MOTIVATION: High-throughput fluorescent microscopy is a popular class of techniques for studying tissues and cells through automated imaging and feature extraction of hundreds to thousands of samples. Like other high-throughput assays, these approaches can suffer from unwanted noise and technical artifacts that obscure the biological signal. In this work, we consider how an experimental design incorporating multiple levels of replication enables the removal of technical artifacts from such image-based platforms. RESULTS: We develop a general approach to remove technical artifacts from high-throughput image data that leverages an experimental design with multiple levels of replication. To illustrate the methods, we consider microenvironment microarrays (MEMAs), a high-throughput platform designed to study cellular responses to microenvironmental perturbations. In application to MEMAs, our approach removes unwanted spatial artifacts and thereby enhances the biological signal. This approach has broad applicability to diverse biological assays. AVAILABILITY AND IMPLEMENTATION: Raw data are on synapse (syn2862345), analysis code is on github: gjhunt/mema_norm, a reproducible Docker image is available on dockerhub: gjhunt/mema_norm. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

MOTIVATION: Cell type composition of tissues is important in many biological processes. To help understand cell type composition using gene expression data, methods of estimating (deconvolving) cell type proportions have been developed. Such estimates are often used to adjust for confounding effects of cell type in differential expression analysis (DEA). RESULTS: We propose dtangle, a new cell type deconvolution method. dtangle works on a range of DNA microarray and bulk RNA-seq platforms. It estimates cell type proportions using publicly available, often cross-platform, reference data. We evaluate dtangle on 11 benchmark datasets showing that dtangle is competitive with published deconvolution methods, is robust to outliers and selection of tuning parameters, and is fast. As a case study, we investigate the human immune response to Lyme disease. dtangle's estimates reveal a temporal trend consistent with previous findings and are important covariates for DEA across disease status. AVAILABILITY AND IMPLEMENTATION: dtangle is on CRAN (cran.r-project.org/package=dtangle) or github (dtangle.github.io). SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.