xHeinz

xHeinz identifies active subnetwork modules conserved between two species to interpret differential high-throughput molecular profile measurements and generate hypotheses about conserved cellular processes.

Key Features:

• Integrative network analysis: Leverages species-specific interaction networks together with differential high-throughput molecular profile measurements to detect biologically relevant subnetworks.
• Conservation analysis: Finds sets of genes that induce connected subnetworks in each species and contain a significant number of orthologous genes to establish conservation across species.
• Mathematical modeling: Defines active subnetwork modules conserved between two species using an explicit mathematical model to formalize conservation and activity criteria.
• Algorithmic approach: Employs a branch-and-cut algorithm capable of finding provably optimal or near-optimal solutions for the formulated optimization problem.
• Flexible notion of conservation: Incorporates a flexible conservation concept to enhance biological interpretability of identified modules across species.

Scientific Applications:

• Th17 T cell differentiation: Applied to study mechanisms underlying Th17 T cell differentiation in mouse and human.
• Conserved immunity and autoimmunity processes: Used to analyze conserved biological processes related to anti-microbial immunity and autoimmune diseases.

Methodology:

Uses a mathematical model to define conserved active subnetwork modules; identifies gene sets that form connected subnetworks within species-specific interaction networks; assesses differential behavior from high-throughput molecular profiles; enforces conservation by requiring orthologous genes; and optimizes module selection using a branch-and-cut algorithm to produce provably optimal or near-optimal solutions.