Gene expression in large pedigrees: analytic approaches.

BackgroundWe currently have the ability to quantify transcript abundance of messenger RNA (mRNA), genome-wide, using microarray technologies. Analyzing genotype, phenotype and expression data from 20 pedigrees, the members of our Genetic Analysis Workshop (GAW) 19 gene expression group published 9 papers, tackling some timely and important problems and questions. To study the complexity and interrelationships of genetics and gene expression, we used established statistical tools, developed newer statistical tools, and developed and applied extensions to these tools.MethodsTo study gene expression correlations in the pedigree members (without incorporating genotype or trait data into the analysis), 2 papers used principal components analysis, weighted gene coexpression network analysis, meta-analyses, gene enrichment analyses, and linear mixed models. To explore the relationship between genetics and gene expression, 2 papers studied expression quantitative trait locus allelic heterogeneity through conditional association analyses, and epistasis through interaction analyses. A third paper assessed the feasibility of applying allele-specific binding to filter potential regulatory single-nucleotide polymorphisms (SNPs). Analytic approaches included linear mixed models based on measured genotypes in pedigrees, permutation tests, and covariance kernels. To incorporate both genotype and phenotype data with gene expression, 4 groups employed linear mixed models, nonparametric weighted U statistics, structural equation modeling, Bayesian unified frameworks, and multiple regression.Results and discussionRegarding the analysis of pedigree data, we found that gene expression is familial, indicating that at least 1 factor for pedigree membership or multiple factors for the degree of relationship should be included in analyses, and we developed a method to adjust for familiality prior to conducting weighted co-expression gene network analysis. For SNP association and conditional analyses, we found FaST-LMM (Factored Spectrally Transformed Linear Mixed Model) and SOLAR-MGA (Sequential Oligogenic Linkage Analysis Routines -Major Gene Analysis) have similar type 1 and type 2 errors and can be used almost interchangeably. To improve the power and precision of association tests, prior knowledge of DNase-I hypersensitivity sites or other relevant biological annotations can be incorporated into the analyses. On a biological level, eQTL (expression quantitative trait loci) are genetically complex, exhibiting both allelic heterogeneity and epistasis. Including both genotype and phenotype data together with measurements of gene expression was found to be generally advantageous in terms of generating improved levels of significance and in providing more interpretable biological models.ConclusionsPedigrees can be used to conduct analyses of and enhance gene expression studies

Curriculum Guidelines for Undergraduate Programs in Data Science

The Park City Math Institute (PCMI) 2016 Summer Undergraduate Faculty Program met for the purpose of composing guidelines for undergraduate programs in Data Science. The group consisted of 25 undergraduate faculty from a variety of institutions in the U.S., primarily from the disciplines of mathematics, statistics and computer science. These guidelines are meant to provide some structure for institutions planning for or revising a major in Data Science

On a Proper Meta-Analytic Model for Correlations

Combining statistical information across studies is a standard research tool in applied psychology. The most common approach in applied psychology is the fixed effects model. The fixed-effects approach assumes that individual study characteristics such as treatment conditions, study context, or individual differences do not influence study effect sizes. That is, that the majority of the differences between the effect sizes of different studies can be explained by sampling error alone. We critique the fixed-effects methodology for correlations and propose an advancement, the random-effects model, that ameliorates problems imposed by fixed-effects models. The random-effects approach explicitly incorporates between-study differences in data analysis and provides estimates of how those study characteristics influence the relationships among constructs of interest. Because they can model the influence of study characteristics, we assert that random-effects models have advantages for psychological research. Parameter estimates of both models are compared and evidence in favor of the random-effects approach is presented

ALOJA: A framework for benchmarking and predictive analytics in Hadoop deployments

This article presents the ALOJA project and its analytics tools, which leverages machine learning to interpret Big Data benchmark performance data and tuning. ALOJA is part of a long-term collaboration between BSC and Microsoft to automate the characterization of cost-effectiveness on Big Data deployments, currently focusing on Hadoop. Hadoop presents a complex run-time environment, where costs and performance depend on a large number of configuration choices. The ALOJA project has created an open, vendor-neutral repository, featuring over 40,000 Hadoop job executions and their performance details. The repository is accompanied by a test-bed and tools to deploy and evaluate the cost-effectiveness of different hardware configurations, parameters and Cloud services. Despite early success within ALOJA, a comprehensive study requires automation of modeling procedures to allow an analysis of large and resource-constrained search spaces. The predictive analytics extension, ALOJA-ML, provides an automated system allowing knowledge discovery by modeling environments from observed executions. The resulting models can forecast execution behaviors, predicting execution times for new configurations and hardware choices. That also enables model-based anomaly detection or efficient benchmark guidance by prioritizing executions. In addition, the community can benefit from ALOJA data-sets and framework to improve the design and deployment of Big Data applications.This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 639595). This work is partially supported by the Ministry of Economy of Spain under contracts TIN2012-34557 and 2014SGR1051.Peer ReviewedPostprint (published version

A Relational Hyperlink Analysis of an Online Social Movement

In this paper we propose relational hyperlink analysis (RHA) as a distinct approach for empirical social science research into hyperlink networks on the World Wide Web. We demonstrate this approach, which employs the ideas and techniques of social network analysis (in particular, exponential random graph modeling), in a study of the hyperlinking behaviors of Australian asylum advocacy groups. We show that compared with the commonly-used hyperlink counts regression approach, relational hyperlink analysis can lead to fundamentally different conclusions about the social processes underpinning hyperlinking behavior. In particular, in trying to understand why social ties are formed, counts regressions may over-estimate the role of actor attributes in the formation of hyperlinks when endogenous, purely structural network effects are not taken into account. Our analysis involves an innovative joint use of two software programs: VOSON, for the automated retrieval and processing of considerable quantities of hyperlink data, and LPNet, for the statistical modeling of social network data. Together, VOSON and LPNet enable new and unique research into social networks in the online world, and our paper highlights the importance of complementary research tools for social science research into the web