Clomial

Clomial is a computational tool to elucidate the clonal composition of tumors, a task of critical importance for understanding cancer prognosis and tailoring therapies. Recognizing that cancers evolve through successive mutations and selection, leading to clonal populations with distinct sizes, mutational profiles, and drug sensitivities, Clomial addresses the complex challenge of deconvolving next-generation sequencing (NGS) data to reveal the underlying clonal structure of tumors.

The tool proposes a generative model for NGS data obtained from multiple subsections of a single tumor. Clomial estimates the genotypes and relative frequencies of the tumor's clonal populations through an expectation-maximization procedure. The validity of Clomial's approach is demonstrated through simulations and further applied to real-world scenarios, including the analysis of primary breast cancer and its metastatic lymph node. By subdividing the tumor, performing exome sequencing on each subsection, and conducting deep sequencing to count alleles, Clomial quantifies the frequencies of somatic variants to predict clonal relationships that align with both phylogenetic and spatial data.