Safe and complete contig assembly via omnitigs

Contig assembly is the first stage that most assemblers solve when reconstructing a genome from a set of reads. Its output consists of contigs -- a set of strings that are promised to appear in any genome that could have generated the reads. From the introduction of contigs 20 years ago, assemblers have tried to obtain longer and longer contigs, but the following question was never solved: given a genome graph $G$ (e.g. a de Bruijn, or a string graph), what are all the strings that can be safely reported from $G$ as contigs? In this paper we finally answer this question, and also give a polynomial time algorithm to find them. Our experiments show that these strings, which we call omnitigs, are 66% to 82% longer on average than the popular unitigs, and 29% of dbSNP locations have more neighbors in omnitigs than in unitigs.Comment: Full version of the paper in the proceedings of RECOMB 201

Effect of a multidisciplinary stress treatment programme on the return to work rate for persons with work-related stress. A non-randomized controlled study from a stress clinic

<p>Abstract</p> <p>Background</p> <p>In recent years an increasing number of patients have been referred to the medical sector with stress symptoms. Moreover, these conditions imply increased sickness absence. This indicates a need for treatment programmes in general medical practice. The aim of this study was to test the effect of a multidisciplinary stress treatment programme on the return to work (RTW) rate in persons with work-related stress and establish predictive factors for this outcome.</p> <p>Methods</p> <p>During a two-year period 63 out of 73 referrals to the Stress Clinic (a section of a Clinic of Occupational Medicine) completed a stress treatment programme consisted of the following:</p> <p>1) Identification of relevant stressors. 2. Changing the coping strategies of the participants. 3. Evaluating/changes in participant workload and tasks. 4. Relaxation techniques. 5. Physical exercise. 6. Psychiatric evaluation when indicated by depression test score.</p> <p>On average each patient attended six one-hour sessions over the course of four months.</p> <p>A group of 34 employees referred to the Clinic of Occupational Medicine by their general practitioners served as a control group. Each participant had a one-hour consultation at baseline and after four months. A specialist in occupational medicine carried out all sessions.</p> <p>Return To Work (RTW), defined as having a job and not being on sick leave at the census, was used as outcome measure four months after baseline, and after one and two years.</p> <p>Results</p> <p>The level of sick leave in the stress treatment group dropped from 52% to 16% during the first four months of follow-up and remained stable. In the control group, the reduction in sick leave was significantly smaller, ranging from 48% at baseline to 27% after four months and 24% after one year. No statistically significant difference between the two groups was observed after one and two years. Age below 50 years and being a manager increased the odds ratio for RTW after one and two years, while gender and depression had no predictive value.</p> <p>Conclusions</p> <p>The stress treatment programme showed a significant effect on the return to work rate. The stress treatment programme seems feasible for general practitioners.</p> <p>Trial Registration</p> <p>ISRCTN04354658</p

Mining the Gene Wiki for functional genomic knowledge

<p>Abstract</p> <p>Background</p> <p>Ontology-based gene annotations are important tools for organizing and analyzing genome-scale biological data. Collecting these annotations is a valuable but costly endeavor. The Gene Wiki makes use of Wikipedia as a low-cost, mass-collaborative platform for assembling text-based gene annotations. The Gene Wiki is comprised of more than 10,000 review articles, each describing one human gene. The goal of this study is to define and assess a computational strategy for translating the text of Gene Wiki articles into ontology-based gene annotations. We specifically explore the generation of structured annotations using the Gene Ontology and the Human Disease Ontology.</p> <p>Results</p> <p>Our system produced 2,983 candidate gene annotations using the Disease Ontology and 11,022 candidate annotations using the Gene Ontology from the text of the Gene Wiki. Based on manual evaluations and comparisons to reference annotation sets, we estimate a precision of 90-93% for the Disease Ontology annotations and 48-64% for the Gene Ontology annotations. We further demonstrate that this data set can systematically improve the results from gene set enrichment analyses.</p> <p>Conclusions</p> <p>The Gene Wiki is a rapidly growing corpus of text focused on human gene function. Here, we demonstrate that the Gene Wiki can be a powerful resource for generating ontology-based gene annotations. These annotations can be used immediately to improve workflows for building curated gene annotation databases and knowledge-based statistical analyses.</p

Dictyostelium discoideum as a Model to Study Inositol Polyphosphates and Inorganic Polyphosphate

