A geometric interpretation of the permutation pp-value and its application in eQTL studies

Permutation $p$-values have been widely used to assess the significance of linkage or association in genetic studies. However, the application in large-scale studies is hindered by a heavy computational burden. We propose a geometric interpretation of permutation $p$-values, and based on this geometric interpretation, we develop an efficient permutation $p$-value estimation method in the context of regression with binary predictors. An application to a study of gene expression quantitative trait loci (eQTL) shows that our method provides reliable estimates of permutation $p$-values while requiring less than 5% of the computational time compared with direct permutations. In fact, our method takes a constant time to estimate permutation $p$-values, no matter how small the $p$-value. Our method enables a study of the relationship between nominal $p$-values and permutation $p$-values in a wide range, and provides a geometric perspective on the effective number of independent tests.Comment: Published in at http://dx.doi.org/10.1214/09-AOAS298 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

RGFGA: An efficient representation and crossover for grouping genetic algorithms

There is substantial research into genetic algorithms that are used to group large numbers of objects into mutually exclusive subsets based upon some fitness function. However, nearly all methods involve degeneracy to some degree. We introduce a new representation for grouping genetic algorithms, the restricted growth function genetic algorithm, that effectively removes all degeneracy, resulting in a more efficient search. A new crossover operator is also described that exploits a measure of similarity between chromosomes in a population. Using several synthetic datasets, we compare the performance of our representation and crossover with another well known state-of-the-art GA method, a strawman optimisation method and a well-established statistical clustering algorithm, with encouraging results

Factorial graphical lasso for dynamic networks

Dynamic networks models describe a growing number of important scientific processes, from cell biology and epidemiology to sociology and finance. There are many aspects of dynamical networks that require statistical considerations. In this paper we focus on determining network structure. Estimating dynamic networks is a difficult task since the number of components involved in the system is very large. As a result, the number of parameters to be estimated is bigger than the number of observations. However, a characteristic of many networks is that they are sparse. For example, the molecular structure of genes make interactions with other components a highly-structured and therefore sparse process. Penalized Gaussian graphical models have been used to estimate sparse networks. However, the literature has focussed on static networks, which lack specific temporal constraints. We propose a structured Gaussian dynamical graphical model, where structures can consist of specific time dynamics, known presence or absence of links and block equality constraints on the parameters. Thus, the number of parameters to be estimated is reduced and accuracy of the estimates, including the identification of the network, can be tuned up. Here, we show that the constrained optimization problem can be solved by taking advantage of an efficient solver, logdetPPA, developed in convex optimization. Moreover, model selection methods for checking the sensitivity of the inferred networks are described. Finally, synthetic and real data illustrate the proposed methodologies.Comment: 30 pp, 5 figure

Evidence against the Detectability of a Hippocampal Place Code Using Functional Magnetic Resonance Imaging

Individual hippocampal neurons selectively increase their firing rates in specific spatial locations. As a population, these neurons provide a decodable representation of space that is robust against changes to sensory- and path-related cues. This neural code is sparse and distributed, theoretically rendering it undetectable with population recording methods such as functional magnetic resonance imaging (fMRI). Existing studies nonetheless report decoding spatial codes in the human hippocampus using such techniques. Here we present results from a virtual navigation experiment in humans in which we eliminated visual- and path-related confounds and statistical limitations present in existing studies, ensuring that any positive decoding results would represent a voxel-place code. Consistent with theoretical arguments derived from electrophysiological data and contrary to existing fMRI studies, our results show that although participants were fully oriented during the navigation task, there was no statistical evidence for a place code

Consensus clustering and functional interpretation of gene-expression data

Microarray analysis using clustering algorithms can suffer from lack of inter-method consistency in assigning related gene-expression profiles to clusters. Obtaining a consensus set of clusters from a number of clustering methods should improve confidence in gene-expression analysis. Here we introduce consensus clustering, which provides such an advantage. When coupled with a statistically based gene functional analysis, our method allowed the identification of novel genes regulated by NFκB and the unfolded protein response in certain B-cell lymphomas