Reference-free detection of isolated SNPs

International audienceDetecting Single Nucleotide Polymorphisms (SNPs) between genomes is becoming a routine task with Next Generation Sequencing. Generally, SNP detection methods use a reference genome. As non-model organisms are increasingly investigated, the need for reference-free methods has been amplified. Most of the existing reference-free methods have fundamental limitations: they can only call SNPs between exactly two datasets, and/or they require a prohibitive amount of computational resources. The method we propose, DISCOSNP, detects both heterozygous and homozygous isolated SNPs from any number of read datasets, without a reference genome, and with very low memory and time footprints (billions of reads can be analyzed with a standard desktop computer). To facilitate downstream genotyping analyses, DISCOSNP ranks predictions and outputs quality and coverage per allele. Compared to finding isolated SNPs using a state-of-the-art assembly and mapping approach, DISCOSNP requires significantly less computational resources, shows similar precision/recall values, and highly ranked predictions are less likely to be false positives. An experimental validation was conducted on an arthropod species (the tick Ixodes ricinus) on which de novo sequencing was performed. Among the predicted SNPs that were tested, 96% were successfully genotyped and truly exhibited polymorphism

Transradial versus transfemoral approach for percutaneous coronary intervention in cardiogenic shock: A radial-first centre experience and meta-analysis of published studies

SummaryBackgroundThe transradial approach for percutaneous coronary intervention (PCI) is associated with a better outcome in myocardial infarction (MI), but patients with cardiogenic shock (CS) were excluded from most trials.AimsTo compare outcomes of PCI for MI-related CS via the transradial versus transfemoral approach.MethodsA prospective cohort of 101 consecutive patients admitted for PCI for MI-related CS were treated via the transradial (n=74) or transfemoral (n=27) approach. Cox proportional hazards models adjusted for prespecified variables and a propensity score for approach were used to compare mortality, death/MI/stroke and bleeding between the two groups. A complementary meta-analysis of six studies was also performed.ResultsPatients in the transradial group were younger (P=0.039), more often male (P=0.002) and had lower GRACE and CRUSADE scores (P=0.003 and 0.001, respectively) and rates of cardiac arrest before PCI (P=0.009) and mechanical ventilation (P=0.006). Rates of PCI success were similar. At a mean follow-up of 756 days, death occurred in 40 (54.1%) patients in the transradial group versus 22 (81.5%) in the transfemoral group (adjusted hazard ratio [HR]: 0.49, 95% confidence interval [CI] 0.28–0.84; P=0.012). The transradial approach was associated with reduced rates of death/MI/stroke (adjusted HR: 0.53, 95%CI: 0.31–0.91; P=0.02) and major bleeding (adjusted HR: 0.34, 95%CI: 0.13–0.87; P=0.02). The meta-analysis confirmed the benefit of transradial access in terms of mortality (relative risk [RR]: 0.63, 95%CI: 0.58–0.68) and major bleeding (RR: 0.43, 95%CI: 0.32–0.59).ConclusionThe transradial approach in the setting of PCI for ischaemic CS is associated with a dramatic reduction in mortality, ischaemic and bleeding events, and should be preferred to the transfemoral approach in radial expert centres

Transradial versus transfemoral approach for percutaneous coronary intervention in cardiogenic shock: A radial-first centre experience and meta-analysis of published studies

