Accelerating MCMC via Parallel Predictive Prefetching

We present a general framework for accelerating a large class of widely used Markov chain Monte Carlo (MCMC) algorithms. Our approach exploits fast, iterative approximations to the target density to speculatively evaluate many potential future steps of the chain in parallel. The approach can accelerate computation of the target distribution of a Bayesian inference problem, without compromising exactness, by exploiting subsets of data. It takes advantage of whatever parallel resources are available, but produces results exactly equivalent to standard serial execution. In the initial burn-in phase of chain evaluation, it achieves speedup over serial evaluation that is close to linear in the number of available cores

Characterization of the cysteine protease, PhCP10, during the senescence of Petunia x hybrida flowers

Proteases play an important role in the degradation and remobilization of proteins during flower senescence. The majority of proteases that are upregulated during senescence and programmed cell death are from the cysteine protease class of proteases. Recently, nine putative cysteine proteases were identified from Petunia x hybrida. Six of the nine cysteine proteases were upregulated during petal senescence. One cysteine protease, PhCP10, is upregulated early in senescence, is expressed only in senescing tissues and appears to be regulated by ethylene. The PhCP10 sequence shows high homology to SAG12 (senescence-associated gene) from Arabidopsis. SAG12 is senescence specific in Arabidopsis leaves, but little is known about its expression in flowers. TAIL-PCR was preformed to obtain the PhCP10 promoter . The PhCP10 promoter sequence also shares homology with the senescence-specific and basal promoter regions of SAG12. Promoter constructs driving GFP expression have been analyzed utilizing transient expression in lima bean cotyledons and in petunia flowers. Transient expression in lima beans and petunia flowers has detected a possible regulatory element that appears to enhance PhCP10 expression in a similar manner to the enhancer region in the SAG12 promoter. We are currently transforming petunias with the PhCP10:GFP constructs to further characterize the temporal and spatial expression of PhCP10 during flower senescence and following ethylene treatment

Parallelization by Simulated Tunneling

As highly parallel heterogeneous computers become commonplace, automatic parallelization of software is an increasingly critical unsolved problem. Continued progress on this problem will require large quantities of information about the runtime structure of sequential programs to be stored and reasoned about. Manually formalizing all this information through traditional approaches, which rely on semantic analysis at the language or instruction level, has historically proved challenging. We take a lower level approach, eschewing semantic analysis and instead modeling von Neumann computation as a dynamical system, i.e., a state space and an evolution rule, which gives a natural way to use probabilistic inference to automatically learn powerful representations of this information. This model enables a promising new approach to automatic parallelization, in which probability distributions empirically learned over the state space are used to guide speculative solvers. We describe a prototype virtual machine that uses this model of computation to automatically achieve linear speedups for an important class of deterministic, sequential Intel binary programs through statistical machine learning and a speculative, generalized form of memoization.Engineering and Applied Science

Numerical study of scars in a chaotic billiard

We study numerically the scaling properties of scars in stadium billiard. Using the semiclassical criterion, we have searched systematically the scars of the same type through a very wide range, from ground state to as high as the 1 millionth state. We have analyzed the integrated probability density along the periodic orbit. The numerical results confirm that the average intensity of certain types of scars is independent of $\hbar$ rather than scales with $\sqrt{\hbar}$. Our findings confirm the theoretical predictions of Robnik (1989).Comment: 7 pages in Revtex 3.1, 5 PS figures available upon request. To appear in Phys. Rev. E, Vol. 55, No. 5, 199

Paternal obesity is associated with IGF2 hypomethylation in newborns: results from a Newborn Epigenetics Study (NEST) cohort

Data from epidemiological and animal model studies suggest that nutrition during pregnancy may affect the health status of subsequent generations. These transgenerational effects are now being explained by disruptions at the level of the epigenetic machinery. Besides in vitro environmental exposures, the possible impact on the reprogramming of methylation profiles at imprinted genes at a much earlier time point, such as during spermatogenesis or oogenesis, has not previously been considered. In this study, our aim was to determine associations between preconceptional obesity and DNA methylation profiles in the offspring, particularly at the differentially methylated regions (DMRs) of the imprinted Insulin-like Growth Factor 2 (IGF2) gene

In utero tobacco smoke exposure, DNA methylation, and asthma in Latino children.

