HolistIC

HolistIC predicts double minute (DM) chromosome architectures by integrating whole genome shotgun sequencing (WGS) and Hi-C sequencing data to resolve overlapping amplicon coordinates and characterize acentric extrachromosomal DNA amplifications such as oncogene and drug-resistance gene amplicons in tumor genomes.

Key Features:

• WGS and Hi-C integration: Integrates whole genome shotgun sequencing (WGS) with Hi-C sequencing information for joint structural analysis.
• Multiple DM architecture prediction: Predicts multiple distinct double minute (DM) chromosome architectures, including circular chromatin structures formed from progenitor segments.
• Overlap resolution: Distinguishes and resolves overlapping amplicon coordinates that confound WGS-only methods.
• Extrachromosomal amplification characterization: Characterizes acentric extrachromosomal DNA amplifications, including high-copy oncogene and drug-resistance gene amplicons.
• Tandem dataset analysis: Leverages tandem Hi-C and WGS datasets for improved prediction specificity.
• Validation: Validated on three cancer datasets and a simulated dataset to assess prediction accuracy.

Scientific Applications:

• DM identification: Identification and characterization of double minute (DM) chromosome architectures in tumor genomes.
• Amplicon disambiguation: Disambiguation of overlapping amplicons to improve accuracy of extrachromosomal amplification calls.
• Cancer genomics analysis: Clarification of extrachromosomal amplification structures to support cancer genomics studies and comparative analyses.
• Method benchmarking: Benchmarking and evaluation of DM detection approaches using cancer and simulated datasets.

Methodology:

HolistIC integrates WGS data with Hi-C sequencing information to identify and resolve overlapping amplicon coordinates and predict double minute (DM) chromosome architectures, and it was implemented and evaluated on three cancer datasets and a simulated dataset.