We propose a nonparametric Bayesian factor regression model that accounts for uncertainty in the number of factors, and the relationship between factors. To accomplish this, we propose a sparse variant of the Indian Buffet Process and couple this with a hierarchical model over factors, based on Kingman's coalescent. We apply this model to two problems (factor analysis and factor regression) in gene-expression data analysis.
A number of probabilistic approaches have been proposed in the past for the problem of gene-regulatory network reconstruction @cite_10 @cite_13 @cite_4 @cite_3 . Some take into account the information on the prior network topology @cite_10 , which is not always available. Most assume the number of factors is known. To get around this, one can perform model selection via Reversible Jump MCMC @cite_0 or evolutionary stochastic model search @cite_12 . Unfortunately, these methods are often difficult to design and may take quite long to converge. Moreover, they are difficult to integrate with other forms of prior knowledge (eg., factor hierarchies). A somewhat similar approach to ours is the infinite independent component analysis (iICA) model of @cite_8 which treats factor analysis as a special case of ICA. However, their model is limited to factor analysis and does not take into account feature selection, factor hierarchy and factor regression. As a generalization to the standard ICA model, @cite_11 proposed a model in which the components can be related via a tree-structured graphical model. It, however, assumes a fixed number of components.
@cite_4 @cite_8 @cite_10 @cite_3 @cite_0 @cite_13 @cite_12 @cite_11
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We consider the problem of discovering gene regulatory networks from time-series microarray data. Recently, graphical Granger modeling has gained considerable attention as a promising direction for addressing this problem. These methods apply graphical modeling methods on time-series data and invoke the notion of ‘Granger causality’ to make assertions on causality through inference on time-lagged effects. Existing algorithms, however, have neglected an important aspect of the problem—the group structure among the lagged temporal variables naturally imposed by the time series they belong to. Specifically, existing methods in computational biology share this shortcoming, as well as additional computational limitations, prohibiting their effective applications to the large datasets including a large number of genes and many data points. In the present article, we propose a novel methodology which we term ‘grouped graphical Granger modeling method’, which overcomes the limitations mentioned above by applying a regression method suited for high-dimensional and large data, and by leveraging the group structure among the lagged temporal variables according to the time series they belong to. We demonstrate the effectiveness of the proposed methodology on both simulated and actual gene expression data, specifically the human cancer cell (HeLa S3) cycle data. The simulation results show that the proposed methodology generally exhibits higher accuracy in recovering the underlying causal structure. Those on the gene expression data demonstrate that it leads to improved accuracy with respect to prediction of known links, and also uncovers additional causal relationships uncaptured by earlier works. Contact: aclozano@us.ibm.com The identification of probabilistic cellular automata (PCA) is studied using a new two stage neighborhood detection algorithm. It is shown that a binary probabilistic cellular automaton (BPCA) can be described by an integer-parameterized polynomial corrupted by noise. Searching for the correct neighborhood of a BPCA is then equivalent to selecting the correct terms which constitute the polynomial model of the BPCA, from a large initial term set. It is proved that the contribution values for the correct terms can be calculated independently of the contribution values for the noise terms. This allows the neighborhood detection technique developed for deterministic rules in to be applied with a larger cutoff value to discard the majority of spurious terms and to produce an initial presearch for the BPCA neighborhood. A multiobjective genetic algorithm (GA) search with integer constraints is then evolved to refine the reduced neighborhood and to identify the polynomial rule which is equivalent to the probabilistic rule with the largest probability. A probability table representing the BPCA can then be determined based on the identified neighborhood and the deterministic rule. The new algorithm is tested over a large set of one-dimensional (1D), two-dimensional (2D), and three-dimensional (3D) BPCA rules. Simulation results demonstrate the efficiency of the new method. Objective Build probabilistic topic model representations of hospital admissions processes and compare the ability of such models to predict clinical order patterns as compared to preconstructed order sets. @PARASPLIT Materials and Methods The authors evaluated the first 24 hours of structured electronic health record data for > 10 K inpatients. Drawing an analogy between structured items (e.g., clinical orders) to words in a text document, the authors performed latent Dirichlet allocation probabilistic topic modeling. These topic models use initial clinical information to predict clinical orders for a separate validation set of > 4 K patients. The authors evaluated these topic model-based predictions vs existing human-authored order sets by area under the receiver operating characteristic curve, precision, and recall for subsequent clinical orders. @PARASPLIT Results Existing order sets predict clinical orders used within 24 hours with area under the receiver operating characteristic curve 0.81, precision 16 , and recall 35 . This can be improved to 0.90, 24 , and 47 ( P < 10−20) by using probabilistic topic models to summarize clinical data into up to 32 topics. Many of these latent topics yield natural clinical interpretations (e.g., “critical care,” “pneumonia,” “neurologic evaluation”). @PARASPLIT Discussion Existing order sets tend to provide nonspecific, process-oriented aid, with usability limitations impairing more precise, patient-focused support. Algorithmic summarization has the potential to breach this usability barrier by automatically inferring patient context, but with potential tradeoffs in interpretability. @PARASPLIT Conclusion Probabilistic topic modeling provides an automated approach to detect thematic trends in patient care and generate decision support content. A potential use case finds related clinical orders for decision support. Motivation: Approaches for testing sets of variants, such as a set of rare or common variants within a gene or pathway, for association with complex traits are important. In particular, set tests allow for aggregation of weak signal within a set, can capture interplay among variants and reduce the burden of