15,168 research outputs found
An Empirical Bayes Approach for Multiple Tissue eQTL Analysis
Expression quantitative trait loci (eQTL) analyses, which identify genetic
markers associated with the expression of a gene, are an important tool in the
understanding of diseases in human and other populations. While most eQTL
studies to date consider the connection between genetic variation and
expression in a single tissue, complex, multi-tissue data sets are now being
generated by the GTEx initiative. These data sets have the potential to improve
the findings of single tissue analyses by borrowing strength across tissues,
and the potential to elucidate the genotypic basis of differences between
tissues.
In this paper we introduce and study a multivariate hierarchical Bayesian
model (MT-eQTL) for multi-tissue eQTL analysis. MT-eQTL directly models the
vector of correlations between expression and genotype across tissues. It
explicitly captures patterns of variation in the presence or absence of eQTLs,
as well as the heterogeneity of effect sizes across tissues. Moreover, the
model is applicable to complex designs in which the set of donors can (i) vary
from tissue to tissue, and (ii) exhibit incomplete overlap between tissues. The
MT-eQTL model is marginally consistent, in the sense that the model for a
subset of tissues can be obtained from the full model via marginalization.
Fitting of the MT-eQTL model is carried out via empirical Bayes, using an
approximate EM algorithm. Inferences concerning eQTL detection and the
configuration of eQTLs across tissues are derived from adaptive thresholding of
local false discovery rates, and maximum a-posteriori estimation, respectively.
We investigate the MT-eQTL model through a simulation study, and rigorously
establish the FDR control of the local FDR testing procedure under mild
assumptions appropriate for dependent data.Comment: accepted by Biostatistic
On the Distribution of the Fourier Spectrum of Halfspaces
Bourgain showed that any noise stable Boolean function can be
well-approximated by a junta. In this note we give an exponential sharpening of
the parameters of Bourgain's result under the additional assumption that is
a halfspace
Electrically driven spin resonance in a bent disordered carbon nanotube
Resonant manipulation of carbon nanotube valley-spin qubits by an electric
field is investigated theoretically. We develop a new analysis of electrically
driven spin resonance exploiting fixed physical characteristics of the
nanotube: a bend and inhomogeneous disorder. The spectrum is simulated for an
electron valley-spin qubit coupled to a hole valley-spin qubit and an impurity
electron spin, and features that coincide with a recent measurement are
identified. We show that the same mechanism allows resonant control of the full
four-dimensional spin-valley space.Comment: 11 pages, 7 figure
Compound C inhibits nonsense-mediated RNA decay independently of AMPK
The nonsense mediated RNA decay (NMD) pathway safeguards the integrity of the transcriptome by targeting mRNAs with premature translation termination codons (PTCs) for degradation. It also regulates gene expression by degrading a large number of non-mutant RNAs (including mRNAs and noncoding RNAs) that bear NMD-inducing features. Consequently, NMD has been shown to influence development, cellular response to stress, and clinical outcome of many genetic diseases. Small molecules that can modulate NMD activity provide critical tools for understanding the mechanism and physiological functions of NMD, and they also offer potential means for treating certain genetic diseases and cancer. Therefore, there is an intense interest in identifying small-molecule NMD inhibitors or enhancers. It was previously reported that both inhibition of NMD and treatment with the AMPK-selective inhibitor Compound C (CC) induce autophagy in human cells, raising the possibility that CC may be capable of inhibiting NMD. Here we show that CC indeed has a NMD-inhibitory activity. Inhibition of NMD by CC is, however, independent of AMPK activity. As a competitive ATP analog, CC does not affect the kinase activity of SMG1, an essential NMD factor and the only known kinase in the NMD pathway. However, CC treatment down-regulates the protein levels of several NMD factors. The induction of autophagy by CC treatment is independent of ATF4, a NMD target that has been shown to promote autophagy in response to NMD inhibition. Our results reveal a new activity of CC as a NMD inhibitor, which has implications for its use in basic research and drug development
Directed flow of neutral strange particles at AGS
Directed flow of neutral strange particles in heavy ion collisions at AGS is
studied in the ART transport model. Using a lambda mean-field potential which
is 2/3 of that for a nucleon as predicted by the constituent quark model,
lambdas are found to flow with protons but with a smaller flow parameter as
observed in experiments. For kaons, their repulsive potential, which is
calculated from the impulse approximation using the measured kaon-nucleon
scattering length, leads to a smaller anti-flow than that shown in the
preliminary E895 data. Implications of this discrepancy are discussed.Comment: 6 pages, 2 figure
A Novel Family of Mobile Genetic Elements Is Limited to the Germline Genome in \u3cem\u3eTetrahymena Thermophila\u3c/em\u3e
In the ciliated protozoan Tetrahymena thermophila, extensive DNA elimination is associated with differentiation of the somatic macronucleus from the germline micronucleus. This study describes the isolation and complete characterization of Tlr elements, a family of approximately 30 micronuclear DNA sequences that are efficiently eliminated from the developing macronucleus. The data indicate that Tlr elements are comprised of an ~22 kb internal region flanked by complex and variable termini. The Tlr internal region is highly conserved among family members and contains 15 open reading frames, some of which resemble genes encoded by transposons and viruses. The Tlr termini appear to be long inverted repeats consisting of (i) a variable region containing multiple direct repeats which differ in number and sequence from element to element and (ii) a conserved terminal 47 bp sequence. Taken together, these results suggest that Tlr elements comprise a novel family of mobile genetic elements that are confined to the Tetrahymena germline genome. Possible mechanisms of developmentally programmed Tlr elimination are discussed
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