Functional data analysis approaches for genotype-phenotype association studies from next-generation sequencing

Next-generation DNA sequencing platforms can effectively detect the entire spectrum of genomic variation and is emerging to be a major tool for systematic exploration of the universe of variants and interactions in the entire genome. However, the data produced by next-generation sequencing technologies will suffer from three basic problems: sequence errors, assembly errors, and missing data. Current statistical methods for genetic analysis are well suited for detecting the association of common variants, but are less suitable to rare variants. This raises great challenge for sequence-based genetic studies of complex diseases.^ This research dissertation utilized genome continuum model as a general principle, and stochastic calculus and functional data analysis as tools for developing novel and powerful statistical methods for next generation of association studies of both qualitative and quantitative traits in the context of sequencing data, which finally lead to shifting the paradigm of association analysis from the current locus-by-locus analysis to collectively analyzing genome regions.^ In this project, the functional principal component (FPC) methods coupled with high-dimensional data reduction techniques will be used to develop novel and powerful methods for testing the associations of the entire spectrum of genetic variation within a segment of genome or a gene regardless of whether the variants are common or rare.^ The classical quantitative genetics suffer from high type I error rates and low power for rare variants. To overcome these limitations for resequencing data, this project used functional linear models with scalar response to develop statistics for identifying quantitative trait loci (QTLs) for both common and rare variants. To illustrate their applications, the functional linear models were applied to five quantitative traits in Framingham heart studies. ^ This project proposed a novel concept of gene-gene co-association in which a gene or a genomic region is taken as a unit of association analysis and used stochastic calculus to develop a unified framework for testing the association of multiple genes or genomic regions for both common and rare alleles. The proposed methods were applied to gene-gene co-association analysis of psoriasis in two independent GWAS datasets which led to discovery of networks significantly associated with psoriasis.^

Social Network Analysis and Qualitative Comparative Analysis: Their mutual benefit for the explanation of policy network structures

By switching the level of analysis and aggregating data from the micro-level of individual cases to the macro-level, quantitative data can be analysed within a more case-based approach. This paper presents such an approach in two steps: In a first step, it discusses the combination of Social Network Analysis (SNA) and Qualitative Comparative Analysis (QCA) in a sequential mixed-methods research design. In such a design, quantitative social network data on individual cases and their relations at the micro-level are used to describe the structure of the network that these cases constitute at the macro-level. Different network structures can then be compared by QCA. This strategy allows adding an element of potential causal explanation to SNA, while SNA-indicators allow for a systematic description of the cases to be compared by QCA. Because mixing methods can be a promising, but also a risky endeavour, the methodological part also discusses the possibility that underlying assumptions of both methods could clash. In a second step, the research design presented beforehand is applied to an empirical study of policy network structures in Swiss politics. Through a comparison of 11 policy networks, causal paths that lead to a conflictual or consensual policy network structure are identified and discussed. The analysis reveals that different theoretical factors matter and that multiple conjunctural causation is at work. Based on both the methodological discussion and the empirical application, it appears that a combination of SNA and QCA can represent a helpful methodological design for social science research and a possibility of using quantitative data with a more case-based approach.

A tale of two analyses: the use of archived qualitative data

This article provides a unique contribution to the debates about archived qualitative data by drawing on two uses of the same data - British Migrants in Spain: the Extent and Nature of Social Integration, 2003-2005 - by Jones (2009) and Oliver and O'Reilly (2010), both of which utilise Bourdieu's concepts analytically and produce broadly similar findings. We argue that whilst the insights and experiences of those researchers directly involved in data collection are important resources for developing contextual knowledge used in data analysis, other kinds of critical distance can also facilitate credible data use. We therefore challenge the assumption that the idiosyncratic relationship between context, reflexivity and interpretation limits the future use of data. Moreover, regardless of the complex genealogy of the data itself, given the number of contingencies shaping the qualitative research process and thus the potential for partial or inaccurate interpretation, contextual familiarity need not be privileged over other aspects of qualitative praxis such as sustained theoretical insight, sociological imagination and methodological rigour. © Sociological Research Online, 1996-2012.

Identifying the configurational paths to innovation in SMEs:a fuzzy-set qualitative comparative analysis

Using fuzzy-set qualitative comparative analysis (fsQCA), this study investigates the conditions leading to a higher level of innovation. More specifically, the study explores the impact of inter-organisational knowledge transfer networks and organisations' internal capabilities on different types of innovation in Small to Medium size Enterprises (SMEs) in the high-tech sector. A survey instrument was used to collect data from a sample of UK SMEs. The findings show that although individual factors are important, there is no need for a company to perform well in all the areas. The fsQCA, which enables the examination of the impacts of different combinations of factors, reveals that there are a number of paths to achieve better incremental and radical innovation performance. Companies need to choose the one that is closest to their abilities and fits best with their resources.

