ARTO

ARTO analyzes genome-wide DNA replication timing data to estimate time-of-replication (ToR) at each genomic locus and to characterize replication domains for studies of replication timing and chromatin organization.

Key Features:

• Signal processing methodology: Fits a constant piece-wise linear curve to raw time-of-replication (ToR) measurement signals to estimate ToR values at each genomic location.
• Classification of replication regions: Distinguishes Constant Time of Replication (CTR) regions and Temporal Transition Regions (TTR), where CTRs reflect rapid replication from multiple origin activation and TTRs reflect slower propagation.
• Genome-wide profiling: Processes large-scale ToR datasets from multiple organisms, including mouse and human, for comprehensive genome-wide replication timing analysis.
• Plasticity analysis: Detects tissue-specific ToR differences affecting ~10–25% of the genome and activity-type variations in up to ~30% of probes across samples.
• Integration with chromatin structure: Integrates ToR profiles with chromatin organization characteristics and identifies associations with repressive chromatin marks, chromatin compactness, and proximity to the nuclear envelope distinguishing TTRs from CTRs.
• Validation: Reports robust algorithm performance validated through extensive testing for accurate ToR assignment and region classification.

Scientific Applications:

• Understanding replication dynamics: Mapping replication timing across genomes to investigate how temporal replication programs influence genome stability and function.
• Tissue-specific replication patterns: Identifying cell- and tissue-specific ToR variations to study replication program plasticity during differentiation and across tissues.
• Chromatin organization studies: Correlating replication timing with chromatin marks and structural features to explore relationships between replication, chromatin architecture, and epigenetic regulation.

Methodology:

Processes raw ToR measurement signals by fitting a constant piece-wise linear curve to assign a ToR value per genomic locus, categorizes loci into CTRs or TTRs based on replication activity type, and integrates ToR profiles with chromatin organization characteristics; operations are applicable to large-scale datasets (e.g., human and mouse).