BackgroundMaternal smoking during pregnancy is a risk factor for chronic disease later in life and has been associated with variability of DNA methylation at specific cytosine-phosphate-guanine (CpG) loci. We assessed the role of DNA methylation as a potential mediator of adverse effects of in utero tobacco smoke exposures on asthma outcomes in Latino children from the US mainland and Puerto Rico.MethodsRelationships between self-reported exposure and DNA methylation at CpG loci previously reported to be associated with maternal smoking were assessed in a subsample consisting of 572 children aged 8-21 years (310 cases with asthma, 262 healthy controls), sampled from a larger asthma case-control study. Subsequently, we assessed associations between top loci and asthma-related outcomes, followed by mediation analysis for loci for which associations with outcomes were observed.ResultsSelf-reported maternal smoking was associated with a -1.5% (95% confidence interval (CI) = -2.4%, -0.6%) lower methylation at CpG locus cg05575921 on the AHRR gene; a 1% increase in DNA methylation at the same locus resulted in an odds ratio (OR) of 0.90 (95% CI = 0.83, 0.96) for the odds of asthma. The OR for the indirect effect of maternal smoking on asthma mediated through methylation at the cg05575921 locus was 1.18 (95% CI = 1.07, 1.68), compared to the OR for the total effect of exposure in the parent study of 1.48 (95% CI = 1.03, 2.11).ConclusionsOur findings suggest potential mediation by DNA methylation in the association between maternal smoking during pregnancy and asthma status

Comparison of sequencing-based methods to profile DNA methylation and identification of monoallelic epigenetic modifications.

Analysis of DNA methylation patterns relies increasingly on sequencing-based profiling methods. The four most frequently used sequencing-based technologies are the bisulfite-based methods MethylC-seq and reduced representation bisulfite sequencing (RRBS), and the enrichment-based techniques methylated DNA immunoprecipitation sequencing (MeDIP-seq) and methylated DNA binding domain sequencing (MBD-seq). We applied all four methods to biological replicates of human embryonic stem cells to assess their genome-wide CpG coverage, resolution, cost, concordance and the influence of CpG density and genomic context. The methylation levels assessed by the two bisulfite methods were concordant (their difference did not exceed a given threshold) for 82% for CpGs and 99% of the non-CpG cytosines. Using binary methylation calls, the two enrichment methods were 99% concordant and regions assessed by all four methods were 97% concordant. We combined MeDIP-seq with methylation-sensitive restriction enzyme (MRE-seq) sequencing for comprehensive methylome coverage at lower cost. This, along with RNA-seq and ChIP-seq of the ES cells enabled us to detect regions with allele-specific epigenetic states, identifying most known imprinted regions and new loci with monoallelic epigenetic marks and monoallelic expression

Heritable rather than age-related environmental and stochastic factors dominate variation in DNA methylation of the human IGF2/H19 locus.

Epigenetic variation may significantly contribute to the risk of common disease. Currently, little is known about the extent and causes of epigenetic variation. Here, we investigated the contribution of heritable influences and the combined effect of environmental and stochastic factors to variation in DNA methylation of the IGF2/H19 locus. Moreover, we tested whether this locus was subject to age-related degeneration of epigenetic patterns as was previously suggested for global methylation. We measured methylation of the H19 and IGF2 differentially methylated regions (DMRs) in 196 adolescent and 176 middle-aged twins using a recently developed mass spectrometry-based method. We observed substantial variation in DNA methylation across individuals, underscoring that DNA methylation is a quantitative trait. Analysis of data in monozygotic and dizygotic twins revealed that a significant part of this variation could be attributed to heritable factors. The heritability of methylation of individual CpG sites varied between 20 and 74% for the H19 DMR and was even higher, between 57 and 97%, for the IGF2 DMR. Remarkably, the combined influence of environmental and stochastic factors on DNA methylation was not greater in middle-age than in adolescence, suggesting a limited role for age-related degeneration of methylation patterns at this locus. Single nucleotide polymorphisms in the IGF2/H19 locus were significantly associated with DNA methylation of the IGF2 DMR (P = 0.004). A preliminary analysis suggested an association between H19 DMR methylation and body size (P < 0.05). Our study shows that variation in DNA methylation of the IGF2/H19 locus is mainly determined by heritable factors and single nucleotide polymorphisms (SNPs) in cis, rather than the cumulative effect of environmental and stochastic factors occurring with age. © 2007 Oxford University Press