We present a new package in R implementing Bayesian additive regression trees (BART). The package introduces many new features for data analysis using BART such as variable selection, interaction detection, model diagnostic plots, incorporation of missing data and the ability to save trees for future prediction. It is significantly faster than the current R implementation, parallelized, and capable of handling both large sample sizes and high-dimensional data.

According to Cobanoglu et al and Murphy, it is now widely acknowledged that the single target paradigm (one protein or target, one disease, one drug) that has been the dominant premise in drug development in the recent past is untenable. More often than not, a drug-like compound (ligand) can be promiscuous - that is, it can interact with more than one target protein. In recent years, in in silico target prediction methods the promiscuity issue has been approached computationally in different ways. In this study we confine attention to the so-called ligand-based target prediction machine learning approaches, commonly referred to as target-fishing. With a few exceptions, the target-fishing approaches that are currently ubiquitous in cheminformatics literature can be essentially viewed as single-label multi-classification schemes; these approaches inherently bank on the single target paradigm assumption that a ligand can home in on one specific target. In order to address the ligand promiscuity issue, one might be able to cast target-fishing as a multi-label multi-class classification problem. For illustrative and comparison purposes, single-label and multi-label Naive Bayes classification models (denoted here by SMM and MMM, respectively) for target-fishing were implemented. The models were constructed and tested on 65,587 compounds and 308 targets retrieved from the ChEMBL17 database. SMM and MMM performed differently: for 16,344 test compounds, the MMM model returned recall and precision values of 0.8058 and 0.6622, respectively; the corresponding recall and precision values yielded by the SMM model were 0.7805 and 0.7596, respectively. However, at a significance level of 0.05 and one degree of freedom McNemar test performed on the target prediction results returned by SMM and MMM for the 16,344 test ligands gave a chi-squared value of 15.656, in favour of the MMM approach.

Recently fair division theory has emerged as a promising approach for allocation of multiple computational resources among agents. While in reality agents are not all present in the system simultaneously, previous work has studied static settings where all relevant information is known upfront. Our goal is to better understand the dynamic setting. On the conceptual level, we develop a dynamic model of fair division, and propose desirable axiomatic properties for dynamic resource allocation mechanisms. On the technical level, we construct two novel mechanisms that provably satisfy some of these properties, and analyze their performance using real data. We believe that our work informs the design of superior multiagent systems, and at the same time expands the scope of fair division theory by initiating the study of dynamic and fair resource allocation mechanisms.

The Workflow Satisfiability Problem (WSP) is a problem of practical interest that arises whenever tasks need to be performed by authorized users, subject to constraints defined by business rules. We are required to decide whether there exists a plan - an assignment of tasks to authorized users - such that all constraints are satisfied. It is natural to see the WSP as a subclass of the Constraint Satisfaction Problem (CSP) in which the variables are tasks and the domain is the set of users. What makes the WSP distinctive is that the number of tasks is usually very small compared to the number of users, so it is appropriate to ask for which constraint languages the WSP is fixed-parameter tractable (FPT), parameterized by the number of tasks. This novel approach to the WSP, using techniques from CSP, has enabled us to design a generic algorithm which is FPT for several families of workflow constraints considered in the literature. Furthermore, we prove that the union of FPT languages remains FPT if they satisfy a simple compatibility condition. Lastly, we identify a new FPT constraint language, user-independent constraints, that includes many of the constraints of interest in business processing systems. We demonstrate that our generic algorithm has provably optimal running time O*(2^(klog k)), for this language, where k is the number of tasks.

