urPTMdb/TeaProt: Upstream and Downstream Proteomics Analysis

We have developed
the underrepresented post-translational modification
(PTM) database (urPTMdb), a PTM gene set database to accelerate the
discovery of enriched protein modifications in experimental data.
urPTMdb provides curated lists of proteins reported to be substrates
of underrepresented modifications. Their enrichment in proteomics
datasets can reveal unexpected PTM regulations. urPTMdb can be implemented
in existing workflows, or used in TeaProt, an online Shiny tool that
integrates upstream transcription factor enrichment analysis with
downstream pathway analysis through an easy-to-use interactive interface.
TeaProt annotates user-uploaded data with drug–gene interactions,
subcellular localizations, phenotypic functions, gene–disease
associations, and enzyme–gene interactions. TeaProt enables
gene set enrichment analysis (GSEA) to discover enrichments in gene
sets from various resources, including MSigDB, CHEA, and urPTMdb.
We demonstrate the utility of urPTMdb and TeaProt through the analysis
of a previously published Western diet-induced remodeling of the tongue
proteome, which revealed altered cellular processes associated with
energy metabolism, interferon alpha/gamma response, adipogenesis,
HMGylation substrate enrichment, and transcription regulation through
PPARG and CEBPA. Additionally, we analyzed the interactome of ADP-ribose
glycohydrolase TARG1, a key enzyme that removes mono-ADP-ribosylation.
This analysis identified an enrichment of ADP-ribosylation, ribosomal
proteins, and proteins localized in the nucleoli and endoplasmic reticulum.
TeaProt and urPTMdb are accessible at https://tea.coffeeprot.com/.