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Reasoning about the causes behind observations is crucial to the formalization of rationality. While extensive research has been conducted on root cause analysis, most studies have predominantly focused on deterministic settings. In this paper, we investigate causation in more realistic nondeterministic domains, where the agent does not have any control on and may not know the choices that are made by the environment. We build on recent preliminary work on actual causation in the nondeterministic situation calculus to formalize more sophisticated forms of reasoning about actual causes in such domains. We investigate the notions of ``Certainly Causes'' and ``Possibly Causes'' that enable the representation of actual cause for agent actions in these domains. We then show how regression in the situation calculus can be extended to reason about such notions of actual causes.

We develop a general framework for agent abstraction based on the situation calculus and the ConGolog agent programming language. We assume that we have a high-level specification and a low-level specification of the agent, both represented as basic action theories. A refinement mapping specifies how each high-level action is implemented by a low-level ConGolog program and how each high-level fluent can be translated into a low-level formula. We define a notion of sound abstraction between such action theories in terms of the existence of a suitable bisimulation between their respective models. Sound abstractions have many useful properties that ensure that we can reason about the agent's actions (e.g., executability, projection, and planning) at the abstract level, and refine and concretely execute them at the low level. We also characterize the notion of complete abstraction where all actions (including exogenous ones) that the high level thinks can happen can in fact occur at the low level. To facilitate verifying that one has a sound/complete abstraction relative to a mapping, we provide a set of necessary and sufficient conditions. Finally, we identify a set of basic action theory constraints that ensure that for any low-level action sequence, there is a unique high-level action sequence that it refines. This allows us to track/monitor what the low-level agent is doing and describe it in abstract terms (i.e., provide high-level explanations, for instance, to a client or manager)., Comment: 60 pages, 1 figure

Covariate measurement error in regression analysis is an important issue that has been studied extensively under the classical additive and the Berkson error models. Here, we consider cases where covariates are derived from tumor tissue histology, and in particular tissue microarrays. In such settings, biomarkers are evaluated from tissue cores that are subsampled from a larger tissue section so that these biomarkers are only estimates of the true cell densities. The resulting measurement error is non-negligible but is seldom accounted for in the analysis of cancer studies involving tissue microarrays. To adjust for this type of measurement error, we assume that these discrete-valued biomarkers are conditionally Poisson distributed, based on a Poisson process model governing the spatial locations of marker-positive cells. Existing methods for addressing conditional Poisson surrogates, particularly in the absence of internal validation data, are limited. We extend the simulation extrapolation (SIMEX) algorithm to accommodate the conditional Poisson case (POI-SIMEX), where measurement errors are non-Gaussian with heteroscedastic variance. The proposed estimator is shown to be strongly consistent in a linear regression model under the assumption of a conditional Poisson distribution for the observed biomarker. Simulation studies evaluate the performance of POI-SIMEX, comparing it with the naive method and an alternative corrected likelihood approach in linear regression and survival analysis contexts. POI-SIMEX is then applied to a study of high-grade serous cancer, examining the association between survival and the presence of triple-positive biomarker (CD3+CD8+FOXP3+ cells), Comment: 18 pages, 2 figures

We develop a general framework for abstracting the behavior of an agent that operates in a nondeterministic domain, i.e., where the agent does not control the outcome of the nondeterministic actions, based on the nondeterministic situation calculus and the ConGolog programming language. We assume that we have both an abstract and a concrete nondeterministic basic action theory, and a refinement mapping which specifies how abstract actions, decomposed into agent actions and environment reactions, are implemented by concrete ConGolog programs. This new setting supports strategic reasoning and strategy synthesis, by allowing us to quantify separately on agent actions and environment reactions. We show that if the agent has a (strong FOND) plan/strategy to achieve a goal/complete a task at the abstract level, and it can always execute the nondeterministic abstract actions to completion at the concrete level, then there exists a refinement of it that is a (strong FOND) plan/strategy to achieve the refinement of the goal/task at the concrete level., Comment: 20 pages, 2 figures

The vast coastline provides Canada with a flourishing seafood industry including bivalve shellfish production. To sustain a healthy bivalve molluscan shellfish production, the Canadian Shellfish Sanitation Program was established to monitor the health of shellfish harvesting habitats, and fecal coliform bacteria data have been collected at nearly 15,000 marine sample sites across six coastal provinces in Canada since 1979. We applied Functional Principal Component Analysis and subsequent correlation analyses to find annual variation patterns of bacteria levels at sites in each province. The overall magnitude and the seasonality of fecal contamination were modelled by functional principal component one and two, respectively. The amplitude was related to human and warm-blooded animal activities; the seasonality was strongly correlated with river discharge driven by precipitation and snow melt in British Columbia, but such correlation in provinces along the Atlantic coast could not be properly evaluated due to lack of data during winter., Comment: 30 pages, 7 figures, 0 table

