Showing papers by "Siva Sivaganesan published in 2017"
Icahn School of Medicine at Mount Sinai1, University of Miami2, University of Cincinnati3, University of California, San Francisco4, Massachusetts Institute of Technology5, Johns Hopkins University6, Cedars-Sinai Medical Center7, University of California, Irvine8, Broad Institute9, Harvard University10, Oregon Health & Science University11, University of Texas MD Anderson Cancer Center12, City of Hope National Medical Center13, University of Bergen14
TL;DR: The LINCS program focuses on cellular physiology shared among tissues and cell types relevant to an array of diseases, including cancer, heart disease, and neurodegenerative disorders.
Abstract: The Library of Integrated Network-Based Cellular Signatures (LINCS) is an NIH Common Fund program that catalogs how human cells globally respond to chemical, genetic, and disease perturbations. Resources generated by LINCS include experimental and computational methods, visualization tools, molecular and imaging data, and signatures. By assembling an integrated picture of the range of responses of human cells exposed to many perturbations, the LINCS program aims to better understand human disease and to advance the development of new therapies. Perturbations under study include drugs, genetic perturbations, tissue micro-environments, antibodies, and disease-causing mutations. Responses to perturbations are measured by transcript profiling, mass spectrometry, cell imaging, and biochemical methods, among other assays. The LINCS program focuses on cellular physiology shared among tissues and cell types relevant to an array of diseases, including cancer, heart disease, and neurodegenerative disorders. This Perspective describes LINCS technologies, datasets, tools, and approaches to data accessibility and reusability.
300 citations
TL;DR: A Bayesian decision theoretic approach to finding subgroups that have elevated treatment effects and allows subgroups based on both quantitative and categorical covariates irrespective of potential subgroups of interest.
Abstract: We provide a Bayesian decision theoretic approach to finding subgroups that have elevated treatment effects. Our approach separates the modeling of the response variable from the task of subgroup finding and allows a flexible modeling of the response variable irrespective of potential subgroups of interest. We use Bayesian additive regression trees to model the response variable and use a utility function defined in terms of a candidate subgroup and the predicted response for that subgroup. Subgroups are identified by maximizing the expected utility where the expectation is taken with respect to the posterior predictive distribution of the response, and the maximization is carried out over an a priori specified set of candidate subgroups. Our approach allows subgroups based on both quantitative and categorical covariates. We illustrate the approach using simulated data set study and a real data set. Copyright © 2017 John Wiley & Sons, Ltd.
32 citations
TL;DR: A Bayesian approach to subgroup analysis using ANOVA models with multiple covariates, extending an earlier work, that uses a structured algorithm based on the posterior probabilities of the models to determine which subgroup effects to report.
Abstract: We develop a Bayesian approach to subgroup analysis using ANOVA models with multiple covariates, extending an earlier work. We assume a two-arm clinical trial with normally distributed response variable. We also assume that the covariates for subgroup finding are categorical and are a priori specified, and parsimonious easy-to-interpret subgroups are preferable. We represent the subgroups of interest by a collection of models and use a model selection approach to finding subgroups with heterogeneous effects. We develop suitable priors for the model space and use an objective Bayesian approach that yields multiplicity adjusted posterior probabilities for the models. We use a structured algorithm based on the posterior probabilities of the models to determine which subgroup effects to report. Frequentist operating characteristics of the approach are evaluated using simulation. While our approach is applicable in more general cases, we mainly focus on the 2 × 2 case of two covariates each at two levels for ease of presentation. The approach is illustrated using a real data example.
8 citations
TL;DR: In this paper, the authors presented an objective Bayesian estimation approach to the two-period crossover design, which is also known as the carryover effect, and addressed the indeterminacy of the Bayes factor due to the arbitrary constant in the improper prior by assigning a minimally discriminatory value to the constant.
Abstract: Two-period crossover design is one of the commonly used designs in clinical trials. But, the estimation of treatment effect is complicated by the possible presence of carryover effect. It is known that ignoring the carryover effect when it exists can lead to poor estimates of the treatment effect. The classical approach by Grizzle (1965) consists of two stages. First, a preliminary test is conducted on carryover effect. If the carryover effect is significant, analysis is based only on data from period one; otherwise, analysis is based on data from both periods. A Bayesian approach with improper priors was proposed by Grieve (1985) which uses a mixture of two models: a model with carryover effect and another without. The indeterminacy of the Bayes factor due to the arbitrary constant in the improper prior was addressed by assigning a minimally discriminatory value to the constant. In this article, we present an objective Bayesian estimation approach to the two-period crossover design which is also ...