DOSCHEDA: a web application for interactive chemoproteomics data analysis

Abstract

Background. Mass Spectrometry (MS) based chemoproteomics has recently become a main tool to identify and quantify cellular target protein interactions with ligands/drugs in drug discovery. The complexity associated with these new types of data requires scientists with a limited computational background to perform systematic data quality controls as well as to visualize the results derived from the analysis to enable rapid decision making. To date, there are no readily accessible platforms specifically designed for chemoproteomics data analysis. Results. We developed a Shiny-based web application named DOSCHEDA (Down Stream Chemoproteomics Data Analysis) to assess the quality of chemoproteomics experiments, to filter peptide intensities based on linear correlations between replicates, and to perform statistical analysis based on the experimental design. In order to increase its accessibility, DOSCHEDA is designed to be used with minimal user input and it does not require programming knowledge. Typical inputs can be protein fold changes or peptide intensities obtained from Proteome Discover, MaxQuant or other similar software. DOSCHEDA aggregates results from bioinformatics analyses performed on the input dataset into a dynamic interface, it encompasses interactive graphics and enables customized output reports. Conclusions. DOSCHEDA is implemented entirely in R language. It can be launched by any system with R installed, including Windows, Mac OS and Linux distributions. DOSCHEDA is hosted on a shiny-server at https://doscheda.shinyapps.io/doscheda and is also available as a Bioconductor package (http://www.bioconductor.org/).

Development of a Novel B-Cell Lymphoma 6 (BCL6) PROTAC To Provide Insight into Small Molecule Targeting of BCL6

“…(D) Impact of CP and PP on the proteome. Chemical proteomics data have been analyzed with DOSCHEDA and plotted as average fold change versus P value for proteins quantified. BCL6 (green), CK2 subunits (CSNK2A1, CSNK2A2, CSNK2B), and CK2 binding partners (EIF3J, DEK) are highlighted on each plot.…”

Chemical Biology Approaches Confirm MCT4 as the Therapeutic Target of a Cellular Optimized Hit

“…Confirmation of direct target engagement via in-cell chemical proteomic experiments at concentrations 1, 10, and 30 μM of AZ1422 with 1 μM fixed concentration of photoprobe 1 . Data were analyzed using DOSCHEDA . Increased fold change upon an increased dose of AZ1422 is indicative of MCT4-specific interactions.…”

Mechanistic Insights into a CDK9 Inhibitor Via Orthogonal Proteomics Methods

“…Chemoproteomic and KAT pull-down data were analyzed using the Down Stream Chemoproteomics Data Analysis (DOSCHEDA) program. 26 Briefly, the data were taken directly from Proteome Discoverer using both linear and nonlinear models to provide a ranking of the protein(s) most competed and to generate the sigmoidal concentration response curves. Proteins passing cutoff criteria q < 0.01 (Benjamini-Hochberg corrected p-values) were considered as significant hits.…”