Silvia Liverani

Orchestrated transcription of biological processes in the marine picoeukaryote Ostreococcus exposed to light/dark cycles.

BackgroundPicoeukaryotes represent an important, yet poorly characterized component of marine phytoplankton. The recent genome availability for two species of Ostreococcus and Micromonas has led to the emergence of picophytoplankton comparative genomics. Sequencing has revealed many unexpected features about genome structure and led to several hypotheses on Ostreococcus biology and physiology. Despite the accumulation of genomic data, little is known about gene expression in eukaryotic picophytoplankton.ResultsWe have conducted a genome-wide analysis of gene expression in Ostreococcus tauri cells exposed to light/dark cycles (L/D). A Bayesian Fourier Clustering method was implemented to cluster rhythmic genes according to their expression waveform. In a single L/D condition nearly all expressed genes displayed rhythmic patterns of expression. Clusters of genes were associated with the main biological processes such as transcription in the nucleus and the organelles, photosynthesis, DNA replication and mitosis.ConclusionsLight/Dark time-dependent transcription of the genes involved in the main steps leading to protein synthesis (transcription basic machinery, ribosome biogenesis, translation and aminoacid synthesis) was observed, to an unprecedented extent in eukaryotes, suggesting a major input of transcriptional regulations in Ostreococcus. We propose that the diurnal co-regulation of genes involved in photoprotection, defence against oxidative stress and DNA repair might be an efficient mechanism, which protects cells against photo-damage thereby, contributing to the ability of O. tauri to grow under a wide range of light intensities.

Analysing the health effects of simultaneous exposure to physical and chemical properties of airborne particles

Background Airborne particles are a complex mix of organic and inorganic compounds, with a range of physical and chemical properties. Estimation of how simultaneous exposure to air particles affects the risk of adverse health response represents a challenge for scientific research and air quality management. In this paper, we present a Bayesian approach that can tackle this problem within the framework of time series analysis. Methods We used Dirichlet process mixture models to cluster time points with similar multipollutant and response profiles, while adjusting for seasonal cycles, trends and temporal components. Inference was carried out via Markov Chain Monte Carlo methods. We illustrated our approach using daily data of a range of particle metrics and respiratory mortality for London (UK) 2002–2005. To better quantify the average health impact of these particles, we measured the same set of metrics in 2012, and we computed and compared the posterior predictive distributions of mortality under the exposure scenario in 2012 vs 2005. Results The model resulted in a partition of the days into three clusters. We found a relative risk of 1.02 (95% credible intervals (CI): 1.00, 1.04) for respiratory mortality associated with days characterised by high posterior estimates of non-primary particles, especially nitrate and sulphate. We found a consistent reduction in the airborne particles in 2012 vs 2005 and the analysis of the posterior predictive distributions of respiratory mortality suggested an average annual decrease of − 3.5% (95% CI: − 0.12%, − 5.74%). Conclusions We proposed an effective approach that enabled the better understanding of hidden structures in multipollutant health effects within time series analysis. It allowed the identification of exposure metrics associated with respiratory mortality and provided a tool to assess the changes in health effects from various policies to control the ambient particle matter mixtures.

Modeling spatial effects of PM2.5 on term low birth weight in Los Angeles County

Air pollution epidemiological studies suggest that elevated exposure to fine particulate matter (PM2.5) is associated with higher prevalence of term low birth weight (TLBW). Previous studies have generally assumed the exposure-response of PM2.5 on TLBW to be the same throughout a large geographical area. Health effects related to PM2.5 exposures, however, may not be uniformly distributed spatially, creating a need for studies that explicitly investigate the spatial distribution of the exposure-response relationship between individual-level exposure to PM2.5 and TLBW. Here, we examine the overall and spatially varying exposure-response relationship between PM2.5 and TLBW throughout urban Los Angeles (LA) County, California. We estimated PM2.5 from a combination of land use regression (LUR), aerosol optical depth from remote sensing, and atmospheric modeling techniques. Exposures were assigned to LA County individual pregnancies identified from electronic birth certificates between the years 1995-2006 (N=1,359,284) provided by the California Department of Public Health. We used a single pollutant multivariate logistic regression model, with multilevel spatially structured and unstructured random effects set in a Bayesian framework to estimate global and spatially varying pollutant effects on TLBW at the census tract level. Overall, increased PM2.5 level was associated with higher prevalence of TLBW county-wide. The spatial random effects model, however, demonstrated that the exposure-response for PM2.5 and TLBW was not uniform across urban LA County. Rather, the magnitude and certainty of the exposure-response estimates for PM2.5 on log odds of TLBW were greatest in the urban core of Central and Southern LA County census tracts. These results suggest that the effects may be spatially patterned, and that simply estimating global pollutant effects obscures disparities suggested by spatial patterns of effects. Studies that incorporate spatial multilevel modeling with random coefficients allow us to identify areas where air pollutant effects on adverse birth outcomes may be most severe and policies to further reduce air pollution might be most effective.

