259 research outputs found
Visualizing dimensionality reduction of systems biology data
One of the challenges in analyzing high-dimensional expression data is the
detection of important biological signals. A common approach is to apply a
dimension reduction method, such as principal component analysis. Typically,
after application of such a method the data is projected and visualized in the
new coordinate system, using scatter plots or profile plots. These methods
provide good results if the data have certain properties which become visible
in the new coordinate system and which were hard to detect in the original
coordinate system. Often however, the application of only one method does not
suffice to capture all important signals. Therefore several methods addressing
different aspects of the data need to be applied. We have developed a framework
for linear and non-linear dimension reduction methods within our visual
analytics pipeline SpRay. This includes measures that assist the interpretation
of the factorization result. Different visualizations of these measures can be
combined with functional annotations that support the interpretation of the
results. We show an application to high-resolution time series microarray data
in the antibiotic-producing organism Streptomyces coelicolor as well as to
microarray data measuring expression of cells with normal karyotype and cells
with trisomies of human chromosomes 13 and 21
Adaptive Filtering Enhances Information Transmission in Visual Cortex
Sensory neuroscience seeks to understand how the brain encodes natural
environments. However, neural coding has largely been studied using simplified
stimuli. In order to assess whether the brain's coding strategy depend on the
stimulus ensemble, we apply a new information-theoretic method that allows
unbiased calculation of neural filters (receptive fields) from responses to
natural scenes or other complex signals with strong multipoint correlations. In
the cat primary visual cortex we compare responses to natural inputs with those
to noise inputs matched for luminance and contrast. We find that neural filters
adaptively change with the input ensemble so as to increase the information
carried by the neural response about the filtered stimulus. Adaptation affects
the spatial frequency composition of the filter, enhancing sensitivity to
under-represented frequencies in agreement with optimal encoding arguments.
Adaptation occurs over 40 s to many minutes, longer than most previously
reported forms of adaptation.Comment: 20 pages, 11 figures, includes supplementary informatio
Exponential Random Graph Modeling for Complex Brain Networks
Exponential random graph models (ERGMs), also known as p* models, have been
utilized extensively in the social science literature to study complex networks
and how their global structure depends on underlying structural components.
However, the literature on their use in biological networks (especially brain
networks) has remained sparse. Descriptive models based on a specific feature
of the graph (clustering coefficient, degree distribution, etc.) have dominated
connectivity research in neuroscience. Corresponding generative models have
been developed to reproduce one of these features. However, the complexity
inherent in whole-brain network data necessitates the development and use of
tools that allow the systematic exploration of several features simultaneously
and how they interact to form the global network architecture. ERGMs provide a
statistically principled approach to the assessment of how a set of interacting
local brain network features gives rise to the global structure. We illustrate
the utility of ERGMs for modeling, analyzing, and simulating complex
whole-brain networks with network data from normal subjects. We also provide a
foundation for the selection of important local features through the
implementation and assessment of three selection approaches: a traditional
p-value based backward selection approach, an information criterion approach
(AIC), and a graphical goodness of fit (GOF) approach. The graphical GOF
approach serves as the best method given the scientific interest in being able
to capture and reproduce the structure of fitted brain networks
Sequence Conservation in Plasmodium falciparum α-Helical Coiled Coil Domains Proposed for Vaccine Development
