RCK

RCK reconstructs clone- and haplotype-specific cancer karyotypes from bulk tumor DNA sequencing to resolve chromosomal rearrangements and clonal composition.

Key Features:

• Clone- and haplotype-specific reconstruction: Reconstructs clone- and haplotype-specific karyotypes from bulk tumor sequencing data.
• Evolutionary-constraint-based deconvolution: Uses evolutionary constraints from somatic mutational processes to reduce ambiguity when deconvolving admixed sequencing data.
• Arbitrary-genome mixture modeling: Models mixtures containing an arbitrary number of derived genomes to represent multiple tumor clones.
• Multi-technology sequencing support: Integrates short-read and long-read DNA sequencing data.
• Handling of complex rearrangements and admixture: Addresses extensive chromosomal rearrangements and the admixture of normal cells and cancer subpopulations in tumors.
• Empirical performance: Demonstrated improved inference on 17 primary and metastatic prostate cancer samples by producing karyotypes that better explain sequencing data and align with evolutionary models.

Scientific Applications:

• Karyotype reconstruction from bulk tumors: Recover clone- and haplotype-specific karyotypes from bulk tumor DNA sequencing.
• Intra-tumor heterogeneity analysis: Characterize clonal composition and heterogeneity within tumor samples.
• Interpretation of chromosomal rearrangements: Analyze complex structural rearrangements in cancer genomes.
• Evolutionary analysis and method comparison: Support evolutionary interpretation of somatic mutation processes and comparative evaluation of karyotype inference methods, as shown in a 17-sample prostate cancer study.

Methodology:

RCK computationally deconvolves bulk tumor DNA sequencing (short- and long-read) by modeling mixtures of an arbitrary number of derived genomes and applying evolutionary constraints from somatic mutational processes to reconstruct clone- and haplotype-specific karyotypes.