The yeast Saccharomyces cerevisiae has given us much information on the metabolism and function of inositol polyphosphates and inorganic polyphosphate. To expand our knowledge of the metabolic as well as functional connections between inositol polyphosphates and inorganic polyphosphate, we have refined and developed techniques to extract and analyze these molecules in a second eukaryotic experimental model, the amoeba Dictyostelium discoideum. This amoeba, possessing a well-defined developmental program, is ideal to study physiological changes in the levels of inositol polyphosphates and inorganic polyphosphate, since levels of both molecules increase at late stages of development. We detail here the methods used to extract inositol polyphosphates using perchloric acid and inorganic polyphosphate using acidic phenol. We also present the postextraction procedures to visualize and quantify these molecules by polyacrylamide gel electrophoresis and by malachite green assay

Population Structure as Revealed by mtDNA and Microsatellites in Northern Fur Seals, Callorhinus ursinus, throughout Their Range

Background: The northern fur seal (Callorhinus ursinus; NFS) is a widely distributed pinniped that has been shown to exhibit a high degree of philopatry to islands, breeding areas on an island, and even to specific segments of breeding areas. This level of philopatry could conceivably lead to highly genetically divergent populations. However, northern fur seals have the potential for dispersal across large distances and have experienced repeated rapid population expansions following glacial retreat and the more recent cessation of intensive harvest pressure. Methodology/Principal Findings: Using microsatellite and mitochondrial loci, we examined population structure in NFS throughout their range. We found only weak population genetic structure among breeding islands including significant FST and W ST values between eastern and western Pacific islands. Conclusions: We conclude that insufficient time since rapid population expansion events (both post glacial and following the cessation of intense harvest pressure) mixed with low levels of contemporary migration have resulted in an absence of genetic structure across the entire northern fur seal range

Using the realized relationship matrix to disentangle confounding factors for the estimation of genetic variance components of complex traits

Background: In the analysis of complex traits, genetic effects can be confounded with non-genetic effects, especially when using full-sib families. Dominance and epistatic effects are typically confounded with additive genetic and non-genetic effects. This confounding may cause the estimated genetic variance components to be inaccurate and biased

The Cluster Variation Method for Efficient Linkage Analysis on Extended Pedigrees

BACKGROUND: Computing exact multipoint LOD scores for extended pedigrees rapidly becomes infeasible as the number of markers and untyped individuals increase. When markers are excluded from the computation, significant power may be lost. Therefore accurate approximate methods which take into account all markers are desirable. METHODS: We present a novel method for efficient estimation of LOD scores on extended pedigrees. Our approach is based on the Cluster Variation Method, which deterministically estimates likelihoods by performing exact computations on tractable subsets of variables (clusters) of a Bayesian network. First a distribution over inheritances on the marker loci is approximated with the Cluster Variation Method. Then this distribution is used to estimate the LOD score for each location of the trait locus. RESULTS: First we demonstrate that significant power may be lost if markers are ignored in the multi-point analysis. On a set of pedigrees where exact computation is possible we compare the estimates of the LOD scores obtained with our method to the exact LOD scores. Secondly, we compare our method to a state of the art MCMC sampler. When both methods are given equal computation time, our method is more efficient. Finally, we show that CVM scales to large problem instances. CONCLUSION: We conclude that the Cluster Variation Method is as accurate as MCMC and generally is more efficient. Our method is a promising alternative to approaches based on MCMC sampling

Defending the genome from the enemy within:mechanisms of retrotransposon suppression in the mouse germline

The viability of any species requires that the genome is kept stable as it is transmitted from generation to generation by the germ cells. One of the challenges to transgenerational genome stability is the potential mutagenic activity of transposable genetic elements, particularly retrotransposons. There are many different types of retrotransposon in mammalian genomes, and these target different points in germline development to amplify and integrate into new genomic locations. Germ cells, and their pluripotent developmental precursors, have evolved a variety of genome defence mechanisms that suppress retrotransposon activity and maintain genome stability across the generations. Here, we review recent advances in understanding how retrotransposon activity is suppressed in the mammalian germline, how genes involved in germline genome defence mechanisms are regulated, and the consequences of mutating these genome defence genes for the developing germline

Limits on WWZ and WW\gamma couplings from p\bar{p}\to e\nu jj X events at \sqrt{s} = 1.8 TeV

We present limits on anomalous WWZ and WW-gamma couplings from a search for WW and WZ production in p-bar p collisions at sqrt(s)=1.8 TeV. We use p-bar p -> e-nu jjX events recorded with the D0 detector at the Fermilab Tevatron Collider during the 1992-1995 run. The data sample corresponds to an integrated luminosity of 96.0+-5.1 pb^(-1). Assuming identical WWZ and WW-gamma coupling parameters, the 95% CL limits on the CP-conserving couplings are -0.33<lambda<0.36 (Delta-kappa=0) and -0.43<Delta-kappa<0.59 (lambda=0), for a form factor scale Lambda = 2.0 TeV. Limits based on other assumptions are also presented.Comment: 11 pages, 2 figures, 2 table