Searching Data: A Review of Observational Data Retrieval Practices in Selected Disciplines

A cross-disciplinary examination of the user behaviours involved in seeking and evaluating data is surprisingly absent from the research data discussion. This review explores the data retrieval literature to identify commonalities in how users search for and evaluate observational research data. Two analytical frameworks rooted in information retrieval and science technology studies are used to identify key similarities in practices as a first step toward developing a model describing data retrieval

Principles for the post-GWAS functional characterisation of risk loci

Several challenges lie ahead in assigning functionality to susceptibility SNPs. For example, most effect sizes are small relative to effects seen in monogenic diseases, with per allele odds ratios usually ranging from 1.15 to 1.3. It is unclear whether current molecular biology methods have enough resolution to differentiate such small effects. Our objective here is therefore to provide a set of recommendations to optimize the allocation of effort and resources in order maximize the chances of elucidating the functional contribution of specific loci to the disease phenotype. It has been estimated that 88% of currently identified disease-associated SNP are intronic or intergenic. Thus, in this paper we will focus our attention on the analysis of non-coding variants and outline a hierarchical approach for post-GWAS functional studies

A Multiple Hypothesis Testing Approach to Low-Complexity Subspace Unmixing

Subspace-based signal processing traditionally focuses on problems involving a few subspaces. Recently, a number of problems in different application areas have emerged that involve a significantly larger number of subspaces relative to the ambient dimension. It becomes imperative in such settings to first identify a smaller set of active subspaces that contribute to the observation before further processing can be carried out. This problem of identification of a small set of active subspaces among a huge collection of subspaces from a single (noisy) observation in the ambient space is termed subspace unmixing. This paper formally poses the subspace unmixing problem under the parsimonious subspace-sum (PS3) model, discusses connections of the PS3 model to problems in wireless communications, hyperspectral imaging, high-dimensional statistics and compressed sensing, and proposes a low-complexity algorithm, termed marginal subspace detection (MSD), for subspace unmixing. The MSD algorithm turns the subspace unmixing problem for the PS3 model into a multiple hypothesis testing (MHT) problem and its analysis in the paper helps control the family-wise error rate of this MHT problem at any level $\alpha \in [0,1]$ under two random signal generation models. Some other highlights of the analysis of the MSD algorithm include: (i) it is applicable to an arbitrary collection of subspaces on the Grassmann manifold; (ii) it relies on properties of the collection of subspaces that are computable in polynomial time; and ($iii$) it allows for linear scaling of the number of active subspaces as a function of the ambient dimension. Finally, numerical results are presented in the paper to better understand the performance of the MSD algorithm.Comment: Submitted for journal publication; 33 pages, 14 figure

1st INCF Workshop on Sustainability of Neuroscience Databases

The goal of the workshop was to discuss issues related to the sustainability of neuroscience databases, identify problems and propose solutions, and formulate recommendations to the INCF. The report summarizes the discussions of invited participants from the neuroinformatics community as well as from other disciplines where sustainability issues have already been approached. The recommendations for the INCF involve rating, ranking, and supporting database sustainability

Molecular Inverse Comorbidity between Alzheimer’s Disease and Lung Cancer: New Insights from Matrix Factorization

International audienceMatrix factorization (MF) is an established paradigm for large-scale biological data analysis with tremendous potential in computational biology. Here, we challenge MF in depicting the molecular bases of epidemiologically described disease-disease (DD) relationships. As a use case, we focus on the inverse comorbidity association between Alzheimer's disease (AD) and lung cancer (LC), described as a lower than expected probability of developing LC in AD patients. To this day, the molecular mechanisms underlying DD relationships remain poorly explained and their better characterization might offer unprecedented clinical opportunities. To this goal, we extend our previously designed MF-based framework for the molecular characterization of DD relationships. Considering AD-LC inverse comorbidity as a case study, we highlight multiple molecular mechanisms, among which we confirm the involvement of processes related to the immune system and mitochondrial metabolism. We then distinguish mechanisms specific to LC from those shared with other cancers through a pan-cancer analysis. Additionally, new candidate molecular players, such as estrogen receptor (ER), cadherin 1 (CDH1) and histone deacetylase (HDAC), are pinpointed as factors that might underlie the inverse relationship, opening the way to new investigations. Finally, some lung cancer subtype-specific factors are also detected, also suggesting the existence of heterogeneity across patients in the context of inverse comorbidity

High-Dimensional Joint Estimation of Multiple Directed Gaussian Graphical Models

We consider the problem of jointly estimating multiple related directed acyclic graph (DAG) models based on high-dimensional data from each graph. This problem is motivated by the task of learning gene regulatory networks based on gene expression data from different tissues, developmental stages or disease states. We prove that under certain regularity conditions, the proposed $\ell_0$-penalized maximum likelihood estimator converges in Frobenius norm to the adjacency matrices consistent with the data-generating distributions and has the correct sparsity. In particular, we show that this joint estimation procedure leads to a faster convergence rate than estimating each DAG model separately. As a corollary, we also obtain high-dimensional consistency results for causal inference from a mix of observational and interventional data. For practical purposes, we propose \emph{jointGES} consisting of Greedy Equivalence Search (GES) to estimate the union of all DAG models followed by variable selection using lasso to obtain the different DAGs, and we analyze its consistency guarantees. The proposed method is illustrated through an analysis of simulated data as well as epithelial ovarian cancer gene expression data

Many-Task Computing and Blue Waters

This report discusses many-task computing (MTC) generically and in the context of the proposed Blue Waters systems, which is planned to be the largest NSF-funded supercomputer when it begins production use in 2012. The aim of this report is to inform the BW project about MTC, including understanding aspects of MTC applications that can be used to characterize the domain and understanding the implications of these aspects to middleware and policies. Many MTC applications do not neatly fit the stereotypes of high-performance computing (HPC) or high-throughput computing (HTC) applications. Like HTC applications, by definition MTC applications are structured as graphs of discrete tasks, with explicit input and output dependencies forming the graph edges. However, MTC applications have significant features that distinguish them from typical HTC applications. In particular, different engineering constraints for hardware and software must be met in order to support these applications. HTC applications have traditionally run on platforms such as grids and clusters, through either workflow systems or parallel programming systems. MTC applications, in contrast, will often demand a short time to solution, may be communication intensive or data intensive, and may comprise very short tasks. Therefore, hardware and software for MTC must be engineered to support the additional communication and I/O and must minimize task dispatch overheads. The hardware of large-scale HPC systems, with its high degree of parallelism and support for intensive communication, is well suited for MTC applications. However, HPC systems often lack a dynamic resource-provisioning feature, are not ideal for task communication via the file system, and have an I/O system that is not optimized for MTC-style applications. Hence, additional software support is likely to be required to gain full benefit from the HPC hardware