GISPA

GISPA identifies gene sets that match user-defined molecular profiles by integrating multiple genomic data types to produce ranked gene sets and detect potential phenotype drivers.

Key Features:

• Integrated multi-omic analysis: Integrates multiple genomic data types rather than relying solely on intersecting separate analyses.
• User-defined molecular profiles: Allows specification of molecular profiles to guide identification of gene sets that conform to those profiles.
• Class comparison: Compares defined molecular profiles across user-specified classes to find class-specific gene set activity.
• Ranked gene-set output: Produces ranked gene sets aligned with the specified molecular profile to prioritize candidates such as phenotype drivers.
• SISPA sample-centric variant: Provides Sample Integrated Set Profile Analysis (SISPA) to identify groups of samples exhibiting the defined gene-set profile activity.
• Addresses IBI limitations: Designed to overcome limitations of "integrate by intersection" (IBI) approaches that reduce intersection size as more data types are added.

Scientific Applications:

• Gene-centric discovery: Identification and prioritization of genes with specific multi-dimensional molecular profiles as potential phenotype drivers.
• Sample stratification (SISPA): Identification of sample groups that exhibit defined gene-set profile activity for downstream clinical or biological analysis.
• Multiple myeloma studies: Applied to human multiple myeloma (MM) cell lines to recover known and novel targets.
• Clinical trial data analysis: Applied with SISPA to data from the MM coMMpass trial to identify clinically relevant sample groups with profile activity.

Methodology:

Explicitly contrasts with "integrate by intersection" (IBI) approaches that intersect results from separate analyses; enables definition of molecular profiles, comparison of those profiles across classes, integration of multiple genomic data types, generation of ranked gene sets, and a SISPA mode that identifies samples exhibiting the defined profile activity.