The Gene Expression Deconvolution Interactive Tool (GEDIT): Accurate Cell Type Quantification from Gene Expression Data

Abstract

The cell type composition of heterogeneous tissue samples can be a critical variable in both clinical and laboratory settings. However, current experimental methods of cell type quantification (e.g. cell flow cytometry) are costly, time consuming, and can introduce bias. Computational approaches that infer cell type abundance from expression data offer an alternate solution. While these methods have gained popularity, most are limited to predicting hematopoietic cell types and do not produce accurate predictions for stromal cell types. Many of these methods are also limited to particular platforms, whether RNA-seq or specific microarrays. We present the Gene Expression Deconvolution Interactive Tool (GEDIT), a tool that overcomes these limitations, compares favorably with existing methods, and provides superior versatility. Using both simulated and experimental data, we extensively evaluate the performance of GEDIT and demonstrate that it returns robust results under a wide variety of conditions. These conditions include a variety of platforms (microarray and RNA-seq), tissue types (blood and stromal), and species (human and mouse). Finally, we provide reference data from eight sources spanning a wide variety of stromal and hematopoietic types in both human and mouse. This reference database allows the user to obtain estimates for a wide variety of tissue samples without having to provide their own data. GEDIT also accepts user submitted reference data, thus allowing the estimation of any cell type or subtype, provided that reference data is available. Author SummaryThe Gene Expression Deconvolution Interactive Tool (GEDIT) is a robust and accurate tool that uses gene expression data to estimate cell type abundances. Extensive testing on a variety of tissue types and technological platforms demonstrates that GEDIT provides greater versatility than other cell type deconvolution tools. GEDIT utilizes reference data describing the expression profile of purified cell types, and we provide in the software package a library of reference matrices from various sources. GEDIT is also flexible and allows the user to supply custom reference matrices. A GUI interface for GEDIT is available at http://webtools.mcdb.ucla.edu/, and source code and reference matrices are available at https://github.com/BNadel/GEDIT.