Mustache

Mustache detects chromatin loops and other chromatin interactions in Hi-C and Micro-C contact maps to map structural and regulatory genome interactions across genomic distances.

Key Features:

• Scale-space blob detection: Leverages scale-space theory from computer vision to detect blob-shaped structures in contact maps.
• Smoothing kernel parameterization: Parameterizes contact maps by the size of a smoothing kernel to enable multi-scale detection.
• Hi-C and Micro-C compatibility: Operates on both Hi-C and Micro-C contact maps, including high-resolution datasets.
• Detection across genomic distances: Identifies chromatin interactions spanning diverse genomic distance scales via multi-scale analysis.
• Association with regulatory elements: Identified interactions align with CTCF binding sites, enhancers, and promoters.
• Performance on 5 kb maps: Processes 5 kb-resolution human genome contact maps on general-purpose CPUs in minutes per chromosome.
• Increased sensitivity vs HiCCUPS: Detects approximately 2–3 times more chromatin loops than HiCCUPS.
• Reproducibility: Maintains reproducibility across biological replicates.
• Recovery of orthogonal loops: Recovers a larger proportion of known ChIA-PET and HiChIP loops compared to HiCCUPS.
• Micro-C enhanced detection: Shows strong agreement between high-resolution Hi-C and Micro-C, with Micro-C demonstrating enhanced detection capabilities.

Scientific Applications:

• Loop and interaction discovery: Identification of structural chromatin loops and regulatory genome interactions from contact maps.
• Regulatory element mapping: Mapping interactions that involve CTCF, enhancers, and promoters.
• Benchmarking and validation: Comparative sensitivity and recovery assessment against HiCCUPS, ChIA-PET, and HiChIP datasets.
• High-resolution chromatin analysis: Analysis of high-resolution Hi-C and Micro-C datasets for enhanced interaction detection.
• Routine processing of 5 kb maps: Generation of loop calls from 5 kb-resolution human genome contact maps on standard CPU hardware.

Methodology:

Mustache leverages scale-space theory to detect blob-shaped structures in Hi-C and Micro-C contact maps and parameterizes maps by the size of a smoothing kernel to detect chromatin interactions across diverse genomic distances.