RCDRank: a web server to prioritize regulated cell death modalities

Area of Science:

• Cellular Biology
• Molecular Biology
• Bioinformatics

Background:

• Regulated cell death (RCD) is crucial for homeostasis and tissue integrity, involving diverse, interacting pathways.
• Understanding the complex interplay and relative importance of RCD modalities in disease is challenging.
• Existing methods struggle to systematically analyze RCD pathway priorities in specific biological contexts.

Purpose of the Study:

• To develop an advanced methodology for systematically analyzing and prioritizing regulated cell death (RCD) pathways.
• To create a user-friendly web application for researchers to explore RCD dynamics.

Main Methods:

• A manually curated collection of gene sets for 18 RCD modes was created.
• Seven gene set enrichment tests were combined using Tippet's p-value approach.
• Robust rank aggregation evaluated pathway consensus, with priorities determined by combined p-value and consensus score.

Main Results:

• A novel approach was developed to systematically rank and analyze 18 well-characterized RCD pathways.
• The method integrates multiple enrichment tests and rank aggregation for robust pathway prioritization.
• The approach was validated in the context of intracranial aneurysms, revealing complex RCD dynamics.

Conclusions:

• A new computational method and web server (RCRank) are available for dissecting complex RCD modalities in specific biological settings.
• The RCRank web server provides a valuable resource for researchers studying cell death pathways.
• This work facilitates a deeper understanding of RCD's role in health and disease.