Conserved histidine of metal transporter AtNRAMP1 is crucial for optimal plant growth under manganese deficiency at chilling temperatures

Manganese (Mn) is an essential nutrient required for plant growth, in particular in the process of photosynthesis. Plant performance is influenced by various environmental stresses including contrasting temperatures, light or nutrient deficiencies. The molecular responses of plants exposed to such stress factors in combination are largely unknown. 

Screening of 108 Arabidopsis thaliana (Arabidopsis) accessions for reduced photosynthetic performance at chilling temperatures was performed and one accession (Hog) was isolated. Using genetic and molecular approaches, the molecular basis of this particular response to temperature (GxE interaction) was identified. 

Hog showed an induction of a severe leaf chlorosis and impaired growth after transfer to lower temperatures. We demonstrated that this response was dependent on the nutrient content of the soil. Genetic mapping and complementation identified NRAMP1 as the causal gene. Chlorotic phenotype was associated with a histidine to tyrosine (H239Y) substitution in the allele of Hog NRAMP1. This led to lethality when Hog seedlings were directly grown at 4 degrees C. 

Chemical complementation and hydroponic culture experiments showed that Mn deficiency was the major cause of this GxE interaction. For the first time, the NRAMP-specific highly conserved histidine was shown to be crucial for plant performance.

Patient survival following arteriovenous fistula formation

PURPOSE: Efforts to promote arteriovenous fistulas (AVFs) have been successful in increasing the prevalence of AVF use as the primary vascular access for haemodialysis (HD). Sustained preference for AVF use may not be the most appropriate vascular access choice for all patient groups. Arteriovenous grafts (AVGs) offer advantages of earlier use and lower primary failure rates compared to AVFs so may be preferable for patients where short-term vascular access is needed. This study was designed to assess comparative mortality in different age groups following AVF formation.

METHODS: A prospective cohort of patients having AVF creation was recruited. Patients were subdivided into three age groups: Group A: lt;50 years; Group B: 50-74 years and Group C: ≥75 years. Survival curves and Cox regression analysis were performed on each of these groups.

RESULTS: One hundred and thirty-four patients (n = 134) were recruited into the study. The prevalence of diabetes increased significantly with age. As expected, mortality was higher in older age groups (log rank (Mantel-Cox) 19.227; p = 0.0001). Mortality rates at 1 year were 0% in group A, 12.5% in group B and 29.1% in group C. Medium-term mortality at 4 years was 7.9% in group A, 39.1% in group B and 54.8% in group C.

CONCLUSIONS: We found a significantly higher mortality rate in patients ≥75 years in comparison to those lt;75 years. The choice of vascular access modality should be tailored to the individual with particular reference to the patient's expected survival.

Global Sensitivity Analysis for MAP Inference in Graphical Models

We study the sensitivity of a MAP configuration of a discrete probabilistic graphical model with respect to perturbations of its parameters. These perturbations are global, in the sense that simultaneous perturbations of all the parameters (or any chosen subset of them) are allowed. Our main contribution is an exact algorithm that can check whether the MAP configuration is robust with respect to given perturbations. Its complexity is essentially the same as that of obtaining the MAP configuration itself, so it can be promptly used with minimal effort. We use our algorithm to identify the largest global perturbation that does not induce a change in the MAP configuration, and we successfully apply this robustness measure in two practical scenarios: the prediction of facial action units with posed images and the classification of multiple real public data sets. A strong correlation between the proposed robustness measure and accuracy is verified in both scenarios.

Min-BDeu and Max-BDeu Scores for Learning Bayesian Networks

This work presents two new score functions based on the Bayesian Dirichlet equivalent uniform (BDeu) score for learning Bayesian network structures. They consider the sensitivity of BDeu to varying parameters of the Dirichlet prior. The scores take on the most adversary and the most beneficial priors among those within a contamination set around the symmetric one. We build these scores in such way that they are decomposable and can be computed efficiently. Because of that, they can be integrated into any state-of-the-art structure learning method that explores the space of directed acyclic graphs and allows decomposable scores. Empirical results suggest that our scores outperform the standard BDeu score in terms of the likelihood of unseen data and in terms of edge discovery with respect to the true network, at least when the training sample size is small. We discuss the relation between these new scores and the accuracy of inferred models. Moreover, our new criteria can be used to identify the amount of data after which learning is saturated, that is, additional data are of little help to improve the resulting model.

Extended Tree Augmented Naive Classifier

This work proposes an extended version of the well-known tree-augmented naive Bayes (TAN) classifier where the structure learning step is performed without requiring features to be connected to the class. Based on a modification of Edmonds’ algorithm, our structure learning procedure explores a superset of the structures that are considered by TAN, yet achieves global optimality of the learning score function in a very efficient way (quadratic in the number of features, the same complexity as learning TANs). A range of experiments show that we obtain models with better accuracy than TAN and comparable to the accuracy of the state-of-the-art classifier averaged one-dependence estimator.

Advances in Learning Bayesian Networks of Bounded Treewidth

This work presents novel algorithms for learning Bayesian networks of bounded treewidth. Both exact and approximate methods are developed. The exact method combines mixed integer linear programming formulations for structure learning and treewidth computation. The approximate method consists in sampling k-trees (maximal graphs of treewidth k), and subsequently selecting, exactly or approximately, the best structure whose moral graph is a subgraph of that k-tree. The approaches are empirically compared to each other and to state-of-the-art methods on a collection of public data sets with up to 100 variables.

