PhosphoDisco: A Toolkit for Co-regulated Phosphorylation Module Discovery in Phosphoproteomic Data

Area of Science:

• Oncology
• Molecular Biology
• Bioinformatics

Background:

• Kinases are crucial in cancer pathways and targeted by precision therapies.
• Phosphoproteomics reveals kinase activity, identifying therapeutic targets and biomarkers.
• Identifying co-regulated phosphorylation sites aids in understanding signaling pathways and therapeutic targets, but is experimentally limited.

Purpose of the Study:

• To develop a computational toolkit, PhosphoDisco, for identifying co-regulated phosphorylation modules.
• To address the challenge of defining functionally relevant co-regulated phosphorylation modules from phosphoproteomic data.
• To apply PhosphoDisco to cancer phosphoproteomic data for discovering novel signaling pathways and therapeutic strategies.

Main Methods:

• Developed PhosphoDisco, a computational toolkit for analyzing co-regulated phosphorylation sites.
• Applied PhosphoDisco to tandem mass spectrometry-based phosphoproteomic data from breast and non-small cell lung cancer.
• Utilized identified modules for pathway analysis and tumor classification based on signaling activity.

Main Results:

• Identified canonical and putative novel phosphorylation site modules in breast and lung cancer datasets.
• Discovered a new cell cycle checkpoint module significantly enriched in basal breast cancer.
• Found a module of PRKC isozymes potentially co-regulated by CDK12 in lung cancer.

Conclusions:

• PhosphoDisco effectively identifies co-regulated phosphorylation modules from phosphoproteomic data.
• The identified modules offer insights into active signaling pathways in patient tumors.
• PhosphoDisco facilitates personalized cancer treatment strategies and novel tumor classification based on signaling profiles.