Mapping the Evolutionary Space of SARS-CoV-2 Variants to Anticipate Emergence of Subvariants Resistant to COVID-19 Therapeutics
Fig 6
The mutational profiles of new SARS-CoV-2 sublineages are predicted well by volatility patterns in their parental lineages.
(A) Sequences from the baselines of the indicated VOCs were used to calculate the combined probabilities for mutations at all spike positions. These values were compared with the absence or presence of a mutation that defines a Pango sublineage at the sites. The number of sublineage founder mutations (n) in each VOC and the AUC values are shown. (B) Mutation probabilities calculated using the sequences of each lineage (input) are compared with the sublineage mutational outcomes observed in all VOCs (outcome). The highest AUC for each lineage outcome is bolded. (C) Weblogos of the minority variants at sublineage mutation sites. Frequencies are expressed as a fraction of all sequences with a non-lineage ancestral residue. The residue change from the lineage ancestor is shown below the axis, and the emergent residue is also highlighted in red font. (D) Relationship between sampling of residues in the parental lineage and their emergence as the sublineage-defining mutations. The frequencies of all possible residues (excluding the VOC ancestral form) at the sites shown in panel C were calculated as a fraction of all minority variants identified in each VOC. The values were partitioned into the indicated bins. For example, position 138 in lineage B.1.1.7 contained the minority variants His, Tyr, Asn, Ala and Gly at 62.8, 32.7, 1.9, 1.3 and 1.3 percent, respectively, and no representation of all other residues–all 21 residue options (including N-linked glycosylation motifs and deletion events but excluding the majority variant) were distributed into their corresponding frequency bins. For each bin, we calculated the number of residues that emerged as the new sublineage-defining mutation (indicated in red font) as a percent of all instances in that bin (in black font).