1,810 research outputs found
A Multi-Layer Method to Study Genome-Scale Positions of Nucleosomes
The basic unit of eukaryotic chromatin is the nucleosome, consisting of about 150 by of DNA wrapped around a protein core made of histone proteins. Nucleosomes position is modulated in vivo to regulate fundamental nuclear processes. To measure nucleosome positions on a genomic scale both theoretical and experimental approaches have been recently reported. We have developed a new method, Multi-Layer Model (MLM), for the analysis of nucleosome position data obtained with microarray-based approach. The MLM is a feature extraction method in which the input data is processed by a classifier to distinguish between several kinds of patterns. We applied our method to simulated-synthetic and experimental nucleosome position data and found that besides a high nucleosome recognition and a strong agreement with standard statistical methods, the MLM can identify distinct classes of nucleosomes, making it an important tool for the genome wide analysis of nucleosome position and function. In conclusion, the MLM allows a better representation of nucleosome position data and a significant reduction in computational time
Quantitative test of the barrier nucleosome model for statistical positioning of nucleosomes up- and downstream of transcription start sites
The positions of nucleosomes in eukaryotic genomes determine which parts of
the DNA sequence are readily accessible for regulatory proteins and which are
not. Genome-wide maps of nucleosome positions have revealed a salient pattern
around transcription start sites, involving a nucleosome-free region (NFR)
flanked by a pronounced periodic pattern in the average nucleosome density.
While the periodic pattern clearly reflects well-positioned nucleosomes, the
positioning mechanism is less clear. A recent experimental study by Mavrich et
al. argued that the pattern observed in S. cerevisiae is qualitatively
consistent with a `barrier nucleosome model', in which the oscillatory pattern
is created by the statistical positioning mechanism of Kornberg and Stryer. On
the other hand, there is clear evidence for intrinsic sequence preferences of
nucleosomes, and it is unclear to what extent these sequence preferences affect
the observed pattern. To test the barrier nucleosome model, we quantitatively
analyze yeast nucleosome positioning data both up- and downstream from NFRs.
Our analysis is based on the Tonks model of statistical physics which
quantifies the interplay between the excluded-volume interaction of nucleosomes
and their positional entropy. We find that although the typical patterns on the
two sides of the NFR are different, they are both quantitatively described by
the same physical model, with the same parameters, but different boundary
conditions. The inferred boundary conditions suggest that the first nucleosome
downstream from the NFR (the +1 nucleosome) is typically directly positioned
while the first nucleosome upstream is statistically positioned via a
nucleosome-repelling DNA region. These boundary conditions, which can be
locally encoded into the genome sequence, significantly shape the statistical
distribution of nucleosomes over a range of up to ~1000 bp to each side.Comment: includes supporting materia
Importance Sampling for Objetive Funtion Estimations in Neural Detector Traing Driven by Genetic Algorithms
To train Neural Networks (NNs) in a supervised way, estimations of an objective function must be carried out. The value of this function decreases as the training progresses and so, the number of test observations necessary for an accurate estimation has to be increased. Consequently, the training computational cost is unaffordable for very low objective function value estimations, and the use of Importance Sampling (IS) techniques becomes convenient. The study of three different objective functions is considered, which implies the proposal of estimators of the objective function using IS techniques: the Mean-Square error, the Cross Entropy error and the Misclassification error criteria. The values of these functions are estimated by IS techniques, and the results are used to train NNs by the application of Genetic Algorithms. Results for a binary detection in Gaussian noise are provided. These results show the evolution of the parameters during the training and the performances of the proposed detectors in terms of error probability and Receiver Operating Characteristics curves. At the end of the study, the obtained results justify the convenience of using IS in the training
Mapping Dynamic Histone Acetylation Patterns to Gene Expression in Nanog-depleted Murine Embryonic Stem Cells
Embryonic stem cells (ESC) have the potential to self-renew indefinitely and
to differentiate into any of the three germ layers. The molecular mechanisms
for self-renewal, maintenance of pluripotency and lineage specification are
poorly understood, but recent results point to a key role for epigenetic
mechanisms. In this study, we focus on quantifying the impact of histone 3
acetylation (H3K9,14ac) on gene expression in murine embryonic stem cells. We
analyze genome-wide histone acetylation patterns and gene expression profiles
measured over the first five days of cell differentiation triggered by
silencing Nanog, a key transcription factor in ESC regulation. We explore the
temporal and spatial dynamics of histone acetylation data and its correlation
with gene expression using supervised and unsupervised statistical models. On a
genome-wide scale, changes in acetylation are significantly correlated to
changes in mRNA expression and, surprisingly, this coherence increases over
time. We quantify the predictive power of histone acetylation for gene
expression changes in a balanced cross-validation procedure. In an in-depth
