TPP2D

TPP2D performs an FDR-controlled analysis of 2D-TPP experiments by functional analysis of dose-response curves across temperatures to detect ligand-protein interactions from 2D thermal profiles.

Key Features:

• Statistical hypothesis testing on curves: Provides control of the false discovery rate without using preset thresholds that can lead to suboptimal sensitivity/specificity tradeoffs.
• Dose-response curve analysis: Analyzes thermal stability as a function of ligand concentration across a dose range.
• 2D-TPP experiment support: Processes two-dimensional thermal proteome profiling data combining temperature and ligand concentration dimensions.

Scientific Applications:

• Ligand-protein interaction detection: Identifies ligand-binding proteins from dose range thermal proteome profiles in living cells.
• Off-target drug engagement discovery: Detects unexpected drug targets, as demonstrated by identifying that the HDAC8 inhibitor PCI-34051 and its analog BRD-3811 bind to and inhibit leucine aminopeptidase 3.
• Epigenetic drug profiling: Applied to datasets probing epigenetic drugs to characterize their target engagement profiles.
• Metabolite target identification: Used to identify protein targets of endogenous metabolites through thermal profiling.

Methodology:

The method performs statistical hypothesis testing on curves to analyze dose-response relationships across temperatures, implemented as an R package available from Bioconductor.