting disease outcome and tailoring surveillance, whilst it may offer rational targets for the development of new prevention and treatment strategies
Comparison of Storage Conditions for Human Vaginal Microbiome Studies
BACKGROUND: The effect of storage conditions on the microbiome and metabolite composition of human biological samples has not been thoroughly investigated as a potential source of bias. We evaluated the effect of two common storage conditions used in clinical trials on the bacterial and metabolite composition of the vaginal microbiota using pyrosequencing of barcoded 16S rRNA gene sequencing and (1)H-NMR analyses. METHODOLOGY/PRINCIPAL FINDINGS: Eight women were enrolled and four mid-vaginal swabs were collected by a physician from each woman. The samples were either processed immediately, stored at -80°C for 4 weeks or at -20°C for 1 week followed by transfer to -80°C for another 4 weeks prior to analysis. Statistical methods, including Kolmogorovo-Smirnov and Wilcoxon tests, were performed to evaluate the differences in vaginal bacterial community composition and metabolites between samples stored under different conditions. The results showed that there were no significant differences between samples processed immediately after collection or stored for varying durations. (1)H-NMR analysis of the small molecule metabolites in vaginal secretions indicated that high levels of lactic acid were associated with Lactobacillus-dominated communities. Relative abundance of lactic acid did not appear to correlate with relative abundance of individual Lactobacillus sp. in this limited sample, although lower levels of lactic acid were observed when L. gasseri was dominant, indicating differences in metabolic output of seemingly similar communities. CONCLUSIONS/SIGNIFICANCE: These findings benefit large-scale, field-based microbiome and metabolomic studies of the vaginal microbiota
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