A Common Methodological Phylogenomics Framework for intra-patient heteroplasmies to infer SARS-CoV-2 sublineages and tumor clones

We present a common methodological framework to infer the phylogenomics from genomic data, be it reads of SARS-CoV-2 of multiple COVID-19 patients or bulk DNAseq of the tumor of a cancer patient. The commonality is in the phylogenetic retrodiction based on the genomic reads in both scenarios. While there is evidence of heteroplasmy, i.e., multiple lineages of SARS-CoV-2 in the same COVID-19 patient; to date, there is no evidence of sublineages recombining within the same patient. The heterogeneity in a patient’s tumor is analogous to intra-patient heteroplasmy and the absence of recombination in the cells of tumor is a widely accepted assumption. Just as the different frequencies of the genomic variants in a tumor presupposes the existence of multiple tumor clones and provides a handle to computationally infer them, we postulate that so do the different variant frequencies in the viral reads, offering the means to infer the multiple co-infecting sublineages. We describe the Concerti computational framework for inferring phylogenies in each of the two scenarios. To demonstrate the accuracy of the method, we reproduce some known results in both scenarios. We also make some additional discoveries. We uncovered new potential parallel mutation in the evolution of the SARS-CoV-2 virus. In the context of cancer, we uncovered new clones harboring resistant mutations to therapy from clinically plausible phylogenetic tree in a patient.