The emergence and development of cancer is a consequence of the accumulation over time of genomic mutations involving a specific set of genes, which provides the cancer clones with a functional selective advantage. In this work, we model the order of accumulation of such mutations during the progression, which eventually leads to the disease, by means of probabilistic graphic models, i.e., Bayesian Networks (BNs). We investigate how to perform the task of learning the structure of such BNs, according to experimental evidence, adopting a global optimization meta-heuristics. In particular, in this work we rely on Genetic Algorithms, and to strongly reduce the execution time of the inference -- which can also involve multiple repetitions to collect statistically significant assessments of the data -- we distribute the calculations using both multi-threading and a multi-node architecture. The results show that our approach is characterized by good accuracy and specificity; we also demonstrate its feasibility, thanks to a 84x reduction of the overall execution time with respect to a traditional sequential implementation.

To obtain uncertainty estimates with real-world Bayesian deep learning models, practical inference approximations are needed. Dropout variational inference (VI) for example has been used for machine vision and medical applications, but VI can severely underestimates model uncertainty. Alpha-divergences are alternative divergences to VI's KL objective, which are able to avoid VI's uncertainty underestimation. But these are hard to use in practice: existing techniques can only use Gaussian approximating distributions, and require existing models to be changed radically, thus are of limited use for practitioners. We propose a re-parametrisation of the alpha-divergence objectives, deriving a simple inference technique which, together with dropout, can be easily implemented with existing models by simply changing the loss of the model. We demonstrate improved uncertainty estimates and accuracy compared to VI in dropout networks. We study our model's epistemic uncertainty far away from the data using adversarial images, showing that these can be distinguished from non-adversarial images by examining our model's uncertainty.

Proportional, Integral and Derivative (PID) control structures are still the main control tool being used in industrial applications, in particular in the process industry [1], but also in automotive applications [2] and in low-level control in robotics [3]. The large share of PID controlled applications is mainly due to the past record of success, the wide availability, and the simplicity in use of this technique. In practice, control design is still often achieved by tedious manual tuning or by heuristic PID tuning rules [4]. More advanced tuning concepts are most frequently developed for Single-Input-Single-Output (SISO) systems [5], [6]. For Multi-Input-Multi-Output (MIMO) systems, popular tuning methods, such as biggest log-modulus and the dominant pole placement tuning method [7], strive to tune each control loop individually, followed by a collective de-tuning to stabilize the multi-loop system. These tuning methods, however, rely on linear process models and require stable processes. For general PID control structures where multiple controllers act on each input, controller design is usually conducted by decoupling the process, subsequently allowing the design of individual SISO PIDs. One example are online adjusted precompensators, which decouple the process transfer function matrix [8].

We present a Bayesian model selection approach to estimate the intrinsic dimensionality of a high-dimensional dataset. To this end, we introduce a novel formulation of the probabilisitic principal component analysis model based on a normal-gamma prior distribution. In this context, we exhibit a closed-form expression of the marginal likelihood which allows to infer an optimal number of components. We also propose a heuristic based on the expected shape of the marginal likelihood curve in order to choose the hyperparameters. In non-asymptotic frameworks, we show on simulated data that this exact dimensionality selection approach is competitive with both Bayesian and frequentist state-of-the-art methods.

This paper studies the nonparametric modal regression problem systematically from a statistical learning view. Originally motivated by pursuing a theoretical understanding of the maximum correntropy criterion based regression (MCCR), our study reveals that MCCR with a tending-to-zero scale parameter is essentially modal regression. We show that nonparametric modal regression problem can be approached via the classical empirical risk minimization. Some efforts are then made to develop a framework for analyzing and implementing modal regression. For instance, the modal regression function is described, the modal regression risk is defined explicitly and its \textit{Bayes} rule is characterized; for the sake of computational tractability, the surrogate modal regression risk, which is termed as the generalization risk in our study, is introduced. On the theoretical side, the excess modal regression risk, the excess generalization risk, the function estimation error, and the relations among the above three quantities are studied rigorously. It turns out that under mild conditions, function estimation consistency and convergence may be pursued in modal regression as in vanilla regression protocols, such as mean regression, median regression, and quantile regression. However, it outperforms these regression models in terms of robustness as shown in our study from a re-descending M-estimation view. This coincides with and in return explains the merits of MCCR on robustness. On the practical side, the implementation issues of modal regression including the computational algorithm and the tuning parameters selection are discussed. Numerical assessments on modal regression are also conducted to verify our findings empirically.