multiple hypothesis testing. Until now, these approaches did not address confounding by family relatedness and population structure, a problem that is becoming more important as larger datasets are used to increase power. Results: We introduce a new approach for set tests that handles confounders. Our model is based on the linear mixed model and uses two random effects—one to capture the set association signal and one to capture confounders. We also introduce a computational speedup for two random-effects models that makes this approach feasible even for extremely large cohorts. Using this model with both the likelihood ratio test and score test, we find that the former yields more power while controlling type I error. Application of our approach to richly structured Genetic Analysis Workshop 14 data demonstrates that our method successfully corrects for population structure and family relatedness, whereas application of our method to a 15 000 individual Crohn’s disease case–control cohort demonstrates that it additionally recovers genes not recoverable by univariate analysis. Availability: A Python-based library implementing our approach is available at http: mscompbio.codeplex.com. Contact:jennl@microsoft.com or lippert@microsoft.com or heckerma@microsoft.com Supplementary information:Supplementary data are available at Bioinformatics online. A novel regularizer of the PARAFAC decomposition factors capturing the tensor's rank is proposed in this paper, as the key enabler for completion of three-way data arrays with missing entries. Set in a Bayesian framework, the tensor completion method incorporates prior information to enhance its smoothing and prediction capabilities. This probabilistic approach can naturally accommodate general models for the data distribution, lending itself to various fitting criteria that yield optimum estimates in the maximum-a-posteriori sense. In particular, two algorithms are devised for Gaussian- and Poisson-distributed data, that minimize the rank-regularized least-squares error and Kullback-Leibler divergence, respectively. The proposed technique is able to recover the “ground-truth” tensor rank when tested on synthetic data, and to complete brain imaging and yeast gene expression datasets with 50 and 15 of missing entries respectively, resulting in recovery errors at -11 dB and -15 dB. Consider the random graph models G(n, #edges = M) and G(n, Prob(edge) = p) with M = M(n) = (1 + )n-1 3)n 2 and p = p(n) = (1 +An-1 3) n . For 1 > -1 define an i-component of a random graph as a component which has exactly I more edges than vertices. Call an i-component with I > 1 a complex component. For both models, we show that when A is constant, the expected number of complex components is bounded, almost surely (a.s.) each of these components (if any exist) has size of order n2 3, and the maximum value of I is bounded in probability. We prove that a.s. the largest suspended tree in each complex component has size of order n2 3, and deletion of all suspended trees results in a "smoothed" graph of size of order n 3, with the maximum vertex degree 3. The total number of branching vertices, i.e., of degree 3, is bounded in probability. Thus, each complex component is almost surely topologically equivalent to a 3-regular multigraph of a uniformly bounded size. Lengths of the shortest cycle and of the shortest path between two branching vertices of a smoothed graph are each of order n 3. We find a relatively simple integral formula for the limit distribution of the numbers of complex components, which implies, in particular, that all values of the "complexity spectrum" have positive limiting probabilities. We also answer questions raised by Erdos and Renyi back in 1960. It is proven that there exists p(A), the limiting planarity probability, with 0 < p(A) < 1, p(-oo) = 1, p(oo) = 0. In particular, G(n, M) (G(n, p), resp.) is almost surely nonplanar iff (M n 2)n-213 -* 00 ((np I)n-1 3) -+ oo, resp.). In many multivariate domains, we are interested in analyzing the dependency structure of the underlying distribution, e.g., whether two variables are in direct interaction. We can represent dependency structures using Bayesian network models. To analyze a given data set, Bayesian model selection attempts to find the most likely (MAP) model, and uses its structure to answer these questions. However, when the amount of available data is modest, there might be many models that have non-negligible posterior. Thus, we want compute the Bayesian posterior of a feature, i.e., the total posterior probability of all models that contain it. In this paper, we propose a new approach for this task. We first show how to efficiently compute a sum over the exponential number of networks that are consistent with a fixed order over network variables. This allows us to compute, for a given order, both the marginal probability of the data and the posterior of a feature. We then use this result as the basis for an algorithm that approximates the Bayesian posterior of a feature. Our approach uses a Markov Chain Monte Carlo (MCMC) method, but over orders rather than over network structures. The space of orders is smaller and more regular than the space of structures, and has much a smoother posterior “landscape”. We present empirical results on synthetic and real-life datasets that compare our approach to full model averaging (when possible), to MCMC over network structures, and to a non-Bayesian bootstrap approach. A recent and effective approach to probabilistic inference calls for reducing the problem to one of weighted model counting (WMC) on a propositional knowledge base. Specifically, the approach calls for encoding the probabilistic model, typically a Bayesian network, as a propositional knowledge base in conjunctive normal form (CNF) with weights associated to each model according to the network parameters. Given this CNF, computing the probability of some evidence becomes a matter of summing the weights of all CNF models consistent with the evidence. A number of variations on this approach have appeared in the literature recently, that vary across three orthogonal dimensions. The first dimension concerns the specific encoding used to convert a Bayesian network into a CNF. The second dimensions relates to whether weighted model counting is performed using a search algorithm on the CNF, or by compiling the CNF into a structure that renders WMC a polytime operation in the size of the compiled structure. The third dimension deals with the specific properties of network parameters (local structure) which are captured in the CNF encoding. In this paper, we discuss recent work in this area across the above three dimensions, and demonstrate empirically its practical importance in significantly expanding the reach of exact probabilistic inference. We restrict our discussion to exact inference and model counting, even though other proposals have been extended for approximate inference and approximate model counting.