MICMIC

MICMIC identifies genome-wide DNA methylation patterns in distal regulatory regions that causally influence tumorigenesis by linking methylation changes to transcription factor activity and tumor suppressor gene inactivation.

Key Features:

• Genome-Wide Analysis: MICMIC systematically identifies DNA methylation across distal genomic regions, focusing on loci with putative causal impacts on tumorigenesis.
• Aberrant Promoter Methylation: The approach accounts for aberrant promoter methylation as a prevalent mechanism leading to tumor suppressor gene inactivation in cancer.
• Integration with Transcription Factor Networks: MICMIC integrates methylation data with oncogenic and lineage-specific transcription factor activity to elucidate alterations in tumor-subtype core regulatory circuitry.
• Validation through Epigenetic Editing: Predicted causal methylation sites are validated experimentally using dCas9-based epigenetic editing to confirm functional effects.

Scientific Applications:

• Tumor Suppressor Inactivation: Identification of methylation events that silence tumor suppressor genes to provide mechanistic insight into cancer development.
• Transcription Factor Interactions: Elucidation of how transcription factors shape the methylation landscape across different cancers.
• Common Architectural Insights: Analysis of enhancer methylation and regulatory networks to reveal convergent gene regulatory architectures across multiple cancer types.

Methodology:

MICMIC analyzes genome-wide DNA methylation data, integrates it with transcription factor binding/activity profiles, and performs causal analysis to identify methylation events in distal regulatory regions that influence tumorigenesis.