methylclock

methylclock detects and analyzes mosaic loss of chromosome Y (mLOY) across diverse tissues to support studies of its associations with cancer, age-related disorders, and male mortality.

Key Features:

• Integration of Existing Methods: Integrates established mLOY detection methods with a novel approach to enable consistent calling and methodological comparisons in large-scale studies.
• Robust Statistical Modeling: Models a reference population without mLOY and incorporates B-deviation information to improve detection precision.
• Enhanced Detection Accuracy: Validated with experimentally confirmed samples and simulation studies, yielding improved accuracy and increased statistical power for association analyses.
• Tissue-Specific Analysis: Applied to multiple tissue matrices, revealing tissue-dependent detection efficiencies (e.g., ~41% detection in saliva) and enabling longitudinal tracking in blood over a three-year period.
• Gene and Pathway Analysis: Facilitates identification of down-regulated genes on chromosome Y in cancers such as kidney and bladder and supports pathway analyses of mLOY-associated molecular changes in blood samples.

Scientific Applications:

• Epidemiological Studies: Enables large-scale analyses of mLOY prevalence and its associations with cancer, age-related conditions, and male mortality.
• Molecular and Functional Studies: Supports gene-level and pathway analyses to investigate molecular mechanisms linking mLOY to disease phenotypes.

Methodology:

Implemented in R, the approach optimizes reference population modeling, incorporates established mLOY detection methods, and leverages B-deviation data to refine mLOY calls; it has been validated with experimentally confirmed samples and simulation studies.