Extracting Functional Modules from Biological Pathways

It has been proposed that functional modules are the fundamental units of cellular function. Methods to identify these modules have thus far relied on gene expression data or protein-protein interaction (PPI) data, but have a few limitations. We propose a new method, using biological pathway data to identify functional modules, that can potentially overcome these limitations. We also construct a network of these modules using functionally relevant PPI data. This network displays the flow and integration of information between modules and can be used to map cellular function

A nonparametric empirical Bayes approach to covariance matrix estimation

We propose an empirical Bayes method to estimate high-dimensional covariance matrices. Our procedure centers on vectorizing the covariance matrix and treating matrix estimation as a vector estimation problem. Drawing from the compound decision theory literature, we introduce a new class of decision rules that generalizes several existing procedures. We then use a nonparametric empirical Bayes g-modeling approach to estimate the oracle optimal rule in that class. This allows us to let the data itself determine how best to shrink the estimator, rather than shrinking in a pre-determined direction such as toward a diagonal matrix. Simulation results and a gene expression network analysis shows that our approach can outperform a number of state-of-the-art proposals in a wide range of settings, sometimes substantially.Comment: 20 pages, 4 figure

Nonparametric false discovery rate control for identifying simultaneous signals

It is frequently of interest to jointly analyze multiple sequences of multiple tests in order to identify simultaneous signals, defined as features tested in multiple studies whose test statistics are non-null in each. In many problems, however, the null distributions of the test statistics may be complicated or even unknown, and there do not currently exist any procedures that can be employed in these cases. This paper proposes a new nonparametric procedure that can identify simultaneous signals across multiple studies even without knowing the null distributions of the test statistics. The method is shown to asymptotically control the false discovery rate, and in simulations had excellent power and error control. In an analysis of gene expression and histone acetylation patterns in the brains of mice exposed to a conspecific intruder, it identified genes that were both differentially expressed and next to differentially accessible chromatin. The proposed method is available in the R package github.com/sdzhao/ssa

Nonparametric False Discovery Rate Control for Identifying Simultaneous Signals

It is frequently of interest to identify simultaneous signals, defined as features that exhibit statistical significance across each of several independent experiments. For example, genes that are consistently differentially expressed across experiments in different animal species can reveal evolutionarily conserved biological mechanisms. However, in some problems the test statistics corresponding to these features can have complicated or unknown null distributions. This paper proposes a novel nonparametric false discovery rate control procedure that can identify simultaneous signals even without knowing these null distributions. The method is shown, theoretically and in simulations, to asymptotically control the false discovery rate. It was also used to identify genes that were both differentially expressed and proximal to differentially accessible chromatin in the brains of mice exposed to a conspecific intruder. The proposed method is available in the R package github.com/sdzhao/ssa