ShatterProof

ShatterProof detects and quantifies chromothripsis from structural variation calls derived from high-throughput sequencing data to identify and localize chromothriptic events in cancer genomes.

Key Features:

• Input types: Accepts structural variation calls such as translocations, copy-number variations, short insertions, and loss of heterozygosity generated by any algorithm.
• Operational definition: Applies a well-defined operational definition of chromothripsis to standardize detection criteria.
• Statistical prediction: Performs robust statistical tests to predict the presence and precise genomic location of chromothriptic events.
• Biological relevance: Targets chromothripsis events implicated in cancers including bone cancer, SHH-medulloblastoma, acute myeloid leukemia, prostate cancer, colorectal cancer, and small cell lung cancer.
• Computational performance: Implements a low-memory, near-linear time algorithm suitable for large sequencing datasets.

Scientific Applications:

• Cancer genomics: Detection and localization of chromothripsis in tumor genomes across multiple cancer types including bone cancer, SHH-medulloblastoma, acute myeloid leukemia, prostate cancer, colorectal cancer, and small cell lung cancer.
• Clinical cohort analysis: Assessment of matched normal–tumor datasets for chromothriptic events in clinical studies.
• Cross-study comparison: Standardized scoring of chromothripsis to enable comparison of findings across sequencing studies and cohorts.

Methodology:

ShatterProof takes structural variation calls (translocations, copy-number variations, short insertions, loss of heterozygosity), applies a defined operational definition of chromothripsis, and uses robust statistical tests to predict the presence and precise location of chromothriptic events while operating with low memory and near-linear runtime.