Sub-kHz linewidth VECSEL for cold atoms experiments

We report sub-kHz linewidth operation of a frequency-stabilized, AlGaInP-based vertical-external-cavity surface-emitting laser (VECSEL) at 689nm, suitable for Strontium cold atom experiments. 170mW was emitted with linewidth ≤200Hz, determined via an optical beat note measurement

Semiconductor disk lasers: the future's bright; the colour's flexible

Presentation describing semiconductor disk lasers, their use and how they work

Classification using distance nearest neighbours

This paper proposes a new probabilistic classification algorithm using a Markov random field approach. The joint distribution of class labels is explicitly modelled using the distances between feature vectors. Intuitively, a class label should depend more on class labels which are closer in the feature space, than those which are further away. Our approach builds on previous work by Holmes and Adams (2002, 2003) and Cucala et al. (2008). Our work shares many of the advantages of these approaches in providing a probabilistic basis for the statistical inference. In comparison to previous work, we present a more efficient computational algorithm to overcome the intractability of the Markov random field model. The results of our algorithm are encouraging in comparison to the k-nearest neighbour algorithm.Comment: 12 pages, 2 figures. To appear in Statistics and Computin

The Iterative Signature Algorithm for the analysis of large scale gene expression data

We present a new approach for the analysis of genome-wide expression data. Our method is designed to overcome the limitations of traditional techniques, when applied to large-scale data. Rather than alloting each gene to a single cluster, we assign both genes and conditions to context-dependent and potentially overlapping transcription modules. We provide a rigorous definition of a transcription module as the object to be retrieved from the expression data. An efficient algorithm, that searches for the modules encoded in the data by iteratively refining sets of genes and conditions until they match this definition, is established. Each iteration involves a linear map, induced by the normalized expression matrix, followed by the application of a threshold function. We argue that our method is in fact a generalization of Singular Value Decomposition, which corresponds to the special case where no threshold is applied. We show analytically that for noisy expression data our approach leads to better classification due to the implementation of the threshold. This result is confirmed by numerical analyses based on in-silico expression data. We discuss briefly results obtained by applying our algorithm to expression data from the yeast S. cerevisiae.Comment: Latex, 36 pages, 8 figure

Local linear regression with adaptive orthogonal fitting for the wind power application

Short-term forecasting of wind generation requires a model of the function for the conversion of me-teorological variables (mainly wind speed) to power production. Such a power curve is nonlinear and bounded, in addition to being nonstationary. Local linear regression is an appealing nonparametric ap-proach for power curve estimation, for which the model coefficients can be tracked with recursive Least Squares (LS) methods. This may lead to an inaccurate estimate of the true power curve, owing to the assumption that a noise component is present on the response variable axis only. Therefore, this assump-tion is relaxed here, by describing a local linear regression with orthogonal fit. Local linear coefficients are defined as those which minimize a weighted Total Least Squares (TLS) criterion. An adaptive es-timation method is introduced in order to accommodate nonstationarity. This has the additional benefit of lowering the computational costs of updating local coefficients every time new observations become available. The estimation method is based on tracking the left-most eigenvector of the augmented covari-ance matrix. A robustification of the estimation method is also proposed. Simulations on semi-artificial datasets (for which the true power curve is available) underline the properties of the proposed regression and related estimation methods. An important result is the significantly higher ability of local polynomia

Automated workflow-based exploitation of pathway databases provides new insights into genetic associations of metabolite profiles

Background: Genome-wide association studies (GWAS) have identified many common single nucleotide polymorphisms (SNPs) that associate with clinical phenotypes, but these SNPs usually explain just a small part of the heritability and have relatively modest effect sizes. In contrast, SNPs that associate with metabolite levels generally explain a higher percentage of the genetic variation and demonstrate larger effect sizes. Still, the discovery of SNPs associated with metabolite levels is challenging since testing all metabolites measured in typical metabolomics studies with all SNPs comes with a severe multiple testing penalty. We have developed an automated workflow approach that utilizes prior knowledge of biochemical pathways present in databases like KEGG and BioCyc to generate a smaller SNP set relevant to the metabolite. This paper explores the opportunities and challenges in the analysis of GWAS of metabolomic phenotypes and provides novel insights into the genetic basis of metabolic variation through the re-analysis of published GWAS datasets. Results: Re-analysis of the published GWAS dataset from Illig et al. (Nature Genetics, 2010) using a pathway-based workflow (http://www.myexperiment.org/packs/319.html), confirmed previously identified hits and identified a new locus of human metabolic individuality, associating Aldehyde dehydrogenase family1 L1 (ALDH1L1) with serine/glycine ratios in blood. Replication in an independent GWAS dataset of phospholipids (Demirkan et al., PLoS Genetics, 2012) identified two novel loci supported by additional literature evidence: GPAM (Glycerol-3 phosphate acyltransferase) and CBS (Cystathionine beta-synthase). In addition, the workflow approach provided novel insight into the affected pathways and relevance of some of these gene-metabolite pairs in disease development and progression. Conclusions: We demonstrate the utility of automated exploitation of background knowledge present in pathway databases for the analysis of GWAS datasets of metabolomic phenotypes. We report novel loci and potential biochemical mechanisms that contribute to our understanding of the genetic basis of metabolic variation and its relationship to disease development and progression

Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants

Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Peer reviewe