SummaryBackgroundThe transradial approach for percutaneous coronary intervention (PCI) is associated with a better outcome in myocardial infarction (MI), but patients with cardiogenic shock (CS) were excluded from most trials.AimsTo compare outcomes of PCI for MI-related CS via the transradial versus transfemoral approach.MethodsA prospective cohort of 101 consecutive patients admitted for PCI for MI-related CS were treated via the transradial (n=74) or transfemoral (n=27) approach. Cox proportional hazards models adjusted for prespecified variables and a propensity score for approach were used to compare mortality, death/MI/stroke and bleeding between the two groups. A complementary meta-analysis of six studies was also performed.ResultsPatients in the transradial group were younger (P=0.039), more often male (P=0.002) and had lower GRACE and CRUSADE scores (P=0.003 and 0.001, respectively) and rates of cardiac arrest before PCI (P=0.009) and mechanical ventilation (P=0.006). Rates of PCI success were similar. At a mean follow-up of 756 days, death occurred in 40 (54.1%) patients in the transradial group versus 22 (81.5%) in the transfemoral group (adjusted hazard ratio [HR]: 0.49, 95% confidence interval [CI] 0.28–0.84; P=0.012). The transradial approach was associated with reduced rates of death/MI/stroke (adjusted HR: 0.53, 95%CI: 0.31–0.91; P=0.02) and major bleeding (adjusted HR: 0.34, 95%CI: 0.13–0.87; P=0.02). The meta-analysis confirmed the benefit of transradial access in terms of mortality (relative risk [RR]: 0.63, 95%CI: 0.58–0.68) and major bleeding (RR: 0.43, 95%CI: 0.32–0.59).ConclusionThe transradial approach in the setting of PCI for ischaemic CS is associated with a dramatic reduction in mortality, ischaemic and bleeding events, and should be preferred to the transfemoral approach in radial expert centres

Coronary-Pulmonary Fistulas Involving All Three Major Coronary Arteries Co-Existing With Myocardial Infarction

We report the case of a man who presented with acute anterior myocardial infarction and in whom the coronary angiogram showed tight stenosis of the left anterior descending coronary artery and the right coronary artery associated with substantial coronary-pulmonary fistulas involving all three major coronary arteries. We discuss the possible links between coronary artery fistulas and myocardial infarction

Colib'read on galaxy : a tools suite dedicated to biological information extraction from raw NGS reads

Background: With next-generation sequencing (NGS) technologies, the life sciences face a deluge of raw data. Classical analysis processes for such data often begin with an assembly step, needing large amounts of computing resources, and potentially removing or modifying parts of the biological information contained in the data. Our approach proposes to focus directly on biological questions, by considering raw unassembled NGS data, through a suite of six command-line tools. Findings: Dedicated to 'whole-genome assembly-free' treatments, the Colib'read tools suite uses optimized algorithms for various analyses of NGS datasets, such as variant calling or read set comparisons. Based on the use of a de Bruijn graph and bloom filter, such analyses can be performed in a few hours, using small amounts of memory. Applications using real data demonstrate the good accuracy of these tools compared to classical approaches. To facilitate data analysis and tools dissemination, we developed Galaxy tools and tool shed repositories. Conclusions: With the Colib'read Galaxy tools suite, we enable a broad range of life scientists to analyze raw NGS data. More importantly, our approach allows the maximum biological information to be retained in the data, and uses a very low memory footprint.Peer reviewe

Machine Learning Patterns for Neuroimaging-Genetic Studies in the Cloud

International audienceBrain imaging is a natural intermediate phenotype to understand the link between genetic information and behavior or brain pathologies risk factors. Massive efforts have been made in the last few years to acquire high-dimensional neuroimaging and genetic data on large cohorts of subjects. The statistical analysis of such data is carried out with increasingly sophisticated techniques and represents a great computational challenge. Fortunately, increasing computational power in distributed architectures can be harnessed, if new neuroinformatics infrastructures are designed and training to use these new tools is provided. Combining a MapReduce framework (TomusBLOB) with machine learning algorithms (Scikit-learn library), we design a scalable analysis tool that can deal with non-parametric statistics on high-dimensional data. End-users describe the statistical procedure to perform and can then test the model on their own computers before running the very same code in the cloud at a larger scale. We illustrate the potential of our approach on real data with an experiment showing how the functional signal in subcortical brain regions can be significantly fit with genome-wide genotypes. This experiment demonstrates the scalability and the reliability of our framework in the cloud with a two weeks deployment on hundreds of virtual machines

Close 3D proximity of evolutionary breakpoints argues for the notion of spatial synteny

