Mixture model with multiple allocations for clustering spatially correlated observations in the analysis of ChIP-Seq data

Model-based clustering is a technique widely used to group a collection of units into mutually exclusive groups. There are, however, situations in which an observation could in principle belong to more than one cluster. In the context of Next-Generation Sequencing (NGS) experiments, for example, the signal observed in the data might be produced by two (or more) different biological processes operating together and a gene could participate in both (or all) of them. We propose a novel approach to cluster NGS discrete data, coming from a ChIP-Seq experiment, with a mixture model, allowing each unit to belong potentially to more than one group: these multiple allocation clusters can be flexibly defined via a function combining the features of the original groups without introducing new parameters. The formulation naturally gives rise to a `zero-inflation group' in which values close to zero can be allocated, acting as a correction for the abundance of zeros that manifest in this type of data. We take into account the spatial dependency between observations, which is described through a latent Conditional Auto-Regressive process that can reflect different dependency patterns. We assess the performance of our model within a simulation environment and then we apply it to ChIP-seq real data.Comment: 25 pages; 3 tables, 6 figure

Recent decreases in fossil-fuel emissions of ethane and methane derived from firn air

Methane and ethane are the most abundant hydrocarbons in the atmosphere and they affect both atmospheric chemistry and climate. Both gases are emitted from fossil fuels and biomass burning, whereas methane (CH(4)) alone has large sources from wetlands, agriculture, landfills and waste water. Here we use measurements in firn (perennial snowpack) air from Greenland and Antarctica to reconstruct the atmospheric variability of ethane (C(2)H(6)) during the twentieth century. Ethane levels rose from early in the century until the 1980s, when the trend reversed, with a period of decline over the next 20 years. We find that this variability was primarily driven by changes in ethane emissions from fossil fuels; these emissions peaked in the 1960s and 1970s at 14-16 teragrams per year (1 Tg = 10(12) g) and dropped to 8-10 Tg  yr(-1) by the turn of the century. The reduction in fossil-fuel sources is probably related to changes in light hydrocarbon emissions associated with petroleum production and use. The ethane-based fossil-fuel emission history is strikingly different from bottom-up estimates of methane emissions from fossil-fuel use, and implies that the fossil-fuel source of methane started to decline in the 1980s and probably caused the late twentieth century slow-down in the growth rate of atmospheric methane

Attaching and effacing (A/E) lesion formation by enteropathogenic E. coli on human intestinal mucosa is dependent on non-LEE effectors

Enteropathogenic E. coli (EPEC) is a human pathogen that causes acute and chronic pediatric diarrhea. The hallmark of EPEC infection is the formation of attaching and effacing (A/E) lesions in the intestinal epithelium. Formation of A/E lesions is mediated by genes located on the pathogenicity island locus of enterocyte effacement (LEE), which encode the adhesin intimin, a type III secretion system (T3SS) and six effectors, including the essential translocated intimin receptor (Tir). Seventeen additional effectors are encoded by genes located outside the LEE, in insertion elements and prophages. Here, using a stepwise approach, we generated an EPEC mutant lacking the entire effector genes (EPEC0) and intermediate mutants. We show that EPEC0 contains a functional T3SS. An EPEC mutant expressing intimin but lacking all the LEE effectors but Tir (EPEC1) was able to trigger robust actin polymerization in HeLa cells and mucin-producing intestinal LS174T cells. However, EPEC1 was unable to form A/E lesions on human intestinal in vitro organ cultures (IVOC). Screening the intermediate mutants for genes involved in A/E lesion formation on IVOC revealed that strains lacking non-LEE effector/s have a marginal ability to form A/E lesions. Furthermore, we found that Efa1/LifA proteins are important for A/E lesion formation efficiency in EPEC strains lacking multiple effectors. Taken together, these results demonstrate the intricate relationships between T3SS effectors and the essential role non-LEE effectors play in A/E lesion formation on mucosal surfaces

Identifying associations between diabetes and acute respiratory distress syndrome in patients with acute hypoxemic respiratory failure: an analysis of the LUNG SAFE database

