We present a sparse knowledge gradient (SpKG) algorithm for adaptively selecting the targeted regions within a large RNA molecule to identify which regions are most amenable to interactions with other molecules. Experimentally, such regions can be inferred from fluorescence measurements obtained by binding a complementary probe with fluorescence markers to the targeted regions. We use a biophysical model which shows that the fluorescence ratio under the log scale has a sparse linear relationship with the coefficients describing the accessibility of each nucleotide, since not all sites are accessible (due to the folding of the molecule). The SpKG algorithm uniquely combines the Bayesian ranking and selection problem with the frequentist $\ell_1$ regularized regression approach Lasso. We use this algorithm to identify the sparsity pattern of the linear model as well as sequentially decide the best regions to test before experimental budget is exhausted. Besides, we also develop two other new algorithms: batch SpKG algorithm, which generates more suggestions sequentially to run parallel experiments; and batch SpKG with a procedure which we call length mutagenesis. It dynamically adds in new alternatives, in the form of types of probes, are created by inserting, deleting or mutating nucleotides within existing probes. In simulation, we demonstrate these algorithms on the Group I intron (a mid-size RNA molecule), showing that they efficiently learn the correct sparsity pattern, identify the most accessible region, and outperform several other policies.

In this paper, Bayesian parameter estimation through the consideration of the Maximum A Posteriori (MAP) criterion is revisited under the prism of the Expectation-Maximization (EM) algorithm. By incorporating a sparsity-promoting penalty term in the cost function of the estimation problem through the use of an appropriate prior distribution, we show how the EM algorithm can be used to efficiently solve the corresponding optimization problem. To this end, we rely on variance-mean Gaussian mixtures (VMGM) to describe the prior distribution, while we incorporate many nice features of these mixtures to our estimation problem. The corresponding MAP estimation problem is completely expressed in terms of the EM algorithm, which allows for handling nonlinearities and hidden variables that cannot be easily handled with traditional methods. For comparison purposes, we also develop a Coordinate Descent algorithm for the $\ell_q$-norm penalized problem and present the performance results via simulations.

With different genomes available, unsupervised learning algorithms are essential in learning genome-wide biological insights. Especially, the functional characterization of different genomes is essential for us to understand lives. In this book chapter, we review the state-of-the-art unsupervised learning algorithms for genome informatics from DNA to MicroRNA. DNA (DeoxyriboNucleic Acid) is the basic component of genomes. A significant fraction of DNA regions (transcription factor binding sites) are bound by proteins (transcription factors) to regulate gene expression at different development stages in different tissues. To fully understand genetics, it is necessary of us to apply unsupervised learning algorithms to learn and infer those DNA regions. Here we review several unsupervised learning methods for deciphering the genome-wide patterns of those DNA regions. MicroRNA (miRNA), a class of small endogenous non-coding RNA (RiboNucleic acid) species, regulate gene expression post-transcriptionally by forming imperfect base-pair with the target sites primarily at the 3$'$ untranslated regions of the messenger RNAs. Since the 1993 discovery of the first miRNA \emph{let-7} in worms, a vast amount of studies have been dedicated to functionally characterizing the functional impacts of miRNA in a network context to understand complex diseases such as cancer. Here we review several representative unsupervised learning frameworks on inferring miRNA regulatory network by exploiting the static sequence-based information pertinent to the prior knowledge of miRNA targeting and the dynamic information of miRNA activities implicated by the recently available large data compendia, which interrogate genome-wide expression profiles of miRNAs and/or mRNAs across various cell conditions.

This work introduces algorithms able to exploit contextual information in order to improve maximum-likelihood (ML) parameter estimation in finite mixture models (FMM), demonstrating their benefits and properties in several scenarios. The proposed algorithms are derived in a probabilistic framework with regard to situations where the regular FMM graphs can be extended with context-related variables, respecting the standard expectation-maximization (EM) methodology and, thus, rendering explicit supervision completely redundant. We show that, by direct application of the missing information principle, the compared algorithms' learning behaviour operates between the extremities of supervised and unsupervised learning, proportionally to the information content of contextual assistance. Our simulation results demonstrate the superiority of context-aware FMM training as compared to conventional unsupervised training in terms of estimation precision, standard errors, convergence rates and classification accuracy or regression fitness in various scenarios, while also highlighting important differences among the outlined situations. Finally, the improved classification outcome of contextually enhanced FMMs is showcased in a brain-computer interface application scenario.