<p>Abstract</p> <p>Background</p> <p>Folding and intermingling of chromosomes has the potential of bringing close to each other loci that are very distant genomically or even on different chromosomes. On the other hand, genomic rearrangements also play a major role in the reorganisation of loci proximities. Whether the same loci are involved in both mechanisms has been studied in the case of somatic rearrangements, but never from an evolutionary standpoint.</p> <p>Results</p> <p>In this paper, we analysed the correlation between two datasets: (i) whole-genome chromatin contact data obtained in human cells using the Hi-C protocol; and (ii) a set of breakpoint regions resulting from evolutionary rearrangements which occurred since the split of the human and mouse lineages. Surprisingly, we found that two loci distant in the human genome but adjacent in the mouse genome are significantly more often observed in close proximity in the human nucleus than expected. Importantly, we show that this result holds for loci located on the same chromosome regardless of the genomic distance separating them, and the signal is stronger in gene-rich and open-chromatin regions.</p> <p>Conclusions</p> <p>These findings strongly suggest that part of the 3D organisation of chromosomes may be conserved across very large evolutionary distances. To characterise this phenomenon, we propose to use the notion of spatial synteny which generalises the notion of genomic synteny to the 3D case.</p

Differentiating Lithogenic Supplies, Water Mass Transport, and Biological Processes On and Off the Kerguelen Plateau Using Rare Earth Element Concentrations and Neodymium Isotopic Compositions

Distributions of dissolved rare earth element (REE) concentrations and neodymium isotopic compositions (expressed as εNd) of seawater over and off the Kerguelen Plateau in the Southern Ocean are presented. The sampling took place during the austral spring bloom in October–November 2011 (KEOPS2 project, GEOTRACES process study) and aimed to further the investigations of the KEOPS1 austral summer study in terms of sources and transport of lithogenic material, and to investigate the impact of local biogeochemical cycles on the REE distributions. The REE signature of the coastal eastern Kerguelen Islands waters was characterized by negative europium anomalies (Eu/Eu*) and negative εNd in filtered samples. By contrast, the unfiltered sample showed a positive Eu/Eu* and more radiogenic εNd. These distinct signatures could reflect either differential dissolution of the local flood basalt minerals or differential leaching of local trachyte veins. The dissolved Kerguelen coastal REE patterns differ from those observed close to Heard Island, these latter featuring a positive Eu/Eu* and a less radiogenic εNd (Zhang et al., 2008). These differences enabled us to trace the transport of waters (tagged by the Kerguelen REE signature) 200 km downstream from the coastal area, north of the Polar Front. Northward transport of the central Plateau shallow waters, enriched by both local vertical supplies and lateral advection of inputs from Heard Island, was also evident. However, the transport of Kerguelen inputs southeastward across the Polar Front could not be discerned (possibly as a result of rapid dilution or scavenging of REE signatures), although evidence for such transport was found previously using Ra isotopes (Sanial et al., 2015). Comparison of the REE patterns at stations sampled prior, during and at the demise of the bloom revealed diverse fractionations, including production of significant lanthanum and europium anomalies, which are tentatively ascribed to chemical reactions with various inorganic and biogenic phases, including surface coatings, barite crystals, and biogenic silica

Search for supersymmetry in events with opposite-sign dileptons and missing transverse energy using an artificial neural network

In this paper, a search for supersymmetry (SUSY) is presented in events with two opposite-sign isolated leptons in the final state, accompanied by hadronic jets and missing transverse energy. An artificial neural network is employed to discriminate possible SUSY signals from a standard model background. The analysis uses a data sample collected with the CMS detector during the 2011 LHC run, corresponding to an integrated luminosity of 4.98  fb-1 of proton-proton collisions at the center-of-mass energy of 7 TeV. Compared to other CMS analyses, this one uses relaxed criteria on missing transverse energy (E̸T>40  GeV) and total hadronic transverse energy (HT>120  GeV), thus probing different regions of parameter space. Agreement is found between standard model expectation and observations, yielding limits in the context of the constrained minimal supersymmetric standard model and on a set of simplified model