Barriers to working with people affected by cancer: Preliminary qualitative data from a mixed methods exploration of practitioner perspectives in nutritional therapy

Introduction: Cancer is a leading cause of death worldwide. Nutrition may affect occurrence, recurrence and survival rates and many cancer patients and survivors seek individualized nutrition advice. Appropriately skilled nutritional therapy (NT) practitioners may be well-placed to safely provide this advice, but little is known of their perspectives on working with people affected by cancer. This mixed-methods study seeks to explore their views on training, barriers to practice, use of evidence, and other resources, to support the development of safe evidence-based practice. Preliminary data on barriers to practice are reported here. Methods: Two cohorts of NT practitioners were recruited from all UK registered NT practitioners, by an on-line anonymous survey. 84 cancer practitioners (CP) and 165 non-cancer practitioners (NCP) were recruited. Mixed quantitative and qualitative data was collected by the survey. Content analysis was used to analyze qualitative data on the use of evidence, barriers to practice and perceived needs for working with clients with cancer, for further exploration using interviews and focus groups. Preliminary results: For the NCP cohort, exploring themes of perceived barriers to working with people affected by cancer suggested that perceived complexity, risk and need for caution in this area of practice were important barriers. Insufficient specialist knowledge and skills also emerged as barriers. Some NCPs perceived opposition from medical practitioners and other mainstream healthcare professions as an obstacle to starting cancer practice. To overcome these barriers, specialist training emerged as most important. For the CP cohort, in exploring the skills they considered enabled them to undertake cancer work, specialist clinical and technical knowledge emerged strongly. Only 10% CP participants did not want more work with people affected by cancer. 10% CPs reported some NHS referrals, whereas most received clients by self-referral or from other practitioners. When considering barriers that impede their cancer practice, the dominant categories for CPs were hostility or opposition by mainstream oncology professionals, and lack of dialogue and engagement with them. To overcome these barriers, CPs desired engagement with oncology professionals and recognized specialist cancer NT training. For both NCPs and CPs, evidence resources, practice guidelines and practitioner support networks also emerged as potential enablers to cancer practice. Conclusions: This is the first detailed exploration of NT practitioners’ perceived barriers to working with people affected by cancer. Acquiring specialist skills and knowledge appears important to enable NCPs to start cancer work, and for CPs with these skills, the perceived barriers appear foremost in the relationship with mainstream cancer professionals. Further exploration of these themes, and other NT practitioner perspectives on working with people affected by cancer, is underway. This work will inform and support the development of professional practice, training and other resources.

Equational Reasoning as a Tool for Data Analysis

A combination of deductive reasoning, clustering, and inductive learning is given as an example of a hybrid system for exploratory data analysis. Visualization is replaced by a dialogue with the data.

Data analysis in multiple-frequency bioelectrical impedance analysis

The performance of three analytical methods for multiple-frequency bioelectrical impedance analysis (MFBIA) data was assessed. The methods were the established method of Cole and Cole, the newly proposed method of Siconolfi and co-workers and a modification of this procedure. Method performance was assessed from the adequacy of the curve fitting techniques, as judged by the correlation coefficient and standard error of the estimate, and the accuracy of the different methods in determining the theoretical values of impedance parameters describing a set of model electrical circuits. The experimental data were well fitted by all curve-fitting procedures (r = 0.9 with SEE 0.3 to 3.5% or better for most circuit-procedure combinations). Cole-Cole modelling provided the most accurate estimates of circuit impedance values, generally within 1-2% of the theoretical values, followed by the Siconolfi procedure using a sixth-order polynomial regression (1-6% variation). None of the methods, however, accurately estimated circuit parameters when the measured impedances were low (<20 Omega) reflecting the electronic limits of the impedance meter used. These data suggest that Cole-Cole modelling remains the preferred method for the analysis of MFBIA data.

