SARS-CoV-2 within-host diversity and transmission
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Abstract
A year into the severe acute respiratory syndrome coronavirus 2 pandemic, we are experiencing waves of new variants emerging. Some of these variants have worrying functional implications, such as increased transmissibility or antibody treatment escape. Lythgoe et al. have undertaken in-depth sequencing of more than 1000 hospital patients' isolates to find out how the virus is mutating within individuals. Overall, there seem to be consistent and reproducible patterns of within-host virus diversity. The authors observed only one or two variants in most samples, but a few carried many variants. Although the evidence indicates strong purifying selection, including in the spike protein responsible for viral entry, the authors also saw evidence for transmission clusters associated with households and other possible superspreader events. After transmission, most variants fizzled out, but occasionally some initiated ongoing transmission and wider dissemination.
Science , this issue p. eabg0821
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SciScore for 10.1101/2020.05.28.118992: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Software and Algorithms Sentences Resources Bioinformatics processing: De-multiplexed sequence read pairs were classified by Kraken v2 (39) using a custom database containing the human genome (GRCh38 build) and the full RefSeq set of bacterial and viral genomes (pulled May 2020) Krakensuggested: (Kraken, RRID:SCR_005484)Remaining reads, comprised of viral and unclassified reads, were trimmed in two stages: first to remove the random hexamer primers from the forward read and SMARTer TSO from the reverse read, and then to remove Illumina adapter sequences using Trimmomatic v0.36(40), with the ILLUMINACLIP options set to “2:10:7:1:true … SciScore for 10.1101/2020.05.28.118992: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Software and Algorithms Sentences Resources Bioinformatics processing: De-multiplexed sequence read pairs were classified by Kraken v2 (39) using a custom database containing the human genome (GRCh38 build) and the full RefSeq set of bacterial and viral genomes (pulled May 2020) Krakensuggested: (Kraken, RRID:SCR_005484)Remaining reads, comprised of viral and unclassified reads, were trimmed in two stages: first to remove the random hexamer primers from the forward read and SMARTer TSO from the reverse read, and then to remove Illumina adapter sequences using Trimmomatic v0.36(40), with the ILLUMINACLIP options set to “2:10:7:1:true MINLEN:80”. Trimmomaticsuggested: (Trimmomatic, RRID:SCR_011848)Trimmed reads were mapped to the SARS-CoV-2 RefSeq genome of isolate Wuhan-Hu-1 (NC_045512.2), using shiver (41) v1.5.7, with either smalt(42) or bowtie2 (43) as the mapper. bowtie2suggested: (Bowtie 2, RRID:SCR_016368)The resulting set, along with the reference genome Wuhan-Hu-1 (RefSeq ID NC_045512), were aligned using MAFFT (46), with some manual improvement of the algorithmic alignment and removal of problematic sequences performed as a post-processing step. RefSeqsuggested: (RefSeq, RRID:SCR_003496)MAFFTsuggested: (MAFFT, RRID:SCR_011811)Phylogenetic association of iSNVs and SNPs: Where an iSNV corresponded to a consensus SNP (by the base pair involved, not simply the site), we performed ancestral state reconstruction on the consensus trees using ClonalFrameML (48) to identify all branches upon which that substitution was involved. ClonalFrameMLsuggested: (Clonalframe, RRID:SCR_016060)Results from OddPub: Thank you for sharing your data.
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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