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Comment
. 2022 Aug 23;119(34):e2205269119.
doi: 10.1073/pnas.2205269119. Epub 2022 Aug 1.

Data analysis of viral complementary DNA/RNA sequences for low-frequency intrahost-single nucleotide variants in COVID-19

Samarth Chandra  1
Affiliations
Comment

Data analysis of viral complementary DNA/RNA sequences for low-frequency intrahost-single nucleotide variants in COVID-19

Samarth Chandra. Proc Natl Acad Sci U S A. .
No abstract available

PubMed Disclaimer

Conflict of interest statement

Competing interest statement: S.C. holds shares in Spinor Research Labs Private Limited.

Figures

Fig. 1.
Fig. 1.
The number of iSNVs detected with different dilutions and frequencies. (A) High-depth samples from nasopharyngeal swabs of COVID-19 patients were down sampled, and the number of iSNVs identified above the 3% minor allele frequency (MAF) threshold is plotted for different dilutions. Different curves represent different samples. Bashor et al. (1) do not specify their frequency threshold, but even a different threshold is likely to give similar curves. (Figure 1A of ref. has a plot of the number of iSNVs found in lower titer samples without dilution.) Reproduced with permission from ref. . (B) MAF is plotted for two replicates against each other for high-depth samples from nasopharyngeal swabs of COVID-19 patients. For concordant pairs, the data points are expected to be along the 45° line, while for discordant pairs, they are expected to be on one of the axes. Clearly, below an MAF of 3%, the data are nearly the same as noise. (Figure S8 of ref. shows the necessity of a threshold of around 3% at high titers.) Also, that ref. and ref. use different primers should not matter for the broad trends. Reprinted with permission from ref. , which is licensed under CC BY 4.0.
Fig. 2.
Fig. 2.
Frequencies of true iSNVs (blue) and false iSNVs (red) at different genome locations in a sequencing experiment with controlled mixtures of RNA sequences of SARS-CoV-2 genomes and RNA sequences of variant-containing SARS-CoV-2 genomes (ref. has details of the experiment). Different subplots are for samples with different viral genome copies per microliter. At lower titers, false iSNVs are present at significantly higher frequency. (Extrapolating to Fig. 1B, for lower titers the noise region will expand significantly, requiring a threshold much higher than 3%.). Reprinted with permission from ref. , which is licensed under CC BY 4.0.
See this image and copyright information in PMC

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References

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