Analyzing the connectivity between regions of interest: An approach based on cluster Granger causality for NRI data analysis

The identification, modeling, and analysis of interactions between nodes of neural systems in the human brain have become the aim of interest of many studies in neuroscience. The complex neural network structure and its correlations with brain functions have played a role in all areas of neuroscience, including the comprehension of cognitive and emotional processing. Indeed, understanding how information is stored, retrieved, processed, and transmitted is one of the ultimate challenges in brain research. In this context, in functional neuroimaging, connectivity analysis is a major tool for the exploration and characterization of the information flow between specialized brain regions. In most functional magnetic resonance imaging (fMRI) studies, connectivity analysis is carried out by first selecting regions of interest (ROI) and then calculating an average BOLD time series (across the voxels in each cluster). Some studies have shown that the average may not be a good choice and have suggested, as an alternative, the use of principal component analysis (PCA) to extract the principal eigen-time series from the ROI(s). In this paper, we introduce a novel approach called cluster Granger analysis (CGA) to study connectivity between ROIs. The main aim of this method was to employ multiple eigen-time series in each ROI to avoid temporal information loss during identification of Granger causality. Such information loss is inherent in averaging (e.g., to yield a single ""representative"" time series per ROI). This, in turn, may lead to a lack of power in detecting connections. The proposed approach is based on multivariate statistical analysis and integrates PCA and partial canonical correlation in a framework of Granger causality for clusters (sets) of time series. We also describe an algorithm for statistical significance testing based on bootstrapping. By using Monte Carlo simulations, we show that the proposed approach outperforms conventional Granger causality analysis (i.e., using representative time series extracted by signal averaging or first principal components estimation from ROIs). The usefulness of the CGA approach in real fMRI data is illustrated in an experiment using human faces expressing emotions. With this data set, the proposed approach suggested the presence of significantly more connections between the ROIs than were detected using a single representative time series in each ROI. (c) 2010 Elsevier Inc. All rights reserved.

Exploratory spatial data analysis techniques for examining urban crime

Regional planners, policy makers and policing agencies all recognize the importance of better understanding the dynamics of crime. Theoretical and application-oriented approaches which provide insights into why and where crimes take place are much sought after. Geographic information systems and spatial analysis techniques, in particular, are proving to be essential or studying criminal activity. However, the capabilities of these quantitative methods continue to evolve. This paper explores the use of geographic information systems and spatial analysis approaches for examining crime occurrence in Brisbane, Australia. The analysis highlights novel capabilities for the analysis of crime in urban regions.

Data analysis model selection for estimating local population size of the Risso’s dolphin (Grampus griseus) in the Azores

27th Annual Conference of the European Cetacean Society. Setúbal, Portugal, 8-10 April 2013.

Exploratory geospatial data analysis using self-organizing maps

Dissertação apresentada como requisito parcial para obtenção do grau de Mestre em Ciência e Sistemas de Informação Geográfica

Acquisition and data analysis related to changes in some forest soils properties after prescribed fire action

Controlled fires in forest areas are frequently used in most Mediterranean countries as a preventive technique to avoid severe wildfires in summer season. In Portugal, this forest management method of fuel mass availability is also used and has shown to be beneficial as annual statistical reports confirm that the decrease of wildfires occurrence have a direct relationship with the controlled fire practice. However prescribed fire can have serious side effects in some forest soil properties. This work shows the changes that occurred in some forest soils properties after a prescribed fire action. The experiments were carried out in soil cover over a natural site of Andaluzitic schist, in Gramelas, Caminha, Portugal, that had not been burn for four years. The composed soil samples were collected from five plots at three different layers (0-3cm, 3-6cm and 6-18cm) during a three-year monitoring period after the prescribed burning. Principal Component Analysis was used to reach the presented conclusions.

Acqusition and data analysis of the eco-efficiency for the establishment of indicators parameters for industrial environmental sustainability

The industrial activity is inevitably associated with a certain degradation of the environmental quality, because is not possible to guarantee that a manufacturing process can be totally innocuous. The eco-efficiency concept is globally accepted as a philosophy of entreprise management, that encourages the companies to become more competitive, innovative and environmentally responsible by promoting the link between its companies objectives for excellence and its objectives of environmental excellence issues. This link imposes the creation of an organizational methodology where the performance of the company is concordant with the sustainable development. The main propose of this project is to apply the concept of eco-efficiency to the particular case of the metallurgical and metal workshop industries through the development of the particular indicators needed and to produce a manual of procedures for implementation of the accurate solution.

Data analysis applied to the evaluation of a technological nature teaching model as a regional development tool

This paper presents the creation and development of technological schools directly linked to the business community and to higher public education. Establishing themselves as the key interface between the two sectors they make a signigicant contribution by having a greater competitive edge when faced with increasing competition in the tradional markets. The development of new business strategies supported by references of excellence, quality and competitiveness also provides a good link between the estalishment of partnerships aiming at the qualification of education boards at a medium level between the technological school and higher education with a technological foundation. We present a case study as an example depicting the success of Escola Tecnológica de Vale de Cambra.