PMC:7519301 / 15334-17848 JSONTXT 8 Projects

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Id Subject Object Predicate Lexical cue
T101 0-275 Sentence denotes To test whether this site was under selection, we used likelihood-based, phylogenetically informed models that assume branch-specific substitution rates (29) and implemented a sampling strategy to circumvent computational limitations imposed by the large number of sequences.
T102 276-477 Sentence denotes Subsampled alignments (100 times at a 10% sampling fraction) had diversity estimates statistically similar to the complete alignment for each gene (Mann−Whitney U test, P > 0.09; SI Appendix, Fig. S3).
T103 478-906 Sentence denotes In S, only site 614 was estimated to be under diversifying selection in a majority of subsampled alignments (58%); evidence of diversifying selection indicates that genetic diversity increases in the viral population (i.e., there was a higher proportion of mutations causing an amino acid change than not at site 614, or, the nonsynonymous/synonymous substitution rates ratio, dN/dS, was over 1, P < 0.1) (SI Appendix, Fig. S4).
T104 907-1088 Sentence denotes Because diversifying selection is often associated with the host adaptive response, we considered whether the D614G mutation coincided with targets of antibody and T cell responses.
T105 1089-1220 Sentence denotes Site 614 is at the interface between the S1 and S2 subunits and is thus not highly accessible to antibodies (SI Appendix, Fig. S5).
T106 1221-1389 Sentence denotes Therefore, we predict that antibodies to the native S protein would cross-react with S containing the D614G mutation, in agreement with recent reports (24, 25, 27, 28).
T107 1390-1659 Sentence denotes Many known neutralizing antibodies target the RBD, yet we found little evidence that mutations could affect binding to the ACE2 receptor, as only five shared mutations were identified at contact sites with the ACE2 receptor, and all were found in 10 or fewer sequences.
T108 1660-1753 Sentence denotes Of these, one mutation, at position 489, was synonymous and found in three sequences (0.02%).
T109 1754-1887 Sentence denotes The others were nonsynonymous: G476S (n = 10 sequences, 0.05%), Y453F (n = 5, 0.02%), G446V (n = 3, 0.02%), and A475V (n = 2, 0.01%).
T110 1888-2210 Sentence denotes To predict the potential immune pressure linked to T cell responses, we developed a T cell immunogenicity index which takes into account the CD8 and CD4 epitope repertoires in the structural proteins of SARS-CoV-2 (S, N, M, E) and the frequency of human leukocyte antigen (HLA) alleles or haplotypes in a given population.
T111 2211-2375 Sentence denotes We found that sites with mutations, including 614 in S, were not colocalized with T cell epitopes frequently identified in different populations (SI Appendix, Figs.
T112 2376-2514 Sentence denotes S6 and S7), and there was no significant relationship between the number of mutations and the immunogenicity index (SI Appendix, Fig. S8).