Background: Diabetes mellitus is a common co-existing disease in the critically ill. Diabetes mellitus may reduce the risk of acute respiratory distress syndrome (ARDS), but data from previous studies are conflicting. The objective of this study was to evaluate associations between pre-existing diabetes mellitus and ARDS in critically ill patients with acute hypoxemic respiratory failure (AHRF). Methods: An ancillary analysis of a global, multi-centre prospective observational study (LUNG SAFE) was undertaken. LUNG SAFE evaluated all patients admitted to an intensive care unit (ICU) over a 4-week period, that required mechanical ventilation and met AHRF criteria. Patients who had their AHRF fully explained by cardiac failure were excluded. Important clinical characteristics were included in a stepwise selection approach (forward and backward selection combined with a significance level of 0.05) to identify a set of independent variables associated with having ARDS at any time, developing ARDS (defined as ARDS occurring after day 2 from meeting AHRF criteria) and with hospital mortality. Furthermore, propensity score analysis was undertaken to account for the differences in baseline characteristics between patients with and without diabetes mellitus, and the association between diabetes mellitus and outcomes of interest was assessed on matched samples. Results: Of the 4107 patients with AHRF included in this study, 3022 (73.6%) patients fulfilled ARDS criteria at admission or developed ARDS during their ICU stay. Diabetes mellitus was a pre-existing co-morbidity in 913 patients (22.2% of patients with AHRF). In multivariable analysis, there was no association between diabetes mellitus and having ARDS (OR 0.93 (0.78-1.11); p = 0.39), developing ARDS late (OR 0.79 (0.54-1.15); p = 0.22), or hospital mortality in patients with ARDS (1.15 (0.93-1.42); p = 0.19). In a matched sample of patients, there was no association between diabetes mellitus and outcomes of interest. Conclusions: In a large, global observational study of patients with AHRF, no association was found between diabetes mellitus and having ARDS, developing ARDS, or outcomes from ARDS. Trial registration: NCT02010073. Registered on 12 December 2013

Corrigendum to "controls on the movement and composition of firn air at the West Antarctic ice sheet divide"

No abstract available

Post-coring entrapment of modern air in polar ice: Evidence from CFC-12 measurements in Antarctic firn air and shallow ice cores

This study is a comparison of CFC-12 (CCl2F2) measurements in firn air and ice core samples from three Antarctic sites: South Pole, West Antarctic Ice Sheet Divide (79.46°S, 112.13°W), and Siple Dome (81.65°S, 148.81°W). CFC-12 is a synthetic chlorofluorocarbon manufactured during the mid-late 20th century for use as a refrigerant and an aerosol spray propellant. Its atmospheric history is well established with agreement among instrumental time series measurements and industry-reported production data [Walker et al., 2000], the distribution of dissolved CFC-12 in the oceans [e.g. Weiss et al., 1985], and firn air measurements [Butler et al., 1999]. The atmospheric history indicates that there was no measureable CFC-12 in the atmosphere prior to the 1940’s. The firn air CFC-12 profiles are consistent with the known atmospheric history of this gas. In contrast, the air in ice core samples collected near the close-off depth exhibit anomalously high CFC-12 levels. We propose that this is due to entrapment of modern air in open pores that close after drilling, resulting in elevated CFC-12 mixing ratios. These results demonstrate how the composition of air trapped in shallow ice cores can be altered during the post-drilling period through purely physical processes. Comparison of firn air and ice core bubble composition is one of the commonly used tools for studying the bubble close-off process. The post-drilling entrapment process detected in this study represents a potential complication for such investigations

Post-coring entrapment of modern air in polar ice: Evidence from CFC-12 measurements in Antarctic firn air and shallow ice cores

This study is a comparison of CFC-12 (CCl2F2) measurements in firn air and ice core samples from three Antarctic sites: South Pole, West Antarctic Ice Sheet Divide (79.46°S, 112.13°W), and Siple Dome (81.65°S, 148.81°W). CFC-12 is a synthetic chlorofluorocarbon manufactured during the mid-late 20th century for use as a refrigerant and an aerosol spray propellant. Its atmospheric history is well established with agreement among instrumental time series measurements and industry-reported production data [Walker et al., 2000], the distribution of dissolved CFC-12 in the oceans [e.g. Weiss et al., 1985], and firn air measurements [Butler et al., 1999]. The atmospheric history indicates that there was no measureable CFC-12 in the atmosphere prior to the 1940’s. The firn air CFC-12 profiles are consistent with the known atmospheric history of this gas. In contrast, the air in ice core samples collected near the close-off depth exhibit anomalously high CFC-12 levels. We propose that this is due to entrapment of modern air in open pores that close after drilling, resulting in elevated CFC-12 mixing ratios. These results demonstrate how the composition of air trapped in shallow ice cores can be altered during the post-drilling period through purely physical processes. Comparison of firn air and ice core bubble composition is one of the commonly used tools for studying the bubble close-off process. The post-drilling entrapment process detected in this study represents a potential complication for such investigations