Probabilistic Inference in Credal Networks: New Complexity Results

Credal networks are graph-based statistical models whose parameters take values in a set, instead of being sharply specified as in traditional statistical models (e.g., Bayesian networks). The computational complexity of inferences on such models depends on the irrelevance/independence concept adopted. In this paper, we study inferential complexity under the concepts of epistemic irrelevance and strong independence. We show that inferences under strong independence are NP-hard even in trees with binary variables except for a single ternary one. We prove that under epistemic irrelevance the polynomial-time complexity of inferences in credal trees is not likely to extend to more general models (e.g., singly connected topologies). These results clearly distinguish networks that admit efficient inferences and those where inferences are most likely hard, and settle several open questions regarding their computational complexity. We show that these results remain valid even if we disallow the use of zero probabilities. We also show that the computation of bounds on the probability of the future state in a hidden Markov model is the same whether we assume epistemic irrelevance or strong independence, and we prove an analogous result for inference in Naive Bayes structures. These inferential equivalences are important for practitioners, as hidden Markov models and Naive Bayes networks are used in real applications of imprecise probability.

Discovering subgroups of patients from DNA copy number data using NMF on compacted matrices

In the study of complex genetic diseases, the identification of subgroups of patients sharing similar genetic characteristics represents a challenging task, for example, to improve treatment decision. One type of genetic lesion, frequently investigated in such disorders, is the change of the DNA copy number (CN) at specific genomic traits. Non-negative Matrix Factorization (NMF) is a standard technique to reduce the dimensionality of a data set and to cluster data samples, while keeping its most relevant information in meaningful components. Thus, it can be used to discover subgroups of patients from CN profiles. It is however computationally impractical for very high dimensional data, such as CN microarray data. Deciding the most suitable number of subgroups is also a challenging problem. The aim of this work is to derive a procedure to compact high dimensional data, in order to improve NMF applicability without compromising the quality of the clustering. This is particularly important for analyzing high-resolution microarray data. Many commonly used quality measures, as well as our own measures, are employed to decide the number of subgroups and to assess the quality of the results. Our measures are based on the idea of identifying robust subgroups, inspired by biologically/clinically relevance instead of simply aiming at well-separated clusters. We evaluate our procedure using four real independent data sets. In these data sets, our method was able to find accurate subgroups with individual molecular and clinical features and outperformed the standard NMF in terms of accuracy in the factorization fitness function. Hence, it can be useful for the discovery of subgroups of patients with similar CN profiles in the study of heterogeneous diseases.

Kuznetsov independence for interval-valued expectations and sets of probability distributions: Properties and algorithms

Kuznetsov independence of variables X and Y means that, for any pair of bounded functions f(X) and g(Y), E[f(X)g(Y)]=E[f(X)] *times* E[g(Y)], where E[.] denotes interval-valued expectation and *times* denotes interval multiplication. We present properties of Kuznetsov independence for several variables, and connect it with other concepts of independence in the literature; in particular we show that strong extensions are always included in sets of probability distributions whose lower and upper expectations satisfy Kuznetsov independence. We introduce an algorithm that computes lower expectations subject to judgments of Kuznetsov independence by mixing column generation techniques with nonlinear programming. Finally, we define a concept of conditional Kuznetsov independence, and study its graphoid properties.

Approximate credal network updating by linear programming with applications to decision making

Credal nets are probabilistic graphical models which extend Bayesian nets to cope with sets of distributions. An algorithm for approximate credal network updating is presented. The problem in its general formulation is a multilinear optimization task, which can be linearized by an appropriate rule for fixing all the local models apart from those of a single variable. This simple idea can be iterated and quickly leads to accurate inferences. A transformation is also derived to reduce decision making in credal networks based on the maximality criterion to updating. The decision task is proved to have the same complexity of standard inference, being NPPP-complete for general credal nets and NP-complete for polytrees. Similar results are derived for the E-admissibility criterion. Numerical experiments confirm a good performance of the method.

On the complexity of solving polytree-shaped limited memory influence diagrams with binary variables

Influence diagrams are intuitive and concise representations of structured decision problems. When the problem is non-Markovian, an optimal strategy can be exponentially large in the size of the diagram. We can avoid the inherent intractability by constraining the size of admissible strategies, giving rise to limited memory influence diagrams. A valuable question is then how small do strategies need to be to enable efficient optimal planning. Arguably, the smallest strategies one can conceive simply prescribe an action for each time step, without considering past decisions or observations. Previous work has shown that finding such optimal strategies even for polytree-shaped diagrams with ternary variables and a single value node is NP-hard, but the case of binary variables was left open. In this paper we address such a case, by first noting that optimal strategies can be obtained in polynomial time for polytree-shaped diagrams with binary variables and a single value node. We then show that the same problem is NP-hard if the diagram has multiple value nodes. These two results close the fixed-parameter complexity analysis of optimal strategy selection in influence diagrams parametrized by the shape of the diagram, the number of value nodes and the maximum variable cardinality.