SUMMARY: We developed the variant-Set Test for Association using Annotation infoRmation (STAAR) workflow description language (WDL) workflow to facilitate the analysis of rare variants in whole genome sequencing association studies. The open-access STAAR workflow written in the WDL allows a user to perform rare variant testing for both gene-centric and genetic region approaches, enabling genome-wide, candidate and conditional analyses. It incorporates functional annotations into the workflow as introduced in the STAAR method in order to boost the rare variant analysis power. This tool was specifically developed and optimized to be implemented on cloud-based platforms such as BioData Catalyst Powered by Terra. It provides easy-to-use functionality for rare variant analysis that can be incorporated into an exhaustive whole genome sequencing analysis pipeline. AVAILABILITY AND IMPLEMENTATION: The workflow is freely available from https://dockstore.org/workflows/github.com/sheilagaynor/STAAR_workflow. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

SUMMARY: Amidst the continuing spread of coronavirus disease-19 (COVID-19), real-time data analysis and visualization remain critical the general public to track the pandemic's impact and to inform policy making by officials. Multiple metrics permit the evaluation of the spread, infection and mortality of infectious diseases. For example, numbers of new cases and deaths provide easily interpretable measures of absolute impact within a given population and time frame, while the effective reproduction rate provides an epidemiological measure of the rate of spread. By evaluating multiple metrics concurrently, users can leverage complementary insights into the impact and current state of the pandemic when formulating prevention and safety plans for oneself and others. We describe COVID-19 Spread Mapper, a unified framework for estimating and quantifying the uncertainty in the smoothed daily effective reproduction number, case rate and death rate in a region using log-linear models. We apply this framework to characterize COVID-19 impact at multiple geographic resolutions, including by US county and state as well as by country, demonstrating the variation across resolutions and the need for harmonized efforts to control the pandemic. We provide an open-source online dashboard for real-time analysis and visualization of multiple key metrics, which are critical to evaluate the impact of COVID-19 and make informed policy decisions. AVAILABILITY AND IMPLEMENTATION: Our model and tool are publicly available as implemented in R and hosted at https://metrics.covid19-analysis.org/. The source code is freely available from https://github.com/lin-lab/COVID19-Rt and https://github.com/lin-lab/COVID19-Viz. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

MOTIVATION: Cancer genomics studies frequently aim to identify genes that are differentially expressed between clinically distinct patient subgroups, generally by testing single genes one at a time. However, the results of any individual transcriptomic study are often not fully reproducible. A particular challenge impeding statistical analysis is the difficulty of distinguishing between differential expression comprising part of the genomic disease etiology and that induced by downstream effects. More robust analytical approaches that are well-powered to detect potentially causative genes, are less prone to discovering spurious associations, and can deliver reproducible findings across different studies are needed. RESULTS: We propose a set-based procedure for testing of differential expression and show that this set-based approach can produce more robust results by aggregating information across multiple, correlated genomic markers. Specifically, we adapt the Generalized Berk-Jones statistic to test for the transcription factors that may contribute to the progression of estrogen receptor positive breast cancer. We demonstrate the ability of our method to produce reproducible findings by applying the same analysis to 21 publicly available datasets, producing a similar list of significant transcription factors across most studies. Our Generalized Berk-Jones approach produces results that show improved consistency over three set-based testing algorithms: Generalized Higher Criticism, Gene Set Analysis and Gene Set Enrichment Analysis. AVAILABILITY AND IMPLEMENTATION: Data are in the MetaGxBreast R package. Code is available at github.com/ryanrsun/gaynor_sun_GBJ_breast_cancer. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.