Multi-pollutant exposure profiles associated with term low birth weight in Los Angeles County

Research indicates that multiple outdoor air pollutants and adverse neighborhood conditions are spatially correlated. Yet health risks associated with concurrent exposure to air pollution mixtures and clustered neighborhood factors remain underexplored. Statistical models to assess the health effects from pollutant mixtures remain limited, due to problems of collinearity between pollutants and area-level covariates, and increases in covariate dimensionality. Here we identify pollutant exposure profiles and neighborhood contextual profiles within Los Angeles (LA) County. We then relate these profiles with term low birth weight (TLBW). We used land use regression to estimate NO2, NO, and PM2.5 concentrations averaged over census block groups to generate pollutant exposure profile clusters and census block group-level contextual profile clusters, using a Bayesian profile regression method. Pollutant profile cluster risk estimation was implemented using a multilevel hierarchical model, adjusting for individual-level covariates, contextual profile cluster random effects, and modeling of spatially structured and unstructured residual error. Our analysis found 13 clusters of pollutant exposure profiles. Correlations between study pollutants varied widely across the 13 pollutant clusters. Pollutant clusters with elevated NO2, NO, and PM2.5 concentrations exhibited increased log odds of TLBW, and those with low PM2.5, NO2, and NO concentrations showed lower log odds of TLBW. The spatial patterning of pollutant cluster effects on TLBW, combined with between-pollutant correlations within pollutant clusters, imply that traffic-related primary pollutants influence pollutant cluster TLBW risks. Furthermore, contextual clusters with the greatest log odds of TLBW had more adverse neighborhood socioeconomic, demographic, and housing conditions. Our data indicate that, while the spatial patterning of high-risk multiple pollutant clusters largely overlaps with adverse contextual neighborhood cluster, both contribute to TLBW while controlling for the other.

A semi-parametric approach to estimate risk functions associated with multi-dimensional exposure profiles: application to smoking and lung cancer

BackgroundA common characteristic of environmental epidemiology is the multi-dimensional aspect of exposure patterns, frequently reduced to a cumulative exposure for simplicity of analysis. By adopting a flexible Bayesian clustering approach, we explore the risk function linking exposure history to disease. This approach is applied here to study the relationship between different smoking characteristics and lung cancer in the framework of a population based case control study.MethodsOur study includes 4658 males (1995 cases, 2663 controls) with full smoking history (intensity, duration, time since cessation, pack-years) from the ICARE multi-centre study conducted from 2001-2007. We extend Bayesian clustering techniques to explore predictive risk surfaces for covariate profiles of interest.ResultsWe were able to partition the population into 12 clusters with different smoking profiles and lung cancer risk. Our results confirm that when compared to intensity, duration is the predominant driver of risk. On the other hand, using pack-years of cigarette smoking as a single summary leads to a considerable loss of information.ConclusionsOur method estimates a disease risk associated to a specific exposure profile by robustly accounting for the different dimensions of exposure and will be helpful in general to give further insight into the effect of exposures that are accumulated through different time patterns.

Sampling from Dirichlet process mixture models with unknown concentration parameter: mixing issues in large data implementations

We consider the question of Markov chain Monte Carlo sampling from a general stick-breaking Dirichlet process mixture model, with concentration parameter

Efficient utility-based clustering over high dimensional partition spaces

\alpha

Modelling collinear and spatially correlated data

α. This paper introduces a Gibbs sampling algorithm that combines the slice sampling approach of Walker (Communications in Statistics - Simulation and Computation 36:45–54, 2007) and the retrospective sampling approach of Papaspiliopoulos and Roberts (Biometrika 95(1):169–186, 2008). Our general algorithm is implemented as efficient open source C++ software, available as an R package, and is based on a blocking strategy similar to that suggested by Papaspiliopoulos (A note on posterior sampling from Dirichlet mixture models, 2008) and implemented by Yau et al. (Journal of the Royal Statistical Society, Series B (Statistical Methodology) 73:37–57, 2011). We discuss the difficulties of achieving good mixing in MCMC samplers of this nature in large data sets and investigate sensitivity to initialisation. We additionally consider the challenges when an additional layer of hierarchy is added such that joint inference is to be made on