Background: Selecting feature genes to predict phenotypes is one of the typical tasks in analyzing genomics data. Though many general-purpose algorithms were developed for prediction, dealing with highly correlated genes in the prediction model is still not well addressed. High correlation among genes introduces technical problems, such as multi-collinearity issues, leading to unreliable prediction models. Furthermore, when a causal gene (whose variants have an actual biological effect on a phenotype) is highly correlated with other genes, most algorithms select the feature gene from the correlated group in a purely data-driven manner. Since the correlation structure among genes could change substantially when condition changes, the prediction model based on not correctly selected feature genes is unreliable. Therefore, we aim to keep the causal biological signal in the prediction process and build a more robust prediction model. Method: We propose a grouping algorithm, which treats highly correlated genes as a group and uses their common pattern to represent the group's biological signal in feature selection. Our novel grouping algorithm can be integrated into existing prediction algorithms to enhance their prediction performance. Our proposed grouping method has two advantages. First, using the gene group's common patterns makes the prediction more robust and reliable under condition change. Second, it reports whole correlated gene groups as discovered biomarkers for prediction tasks, allowing researchers to conduct follow-up studies to identify causal genes within the identified groups. Result: Using real benchmark scRNA-seq datasets with simulated cell phenotypes, we demonstrate our novel method significantly outperforms standard models in both (1) prediction of cell phenotypes and (2) feature gene selection., Comment: 9 pages, 2 figures

Motivation: HIV is difficult to treat because its virus mutates at a high rate and mutated viruses easily develop resistance to existing drugs. If the relationships between mutations and drug resistances can be determined from historical data, patients can be provided personalized treatment according to their own mutation information. The HIV Drug Resistance Database was built to investigate the relationships. Our goal is to build a model using data in this database, which simultaneously predicts the resistance of multiple drugs using mutation information from sequences of viruses for any new patient. Results: We propose two variations of a stacking algorithm which borrow information among multiple prediction tasks to improve multivariate prediction performance. The most attractive feature of our proposed methods is the flexibility with which complex multivariate prediction models can be constructed using any univariate prediction models. Using cross-validation studies, we show that our proposed methods outperform other popular multivariate prediction methods. Availability: An R package will be made available., Comment: 15 pages, 5 figures

Motivation: Recent advances in technology for brain imaging and high-throughput genotyping have motivated studies examining the influence of genetic variation on brain structure. Wang et al. (Bioinformatics, 2012) have developed an approach for the analysis of imaging genomic studies using penalized multi-task regression with regularization based on a novel group $l_{2,1}$-norm penalty which encourages structured sparsity at both the gene level and SNP level. While incorporating a number of useful features, the proposed method only furnishes a point estimate of the regression coefficients; techniques for conducting statistical inference are not provided. A new Bayesian method is proposed here to overcome this limitation. Results: We develop a Bayesian hierarchical modeling formulation where the posterior mode corresponds to the estimator proposed by Wang et al. (Bioinformatics, 2012), and an approach that allows for full posterior inference including the construction of interval estimates for the regression parameters. We show that the proposed hierarchical model can be expressed as a three-level Gaussian scale mixture and this representation facilitates the use of a Gibbs sampling algorithm for posterior simulation. Simulation studies demonstrate that the interval estimates obtained using our approach achieve adequate coverage probabilities that outperform those obtained from the nonparametric bootstrap. Our proposed methodology is applied to the analysis of neuroimaging and genetic data collected as part of the Alzheimer's Disease Neuroimaging Initiative (ADNI), and this analysis of the ADNI cohort demonstrates clearly the value added of incorporating interval estimation beyond only point estimation when relating SNPs to brain imaging endophenotypes.

We investigate the choice of tuning parameters for a Bayesian multi-level group lasso model developed for the joint analysis of neuroimaging and genetic data. The regression model we consider relates multivariate phenotypes consisting of brain summary measures (volumetric and cortical thickness values) to single nucleotide polymorphism (SNPs) data and imposes penalization at two nested levels, the first corresponding to genes and the second corresponding to SNPs. Associated with each level in the penalty is a tuning parameter which corresponds to a hyperparameter in the hierarchical Bayesian formulation. Following previous work on Bayesian lassos we consider the estimation of tuning parameters through either hierarchical Bayes based on hyperpriors and Gibbs sampling or through empirical Bayes based on maximizing the marginal likelihood using a Monte Carlo EM algorithm. For the specific model under consideration we find that these approaches can lead to severe overshrinkage of the regression parameter estimates in the high-dimensional setting or when the genetic effects are weak. We demonstrate these problems through simulation examples and study an approximation to the marginal likelihood which sheds light on the cause of this problem. We then suggest an alternative approach based on the widely applicable information criterion (WAIC), an asymptotic approximation to leave-one-out cross-validation that can be computed conveniently within an MCMC framework., Comment: 11 pages, 3 figures

In this paper, we investigate bounded action theories in the situation calculus. A bounded action theory is one which entails that, in every situation, the number of object tuples in the extension of fluents is bounded by a given constant, although such extensions are in general different across the infinitely many situations. We argue that such theories are common in applications, either because facts do not persist indefinitely or because the agent eventually forgets some facts, as new ones are learnt. We discuss various classes of bounded action theories. Then we show that verification of a powerful first-order variant of the mu-calculus is decidable for such theories. Notably, this variant supports a controlled form of quantification across situations. We also show that through verification, we can actually check whether an arbitrary action theory maintains boundedness., Comment: 51 pages