We propose an extensive analysis of the behavior of majority votes in binary classification. In particular, we introduce a risk bound for majority votes, called the C-bound, that takes into account the average quality of the voters and their average disagreement. We also propose an extensive PAC-Bayesian analysis that shows how the C-bound can be estimated from various observations contained in the training data. The analysis intends to be self-contained and can be used as introductory material to PAC-Bayesian statistical learning theory. It starts from a general PAC-Bayesian perspective and ends with uncommon PAC-Bayesian bounds. Some of these bounds contain no Kullback-Leibler divergence and others allow kernel functions to be used as voters (via the sample compression setting). Finally, out of the analysis, we propose the MinCq learning algorithm that basically minimizes the C-bound. MinCq reduces to a simple quadratic program. Aside from being theoretically grounded, MinCq achieves state-of-the-art performance, as shown in our extensive empirical comparison with both AdaBoost and the Support Vector Machine.

We present the first fully variational Bayesian inference scheme for continuous Gaussian-process-modulated Poisson processes. Such point processes are used in a variety of domains, including neuroscience, geo-statistics and astronomy, but their use is hindered by the computational cost of existing inference schemes. Our scheme: requires no discretisation of the domain; scales linearly in the number of observed events; and is many orders of magnitude faster than previous sampling based approaches. The resulting algorithm is shown to outperform standard methods on synthetic examples, coal mining disaster data and in the prediction of Malaria incidences in Kenya.

This paper is concerned with a lesser-studied problem in the context of model-based, uncertainty quantification (UQ), that of optimization/design/control under uncertainty. The solution of such problems is hindered not only by the usual difficulties encountered in UQ tasks (e.g. the high computational cost of each forward simulation, the large number of random variables) but also by the need to solve a nonlinear optimization problem involving large numbers of design variables and potentially constraints. We propose a framework that is suitable for a large class of such problems and is based on the idea of recasting them as probabilistic inference tasks. To that end, we propose a Variational Bayesian (VB) formulation and an iterative VB-Expectation-Maximization scheme that is also capable of identifying a low-dimensional set of directions in the design space, along which, the objective exhibits the largest sensitivity. We demonstrate the validity of the proposed approach in the context of two numerical examples involving $\mathcal{O}(10^3)$ random and design variables. In all cases considered the cost of the computations in terms of calls to the forward model was of the order $\mathcal{O}(10^2)$. The accuracy of the approximations provided is assessed by appropriate information-theoretic metrics.

Recently, a framework for application-oriented optimal experiment design has been introduced. In this context, the distance of the estimated system from the true one is measured in terms of a particular end-performance metric. This treatment leads to superior unknown system estimates to classical experiment designs based on usual pointwise functional distances of the estimated system from the true one. The separation of the system estimator from the experiment design is done within this new framework by choosing and fixing the estimation method to either a maximum likelihood (ML) approach or a Bayesian estimator such as the minimum mean square error (MMSE). Since the MMSE estimator delivers a system estimate with lower mean square error (MSE) than the ML estimator for finite-length experiments, it is usually considered the best choice in practice in signal processing and control applications. Within the application-oriented framework a related meaningful question is: Are there end-performance metrics for which the ML estimator outperforms the MMSE when the experiment is finite-length? In this paper, we affirmatively answer this question based on a simple linear Gaussian regression example.

Mixture models are powerful statistical models used in many applications ranging from density estimation to clustering and classification. When dealing with mixture models, there are many issues that the experimenter should be aware of and needs to solve. The MixEst toolbox is a powerful and user-friendly package for MATLAB that implements several state-of-the-art approaches to address these problems. Additionally, MixEst gives the possibility of using manifold optimization for fitting the density model, a feature specific to this toolbox. MixEst simplifies using and integration of mixture models in statistical models and applications. For developing mixture models of new densities, the user just needs to provide a few functions for that statistical distribution and the toolbox takes care of all the issues regarding mixture models. MixEst is available at visionlab.ut.ac.ir/mixest and is fully documented and is licensed under GPL.

Many modern data analysis problems involve inferences from streaming data. However, streaming data is not easily amenable to the standard probabilistic modeling approaches, which assume that we condition on finite data. We develop population variational Bayes, a new approach for using Bayesian modeling to analyze streams of data. It approximates a new type of distribution, the population posterior, which combines the notion of a population distribution of the data with Bayesian inference in a probabilistic model. We study our method with latent Dirichlet allocation and Dirichlet process mixtures on several large-scale data sets.