AmetaRisk

AmetaRisk quantifies colorectal cancer (CRC) metastasis risk by assessing local invasion potential from somatic and germline mutation data.

Key Features:

• Local Invasion Power (LIP): A novel statistical parameter that quantitatively measures the potential of somatic and germline mutations to promote local invasion in CRC.
• Germline versus somatic analysis: Emphasizes the role of innate germline mutations over somatic mutations in driving local invasion.
• Exome-wide bioinformatic analyses: Performs exome-wide analyses using large datasets from public repositories to detect invasion-associated variants.
• Identification of driver variants: Identifies ten potential driver variants associated with tumor cell invasion, including six genes newly associated with CRC metastasis.
• Metastasis resister variant: Detects a variant that acts as a resister against metastasis.
• Logistic regression model: Constructs a logistic regression model using the identified variants to assess risk of early metastasis.

Scientific Applications:

• Mechanistic insights: Uses exome-wide mutation data and LIP to provide mechanistic insight into genetic drivers of local invasion and metastasis in CRC.
• Clinical prioritization: Provides a variant-based risk assessment that can be used to prioritize therapeutic regimens according to individual patient mutation profiles.
• Drug target discovery: Identifies genes and variants associated with metastasis that serve as candidates for novel drug target investigation.

Methodology:

Calculation of Local Invasion Power (LIP); exome-wide bioinformatic analyses of large public-repository datasets to identify driver variants (ten candidates, six novel gene associations and one metastasis-resister); and construction of a logistic regression model using the identified variants for early metastasis risk assessment.