99 research outputs found
Identification of candidate regulatory sequences in mammalian 3' UTRs by statistical analysis of oligonucleotide distributions
3' untranslated regions (3' UTRs) contain binding sites for many regulatory
elements, and in particular for microRNAs (miRNAs). The importance of
miRNA-mediated post-transcriptional regulation has become increasingly clear in
the last few years.
We propose two complementary approaches to the statistical analysis of
oligonucleotide frequencies in mammalian 3' UTRs aimed at the identification of
candidate binding sites for regulatory elements. The first method is based on
the identification of sets of genes characterized by evolutionarily conserved
overrepresentation of an oligonucleotide. The second method is based on the
identification of oligonucleotides showing statistically significant strand
asymmetry in their distribution in 3' UTRs.
Both methods are able to identify many previously known binding sites located
in 3'UTRs, and in particular seed regions of known miRNAs. Many new candidates
are proposed for experimental verification.Comment: Added two reference
Computational identification of transcription factor binding sites by functional analysis of sets of genes sharing overrepresented upstream motifs
BACKGROUND: Transcriptional regulation is a key mechanism in the functioning
of the cell, and is mostly effected through transcription factors binding to
specific recognition motifs located upstream of the coding region of the
regulated gene. The computational identification of such motifs is made easier
by the fact that they often appear several times in the upstream region of the
regulated genes, so that the number of occurrences of relevant motifs is often
significantly larger than expected by pure chance. RESULTS: To exploit this
fact, we construct sets of genes characterized by the statistical
overrepresentation of a certain motif in their upstream regions. Then we study
the functional characterization of these sets by analyzing their annotation to
Gene Ontology terms. For the sets showing a statistically significant specific
functional characterization, we conjecture that the upstream motif
characterizing the set is a binding site for a transcription factor involved in
the regulation of the genes in the set. CONCLUSIONS: The method we propose is
able to identify many known binding sites in S. cerevisiae and new candidate
targets of regulation by known transcription factors. Its application to less
well studied organisms is likely to be valuable in the exploration of their
regulatory interaction network.Comment: 19 pages, 1 figure. Published version with several improvements.
Supplementary material available from the author
Ab initio identification of putative human transcription factor binding sites by comparative genomics
We discuss a simple and powerful approach for the ab initio identification of
cis-regulatory motifs involved in transcriptional regulation. The method we
present integrates several elements: human-mouse comparison, statistical
analysis of genomic sequences and the concept of coregulation. We apply it to a
complete scan of the human genome. By using the catalogue of conserved upstream
sequences collected in the CORG database we construct sets of genes sharing the
same overrepresented motif (short DNA sequence) in their upstream regions both
in human and in mouse. We perform this construction for all possible motifs
from 5 to 8 nucleotides in length and then filter the resulting sets looking
for two types of evidence of coregulation: first, we analyze the Gene Ontology
annotation of the genes in the set, searching for statistically significant
common annotations; second, we analyze the expression profiles of the genes in
the set as measured by microarray experiments, searching for evidence of
coexpression. The sets which pass one or both filters are conjectured to
contain a significant fraction of coregulated genes, and the upstream motifs
characterizing the sets are thus good candidates to be the binding sites of the
TF's involved in such regulation. In this way we find various known motifs and
also some new candidate binding sites.Comment: 22 pages, 2 figures. Supplementary material available from the
author
Correlated fragile site expression allows the identification of candidate fragile genes involved in immunity and associated with carcinogenesis
Common fragile sites (cfs) are specific regions in the human genome that are
particularly prone to genomic instability under conditions of replicative
stress. Several investigations support the view that common fragile sites play
a role in carcinogenesis. We discuss a genome-wide approach based on graph
theory and Gene Ontology vocabulary for the functional characterization of
common fragile sites and for the identification of genes that contribute to
tumour cell biology. CFS were assembled in a network based on a simple measure
of correlation among common fragile site patterns of expression. By applying
