X2K

X2K infers upstream transcription factors and kinases that explain genome-wide gene expression changes by integrating ChIP-seq/chip, position weight matrices (PWMs), protein-protein interactions, and kinase-substrate phosphorylation data.

Key Features:

• Integration of Diverse Data Types: X2K combines ChIP-seq/chip data with PWMs, protein-protein interaction networks, and kinase-substrate phosphorylation reactions to link gene expression signatures to upstream regulators.
• Identification of Upstream Regulators: X2K identifies transcription factors and kinases likely responsible for observed mRNA expression changes.
• Validation Across Diverse Applications: X2K has been applied to identify drug targets of FDA-approved drugs by analyzing mRNA expression changes following drug perturbations, map regulatory landscapes of stem cells and their progeny, profile upstream mechanisms in breast cancer tumors, and detect pathways in hepatic stellate cells and hippocampal neurons.
• Advancement of Cell Signaling Understanding: X2K reconstructs regulatory networks to reveal cell signaling mechanisms underlying drug mechanisms of action, cellular differentiation, and disease progression.

Scientific Applications:

• Drug Discovery and Development: Identifying potential drug targets and elucidating mechanisms of action through analysis of mRNA expression changes following drug perturbations.
• Cancer Research: Profiling upstream regulatory mechanisms in breast cancer tumors to inform tumor biology and therapeutic strategies.
• Stem Cell Biology: Mapping transcriptional regulatory networks during stem cell differentiation and in progeny cells.
• Neuroscience: Analyzing signaling pathways and upstream regulators in hippocampal neurons.

Methodology:

Integration of ChIP-seq/chip and PWM-based transcription factor binding mapping, overlay of protein-protein interaction networks, incorporation of kinase-substrate phosphorylation relationships, and analysis of mRNA expression changes following perturbations to infer upstream transcription factors and kinases.