Differential expression analysis for sequence count data via mixtures of negative binomials

The recent advent of Next-generation sequencing technologies has revolutionized the way of analyzing the genome. This innovation allows to get deeper information at a lower cost and in less time, and provides data that are discrete measurements. One of the most important applications with these data is the differential analysis, that is investigating if one gene exhibit a different expression level in correspondence of two (or more) biological conditions (such as disease states, treatments received and so on). As for the statistical analysis, the final aim will be statistical testing and for modeling these data the Negative Binomial distribution is considered the most adequate one especially because it allows for "over dispersion". However, the estimation of the dispersion parameter is a very delicate issue because few information are usually available for estimating it. Many strategies have been proposed, but they often result in procedures based on plug-in estimates, and in this thesis we show that this discrepancy between the estimation and the testing framework can lead to uncontrolled first-type errors. We propose a mixture model that allows each gene to share information with other genes that exhibit similar variability. Afterwards, three consistent statistical tests are developed for differential expression analysis. We show that the proposed method improves the sensitivity of detecting differentially expressed genes with respect to the common procedures, since it is the best one in reaching the nominal value for the first-type error, while keeping elevate power. The method is finally illustrated on prostate cancer RNA-seq data.

Multi-pollutants impact on modern cement built heritage

It is well known that the deposition of gaseous pollutants and aerosols plays a major role in causing the deterioration of monuments and built cultural heritage in European cities. Despite of many studies dedicated to the environmental damage of cultural heritage, in case of cement mortars, commonly used in the 20th century architecture, the deterioration due to air multipollutants impact, especially the formation of black crusts, is still not well explored making this issue a challenging area of research. This work centers on cement mortars – environment interactions, focusing on the diagnosis of the damage on the modern built heritage due to air multi-pollutants. For this purpose three sites, exposed to different urban areas in Europe, were selected for sampling and subsequent laboratory analyses: Centennial Hall, Wroclaw (Poland), Chiesa dell'Autostrada del Sole, Florence (Italy), Casa Galleria Vichi, Florence (Italy). The sampling sessions were performed taking into account the height from the ground level and protection from rain run off (sheltered, partly sheltered and exposed areas). The complete characterization of collected damage layer and underlying materials was performed using a range of analytical techniques: optical and scanning electron microscopy, X ray diffractometry, differential and gravimetric thermal analysis, ion chromatography, flash combustion/gas chromatographic analysis, inductively coupled plasma-optical emission spectrometer. The data were elaborated using statistical methods (i.e. principal components analyses) and enrichment factor for cement mortars was calculated for the first time. The results obtained from the experimental activity performed on the damage layers indicate that gypsum, due to the deposition of atmospheric sulphur compounds, is the main damage product at surfaces sheltered from rain run-off at Centennial Hall and Casa Galleria Vichi. By contrast, gypsum has not been identified in the samples collected at Chiesa dell'Autostrada del Sole. This is connected to the restoration works, particularly surface cleaning, regularly performed for the maintenance of the building. Moreover, the results obtained demonstrated the correlation between the location of the building and the composition of the damage layer: Centennial Hall is mainly undergoing to the impact of pollutants emitted from the close coal power stations, whilst Casa Galleria Vichi is principally affected by pollutants from vehicular exhaust in front of the building.