robust measurements to capture in quantitative terms the non triviality of the
network, we identified several topological features clearly indicating
departure from the Erdos-Renyi random graph model. The most important outcome
was the presence of an unexpected large connected component far below the
percolation threshold. Most of the best characterized common fragile sites
belonged to this connected component. By filtering this connected component
with Gene Ontology, statistically significant shared functional features were
detected. Common fragile sites were found to be enriched for genes associated
to the immune response and to mechanisms involved in tumour progression such as
extracellular space remodeling and angiogenesis. Our results support the
hypothesis that fragile sites serve a function; we propose that fragility is
linked to a coordinated regulation of fragile genes expression.Comment: 18 pages, accepted for publication in BMC Bioinformatic
MOCVD of AlN on epitaxial graphene at extreme temperatures
The initial stages of metal organic chemical vapor deposition (MOCVD) of AlN on epitaxial graphene at temperatures in excess of 1200 °C have been rationalized. The use of epitaxial graphene, in conjunction with high deposition temperatures, can deliver on the realization of nanometer thin AlN whose material quality is characterized by the appearance of luminescent centers with narrow spectral emission at room temperature. It has been elaborated, based on our previous comprehensive ab initio molecular dynamics simulations, that the impact of graphene on AlN growth consists in the way it promotes dissociation of the trimethylaluminum, (CH3)3Al, precursor with subsequent formation of Al adatoms during the initial stages of the deposition process. The high deposition temperatures ensure adequate surface diffusion of the Al adatoms which is an essential factor in material quality enhancement. The role of graphene in intervening with the dissociation of another precursor, trimethylgallium, (CH3)3Ga, has accordingly been speculated by presenting a case of propagation of ultrathin GaN of semiconductor quality. A lower deposition temperature of 1100 °C in this case has better preserved the structural integrity of epitaxial graphene. Breakage and decomposition of the graphene layers has been deduced in the case of AlN deposition at temperatures in excess of 1200 °C
Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector
A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements
Contributions of mean and shape of blood pressure distribution to worldwide trends and variations in raised blood pressure: A pooled analysis of 1018 population-based measurement studies with 88.6 million participants
© The Author(s) 2018. Background: Change in the prevalence of raised blood pressure could be due to both shifts in the entire distribution of blood pressure (representing the combined effects of public health interventions and secular trends) and changes in its high-blood-pressure tail (representing successful clinical interventions to control blood pressure in the hypertensive population). Our aim was to quantify the contributions of these two phenomena to the worldwide trends in the prevalence of raised blood pressure. Methods: We pooled 1018 population-based studies with blood pressure measurements on 88.6 million participants from 1985 to 2016. We first calculated mean systolic blood pressure (SBP), mean diastolic blood pressure (DBP) and prevalence of raised blood pressure by sex and 10-year age group from 20-29 years to 70-79 years in each study, taking into account complex survey design and survey sample weights, where relevant. We used a linear mixed effect model to quantify the association between (probittransformed) prevalence of raised blood pressure and age-group- and sex-specific mean blood pressure. We calculated the contributions of change in mean SBP and DBP, and of change in the prevalence-mean association, to the change in prevalence of raised blood pressure. Results: In 2005-16, at the same level of population mean SBP and DBP, men and women in South Asia and in Central Asia, the Middle East and North Africa would have the highest prevalence of raised blood pressure, and men and women in the highincome Asia Pacific and high-income Western regions would have the lowest. In most region-sex-age groups where the prevalence of raised blood pressure declined, one half or more of the decline was due to the decline in mean blood pressure. Where prevalence of raised blood pressure has increased, the change was entirely driven by increasing mean blood pressure, offset partly by the change in the prevalence-mean association. Conclusions: Change in mean blood pressure is the main driver of the worldwide change in the prevalence of raised blood pressure, but change in the high-blood-pressure tail of the distribution has also contributed to the change in prevalence, especially in older age groups
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