BACKGROUND: The availability of the P. falciparum genome has led to novel ways to identify potential vaccine candidates. A new approach for antigen discovery based on the bioinformatic selection of heptad repeat motifs corresponding to alpha-helical coiled coil structures yielded promising results. To elucidate the question about the relationship between the coiled coil motifs and their sequence conservation, we have assessed the extent of polymorphism in putative alpha-helical coiled coil domains in culture strains, in natural populations and in the single nucleotide polymorphism data available at PlasmoDB. METHODOLOGY/PRINCIPAL FINDINGS: 14 alpha-helical coiled coil domains were selected based on preclinical experimental evaluation. They were tested by PCR amplification and sequencing of different P. falciparum culture strains and field isolates. We found that only 3 out of 14 alpha-helical coiled coils showed point mutations and/or length polymorphisms. Based on promising immunological results 5 of these peptides were selected for further analysis. Direct sequencing of field samples from Papua New Guinea and Tanzania showed that 3 out of these 5 peptides were completely conserved. An in silico analysis of polymorphism was performed for all 166 putative alpha-helical coiled coil domains originally identified in the P. falciparum genome. We found that 82% (137/166) of these peptides were conserved, and for one peptide only the detected SNPs decreased substantially the probability score for alpha-helical coiled coil formation. More SNPs were found in arrays of almost perfect tandem repeats. In summary, the coiled coil structure prediction was rarely modified by SNPs. The analysis revealed a number of peptides with strictly conserved alpha-helical coiled coil motifs. CONCLUSION/SIGNIFICANCE: We conclude that the selection of alpha-helical coiled coil structural motifs is a valuable approach to identify potential vaccine targets showing a high degree of conservation
Bayesian paternity analysis and mating patterns in a parasitic nematode, Trichostrongylus tenuis
Mating behaviour is a fundamental aspect of the evolutionary ecology of sexually reproducing species, but one that has been under-researched in parasitic nematodes. We analysed mating behaviour in the parasitic nematode Trichostrongylus tenuis by performing a paternity analysis in a population from a single red grouse host. Paternity of the 150 larval offspring of 25 mothers (sampled from one of the two host caeca) was assigned among 294 candidate fathers (sampled from both caeca). Each candidate father's probability of paternity of each offspring was estimated from 10-locus microsatellite genotypes. Seventy-six (51%) offspring were assigned a father with a probability of >0.8, and the estimated number of unsampled males was 136 (95% credible interval (CI) 77-219). The probability of a male from one caecum fathering an offspring in the other caecum was estimated as 0.024 (95% CI 0.003-0.077), indicating that the junction of the caeca is a strong barrier to dispersal. Levels of promiscuity (defined as the probability of two of an adult's offspring sharing only one parent) were high for both sexes. Variance in male reproductive success was moderately high, possibly because of a combination of random mating and high variance in post-copulatory reproductive success. These results provide the first data on individual mating behaviour among parasitic nematodes
Angiomyolipoma Have Common Mutations in TSC2 but No Other Common Genetic Events
Renal angiomyolipoma are part of the PEComa family of neoplasms, and occur both in association with Tuberous Sclerosis Complex (TSC) and independent of that disorder. Previous studies on the molecular genetic alterations that occur in angiomyolipoma are very limited. We evaluated 9 angiomyolipoma for which frozen tissue was available from a consecutive surgical series. Seven of 8 samples subjected to RT-PCR-cDNA sequencing showed mutations in TSC2; none showed mutations in TSC1 or RHEB. Six of the seven mutations were deletions. We searched for 983 activating and inactivating mutations in 115 genes, and found none in these tumors. Similarly analysis for genomic regions of loss or gain, assessed by Affymetrix SNP6.0 analysis, showed no abnormalities. Loss of heterozygosity in the TSC2 region was commonly seen, except in patients with low frequency TSC2 mutations. We conclude that sporadic renal angiomyolipoma usually have mutations in TSC2, but not TSC1 or RHEB, and have no other common genomic events, among those we searched for. However, chromosomal translocations and gene fusion events were not assessed here. TSC2 inactivation by mutation is a consistent and likely necessary genetic event in the pathogenesis of most angiomyolipoma
Hypoxia-Induced Mitogenic Factor (HIMF/FIZZ1/RELMα) Recruits Bone Marrow-Derived Cells to the Murine Pulmonary Vasculature