In this thesis, we propose several modelling strategies to tackle evolving data in different contexts. In the framework of static clustering, we start by introducing a soft kernel spectral clustering (SKSC) algorithm, which can better deal with overlapping clusters with respect to kernel spectral clustering (KSC) and provides more interpretable outcomes. Afterwards, a whole strategy based upon KSC for community detection of static networks is proposed, where the extraction of a high quality training sub-graph, the choice of the kernel function, the model selection and the applicability to large-scale data are key aspects. This paves the way for the development of a novel clustering algorithm for the analysis of evolving networks called kernel spectral clustering with memory effect (MKSC), where the temporal smoothness between clustering results in successive time steps is incorporated at the level of the primal optimization problem, by properly modifying the KSC formulation. Later on, an application of KSC to fault detection of an industrial machine is presented. Here, a smart pre-processing of the data by means of a proper windowing operation is necessary to catch the ongoing degradation process affecting the machine. In this way, in a genuinely unsupervised manner, it is possible to raise an early warning when necessary, in an online fashion. Finally, we propose a new algorithm called incremental kernel spectral clustering (IKSC) for online learning of non-stationary data. This ambitious challenge is faced by taking advantage of the out-of-sample property of kernel spectral clustering (KSC) to adapt the initial model, in order to tackle merging, splitting or drifting of clusters across time. Real-world applications considered in this thesis include image segmentation, time-series clustering, community detection of static and evolving networks.

Modeling dynamical systems with ordinary differential equations implies a mechanistic view of the process underlying the dynamics. However in many cases, this knowledge is not available. To overcome this issue, we introduce a general framework for nonparametric ODE models using penalized regression in Reproducing Kernel Hilbert Spaces (RKHS) based on operator-valued kernels. Moreover, we extend the scope of gradient matching approaches to nonparametric ODE. A smooth estimate of the solution ODE is built to provide an approximation of the derivative of the ODE solution which is in turn used to learn the nonparametric ODE model. This approach benefits from the flexibility of penalized regression in RKHS allowing for ridge or (structured) sparse regression as well. Very good results are shown on 3 different ODE systems.

In this work, we propose a simple yet effective solution to the problem of connectome inference in calcium imaging data. The proposed algorithm consists of two steps. First, processing the raw signals to detect neural peak activities. Second, inferring the degree of association between neurons from partial correlation statistics. This paper summarises the methodology that led us to win the Connectomics Challenge, proposes a simplified version of our method, and finally compares our results with respect to other inference methods.

Bell's Theorem shows that quantum mechanical correlations can violate the constraints that the causal structure of certain experiments impose on any classical explanation. It is thus natural to ask to which degree the causal assumptions -- e.g. locality or measurement independence -- have to be relaxed in order to allow for a classical description of such experiments. Here, we develop a conceptual and computational framework for treating this problem. We employ the language of Bayesian networks to systematically construct alternative causal structures and bound the degree of relaxation using quantitative measures that originate from the mathematical theory of causality. The main technical insight is that the resulting problems can often be expressed as computationally tractable linear programs. We demonstrate the versatility of the framework by applying it to a variety of scenarios, ranging from relaxations of the measurement independence, locality and bilocality assumptions, to a novel causal interpretation of CHSH inequality violations.

The problem of optimal switching between nonlinear autonomous subsystems is investigated in this study where the objective is not only bringing the states to close to the desired point, but also adjusting the switching pattern, in the sense of penalizing switching occurrences and assigning different preferences to utilization of different modes. The mode sequence is unspecified and a switching cost term is used in the cost function for penalizing each switching. It is shown that once a switching cost is incorporated, the optimal cost-to-go function depends on the already active subsystem, i.e., the subsystem which was engaged in the previous time step. Afterwards, an approximate dynamic programming based method is developed which provides an approximation of the optimal solution to the problem in a feedback form and for different initial conditions. Finally, the performance of the method is analyzed through numerical examples.

Semi-supervised learning is an important and active topic of research in pattern recognition. For classification using linear discriminant analysis specifically, several semi-supervised variants have been proposed. Using any one of these methods is not guaranteed to outperform the supervised classifier which does not take the additional unlabeled data into account. In this work we compare traditional Expectation Maximization type approaches for semi-supervised linear discriminant analysis with approaches based on intrinsic constraints and propose a new principled approach for semi-supervised linear discriminant analysis, using so-called implicit constraints. We explore the relationships between these methods and consider the question if and in what sense we can expect improvement in performance over the supervised procedure. The constraint based approaches are more robust to misspecification of the model, and may outperform alternatives that make more assumptions on the data, in terms of the log-likelihood of unseen objects.