Noname manuscript No. (will be inserted by the editor) Abstract Several diseases related to cell proliferation are characterized by the accumulation of somatic DNA changes, with respect to wildtype conditions. Cancer and HIV are two common examples of such diseases, where the mutational load in the cancerous/viral population increases over time. In these cases, selective pressures are often observed along with competition, cooperation and parasitism among distinct cellular clones. Recently, we presented a mathematical framework to model these phenomena, based on a combination of Bayesian inference and Suppes' theory of probabilistic causation, depicted in graphical structures dubbed Suppes-Bayes Causal Networks ( SBCNs). SBCNs are generative probabilistic graphical models that recapitulate the potential ordering of accumulation of such DNA changes during the progression of the disease. Such models can be inferred from data by exploiting likelihood-based model-selection strategies with regularization. In this paper we discuss the theoretical foundations of our approach and we investigate in depth the influence on the model-selection task of: (i) the poset based on Suppes' theory and (ii) different regularization strategies. Furthermore, we provide an example of application of our framework to HIV genetic data high-Daniele Ramazzotti Department of Pathology, Stanford University, Stanford, CA 94305, USA Email: daniele.ramazzotti@stanford.edu Alex Graudenzi Department of Informatics, Systems and Communication, University of Milan-Bicocca, Milan, Italy Giulio Caravagna School of Informatics, University of Edinburgh, Edinburgh, UK Marco Antoniotti Department of Informatics, Systems and Communication, University of Milan-Bicocca, Milan, Italy Keywords Cumulative Phenomena· Bayesian Graphical Models· Probabilistic Causality 1 Introduction A number of diseases are characterized by the accumulation of genomic lesions in the DNA of a population of cells. Such lesions are often classified as mutations, if they involve one or few nucleotides, or chromosomal alterations, if they involve wider regions of a chromosome.

Discrimination discovery from data is an important task aiming at identifying patterns of illegal and unethical discriminatory activities against protected-by-law groups, e.g., ethnic minorities. While any legally-valid proof of discrimination requires evidence of causality, the state-of-the-art methods are essentially correlation-based, albeit, as it is well known, correlation does not imply causation. In this paper we take a principled causal approach to the data mining problem of discrimination detection in databases. Following Suppes' probabilistic causation theory, we define a method to extract, from a dataset of historical decision records, the causal structures existing among the attributes in the data. The result is a type of constrained Bayesian network, which we dub Suppes-Bayes Causal Network (SBCN). Next, we develop a toolkit of methods based on random walks on top of the SBCN, addressing different anti-discrimination legal concepts, such as direct and indirect discrimination, group and individual discrimination, genuine requirement, and favoritism. Our experiments on real-world datasets confirm the inferential power of our approach in all these different tasks.

We propose Edward, a Turing-complete probabilistic programming language. Edward defines two compositional representations---random variables and inference. By treating inference as a first class citizen, on a par with modeling, we show that probabilistic programming can be as flexible and computationally efficient as traditional deep learning. For flexibility, Edward makes it easy to fit the same model using a variety of composable inference methods, ranging from point estimation to variational inference to MCMC. In addition, Edward can reuse the modeling representation as part of inference, facilitating the design of rich variational models and generative adversarial networks. For efficiency, Edward is integrated into TensorFlow, providing significant speedups over existing probabilistic systems. For example, we show on a benchmark logistic regression task that Edward is at least 35x faster than Stan and 6x faster than PyMC3. Further, Edward incurs no runtime overhead: it is as fast as handwritten TensorFlow.

Record linkage involves merging records in large, noisy databases to remove duplicate entities. It has become an important area because of its widespread occurrence in bibliometrics, public health, official statistics production, political science, and beyond. Traditional linkage methods directly linking records to one another are computationally infeasible as the number of records grows. As a result, it is increasingly common for researchers to treat record linkage as a clustering task, in which each latent entity is associated with one or more noisy database records. We critically assess performance bounds using the Kullback-Leibler (KL) divergence under a Bayesian record linkage framework, making connections to Kolchin partition models. We provide an upper bound using the KL divergence and a lower bound on the minimum probability of misclassifying a latent entity. We give insights for when our bounds hold using simulated data and provide practical user guidance.

We consider the problem of learning a causal graph over a set of variables with interventions. We study the cost-optimal causal graph learning problem: For a given skeleton (undirected version of the causal graph), design the set of interventions with minimum total cost, that can uniquely identify any causal graph with the given skeleton. We show that this problem is solvable in polynomial time. Later, we consider the case when the number of interventions is limited. For this case, we provide polynomial time algorithms when the skeleton is a tree or a clique tree. For a general chordal skeleton, we develop an efficient greedy algorithm, which can be improved when the causal graph skeleton is an interval graph.