. and localized to the media layer of the vessels. This finding suggests that these cells are of mesenchymal origin and differentiate toward myofibroblast and vascular smooth muscle. Structural location in the media of small vessels suggests a functional role in the lung vasculature. To examine a potential mechanism for HIMF-dependent recruitment of mesenchymal stem cells to the pulmonary vasculature, we performed a cell migration assay using cultured human mesenchymal stem cells (HMSCs). The addition of recombinant HIMF induced migration of HMSCs in a phosphoinosotide-3-kinase-dependent manner.These results demonstrate HIMF-dependent recruitment of BMD mesenchymal-like cells to the remodeling pulmonary vasculature
A physiological time analysis of the duration of the gonotrophic cycle of Anopheles pseudopunctipennis and its implications for malaria transmission in Bolivia
<p>Abstract</p> <p>Background</p> <p>The length of the gonotrophic cycle varies the vectorial capacity of a mosquito vector and therefore its exact estimation is important in epidemiological modelling. Because the gonotrophic cycle length depends on temperature, its estimation can be satisfactorily computed by means of physiological time analysis.</p> <p>Methods</p> <p>A model of physiological time was developed and calibrated for <it>Anopheles pseudopunctipennis</it>, one of the main malaria vectors in South America, using data from laboratory temperature controlled experiments. The model was validated under varying temperatures and could predict the time elapsed from blood engorgement to oviposition according to the temperature.</p> <p>Results</p> <p>In laboratory experiments, a batch of <it>An. pseudopunctipennis </it>fed at the same time may lay eggs during several consecutive nights (2–3 at high temperature and > 10 at low temperature). The model took into account such pattern and was used to predict the range of the gonotrophic cycle duration of <it>An. pseudopunctipennis </it>in four characteristic sites of Bolivia. It showed that the predicted cycle duration for <it>An. pseudopunctipennis </it>exhibited a seasonal pattern, with higher variances where climatic conditions were less stable. Predicted mean values of the (minimum) duration ranged from 3.3 days up to > 10 days, depending on the season and the geographical location. The analysis of ovaries development stages of field collected biting mosquitoes indicated that the phase 1 of Beklemishev might be of significant duration for <it>An. pseudopunctipennis</it>. The gonotrophic cycle length of <it>An. pseudopunctipennis </it>correlates with malaria transmission patterns observed in Bolivia which depend on locations and seasons.</p> <p>Conclusion</p> <p>A new presentation of cycle length results taking into account the number of ovipositing nights and the proportion of mosquitoes laying eggs is suggested. The present approach using physiological time analysis might serve as an outline to other similar studies and allows the inclusion of temperature effects on the gonotrophic cycle in transmission models. However, to better explore the effects of temperature on malaria transmission, the others parameters of the vectorial capacity should be included in the analysis and modelled accordingly.</p
Defining the Sister Rat Mammary Tumor Cell Lines HH-16 cl.2/1 and HH-16.cl.4 as an In Vitro Cell Model for Erbb2
Cancer cell lines have been shown to be reliable tools in genetic studies of breast cancer, and the characterization of these lines indicates that they are good models for studying the biological mechanisms underlying this disease. Here, we describe the molecular cytogenetic/genetic characterization of two sister rat mammary tumor cell lines, HH-16 cl.2/1 and HH-16.cl.4, for the first time. Molecular cytogenetic analysis using rat and mouse chromosome paint probes and BAC/PAC clones allowed the characterization of clonal chromosome rearrangements; moreover, this strategy assisted in revealing detected breakpoint regions and complex chromosome rearrangements. This comprehensive cytogenetic analysis revealed an increase in the number of copies of the Mycn and Erbb2 genes in the investigated cell lines. To analyze its possible correlation with expression changes, relative RNA expression was assessed by real-time reverse transcription quantitative PCR and RNA FISH. Erbb2 was found to be overexpressed in HH-16.cl.4, but not in the sister cell line HH-16 cl.2/1, even though these lines share the same initial genetic environment. Moreover, the relative expression of Erbb2 decreased after global genome demethylation in the HH-16.cl.4 cell line. As these cell lines are commercially available and have been used in previous studies, the present detailed characterization improves their value as an in vitro cell model. We believe that the development of appropriate in vitro cell models for breast cancer is of crucial importance for revealing the genetic and cellular pathways underlying this neoplasy and for employing them as experimental tools to assist in the generation of new biotherapies
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