study we focus on genes central to the regulatory network of Mouse ESC,
including those identified in a recent genome-wide RNAi screen and in the
PluriNet, a computationally derived stem cell signature. We find that compared
to the rest of the genome, ESC-specific genes show significantly more
acetylation signal and a much stronger decrease in acetylation over time, which
is often not reflected in an concordant expression change. These results shed
light on the complexity of the relationship between histone acetylation and
gene expression and are a step forward to dissect the multilayer regulatory
mechanisms that determine stem cell fate.Comment: accepted at PLoS Computational Biolog
Body mass index and smoking-related lung cancer risk in the Singapore Chinese Health Study
10.1038/sj.bjc.6605496British Journal of Cancer1023610-61
Wide-Scale Analysis of Human Functional Transcription Factor Binding Reveals a Strong Bias towards the Transcription Start Site
We introduce a novel method to screen the promoters of a set of genes with
shared biological function, against a precompiled library of motifs, and find
those motifs which are statistically over-represented in the gene set. The gene
sets were obtained from the functional Gene Ontology (GO) classification; for
each set and motif we optimized the sequence similarity score threshold,
independently for every location window (measured with respect to the TSS),
taking into account the location dependent nucleotide heterogeneity along the
promoters of the target genes. We performed a high throughput analysis,
searching the promoters (from 200bp downstream to 1000bp upstream the TSS), of
more than 8000 human and 23,000 mouse genes, for 134 functional Gene Ontology
classes and for 412 known DNA motifs. When combined with binding site and
location conservation between human and mouse, the method identifies with high
probability functional binding sites that regulate groups of biologically
related genes. We found many location-sensitive functional binding events and
showed that they clustered close to the TSS. Our method and findings were put
to several experimental tests. By allowing a "flexible" threshold and combining
our functional class and location specific search method with conservation
between human and mouse, we are able to identify reliably functional TF binding
sites. This is an essential step towards constructing regulatory networks and
elucidating the design principles that govern transcriptional regulation of
expression. The promoter region proximal to the TSS appears to be of central
importance for regulation of transcription in human and mouse, just as it is in
bacteria and yeast.Comment: 31 pages, including Supplementary Information and figure
Ultrathin compound semiconductor on insulator layers for high performance nanoscale transistors
Over the past several years, the inherent scaling limitations of electron
devices have fueled the exploration of high carrier mobility semiconductors as
a Si replacement to further enhance the device performance. In particular,
compound semiconductors heterogeneously integrated on Si substrates have been
actively studied, combining the high mobility of III-V semiconductors and the
well-established, low cost processing of Si technology. This integration,
however, presents significant challenges. Conventionally, heteroepitaxial
growth of complex multilayers on Si has been explored. Besides complexity, high
defect densities and junction leakage currents present limitations in the
approach. Motivated by this challenge, here we utilize an epitaxial transfer
method for the integration of ultrathin layers of single-crystalline InAs on
Si/SiO2 substrates. As a parallel to silicon-on-insulator (SOI) technology14,we
use the abbreviation "XOI" to represent our compound semiconductor-on-insulator
platform. Through experiments and simulation, the electrical properties of InAs
XOI transistors are explored, elucidating the critical role of quantum
confinement in the transport properties of ultrathin XOI layers. Importantly, a
high quality InAs/dielectric interface is obtained by the use of a novel
thermally grown interfacial InAsOx layer (~1 nm thick). The fabricated FETs
exhibit an impressive peak transconductance of ~1.6 mS/{\mu}m at VDS=0.5V with
ON/OFF current ratio of greater than 10,000 and a subthreshold swing of 107-150
mV/decade for a channel length of ~0.5 {\mu}m
Genome wide association mapping of grain arsenic, copper, molybdenum and zinc in rice (Oryza sativa L.) grown at four international field sites
Peer reviewedPublisher PD
The Galactic Center Black Hole Laboratory
The super-massive 4 million solar mass black hole Sagittarius~A* (SgrA*)
shows flare emission from the millimeter to the X-ray domain. A detailed
analysis of the infrared light curves allows us to address the accretion
phenomenon in a statistical way. The analysis shows that the near-infrared
flare amplitudes are dominated by a single state power law, with the low states
in SgrA* limited by confusion through the unresolved stellar background. There
are several dusty objects in the immediate vicinity of SgrA*. The source G2/DSO
is one of them. Its nature is unclear. It may be comparable to similar stellar
dusty sources in the region or may consist predominantly of gas and dust. In
this case a particularly enhanced accretion activity onto SgrA* may be expected
in the near future. Here the interpretation of recent data and ongoing
observations are discussed.Comment: 30 pages - 7 figures - accepted for publication by Springer's
"Fundamental Theories of Physics" series; summarizing GC contributions of 2
conferences: 'Equations of Motion in Relativistic Gravity' at the
Physikzentrum Bad Honnef, Bad Honnef, Germany, (Feb. 17-23, 2013) and the
COST MP0905 'The Galactic Center Black Hole Laboratory' Granada, Spain (Nov.
19 - 22, 2013
- …