Deconvoluting complex correlates of COVID-19 severity with a multi-omic pandemic tracking strategy

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1. Version published to 10.1038/s41467-022-32397-8

   Aug 30, 2022
2. 

   ScreenIT

   Aug 19, 2021

   SciScore for 10.1101/2021.08.04.21261547: (What is this?)

   Please note, not all rigor criteria are appropriate for all manuscripts.

   Table 1: Rigor

   Ethics	not detected.
   Sex as a biological variable	not detected.
   Randomization	Briefly, 3 ul of total nucleic acid was used as input for a randomly primed cDNA synthesis reaction.
   Blinding	not detected.
   Power Analysis	not detected.

   Table 2: Resources

   Software and Algorithms
   Sentences	Resources
   Sample Collection and diagnostics: Residual VTM from SARS-CoV-2 positive nasopharyngeal swabs collected during clinical assessment of asymptomatic and symptomatic patients at Stanford Healthcare were used in accordance with the Stanford School of Medicine Institutional Review	Stanford Healthcare suggested: None
   Clinical data were obtained through the STAnford Research Repository (STARR), a Stanford Medicine’s approved …

   SciScore for 10.1101/2021.08.04.21261547: (What is this?)

   Please note, not all rigor criteria are appropriate for all manuscripts.

   Table 1: Rigor

   Ethics	not detected.
   Sex as a biological variable	not detected.
   Randomization	Briefly, 3 ul of total nucleic acid was used as input for a randomly primed cDNA synthesis reaction.
   Blinding	not detected.
   Power Analysis	not detected.

   Table 2: Resources

   Software and Algorithms
   Sentences	Resources
   Sample Collection and diagnostics: Residual VTM from SARS-CoV-2 positive nasopharyngeal swabs collected during clinical assessment of asymptomatic and symptomatic patients at Stanford Healthcare were used in accordance with the Stanford School of Medicine Institutional Review	Stanford Healthcare suggested: None
   Clinical data were obtained through the STAnford Research Repository (STARR), a Stanford Medicine’s approved resource for working with clinical data for research purposes extracted from the Epic database management system used by the Stanford hospitals.	STAnford suggested: (Stanford CNI, RRID:SCR_014529) STARR suggested: (Starr, RRID:SCR_001071)
   Viral and Metagenomic Genome Alignment: For SARS-CoV-2 genomes, FASTQ sequences were aligned to the SARS-CoV-2 reference genome NC_045512.2 using minimap2.36 Non-SARS-CoV-2 reads were filtered out with Kraken2,37 using an index of human and viral genomes in RefSeq (index downloaded from https://genexa.ch/sars2-bioinformatics-resources/).	RefSeq suggested: (RefSeq, RRID:SCR_003496)
   Host and metagenomic RNA alignment was performed using STAR run against a combined index of the human reference genome grch38, SARS-CoV2 (SARSCoV2_NC_045512.2), and ERCC spike-ins.	STAR suggested: (STAR, RRID:SCR_004463)
   Host Genome Sequence Alignment: Low-coverage FASTQ sequences underwent quality control assessment via FastQC v0.11.8 before alt-aware alignment to GRCh38.p12 using BWA-MEM v0.7.17-r1188.	FastQC suggested: (FastQC, RRID:SCR_014583) BWA-MEM suggested: (Sniffles, RRID:SCR_017619)
   After duplicate marking, base quality score recalibration was performed with Picard Tools’ BaseRecalibrator and high-confidence variant call sets from dbSNP and the 1000 Genomes Project.	Picard suggested: (Picard, RRID:SCR_006525) dbSNP suggested: (dbSNP, RRID:SCR_002338) 1000 Genomes Project suggested: (1000 Genomes Project and AWS, RRID:SCR_008801)
   Quality control metrics, including coverage, were generated with Qualimap BAMQC v2.2.1, Samtools v1.10, and Mosdepth v0.2.9.	Qualimap suggested: (QualiMap, RRID:SCR_001209) Samtools suggested: (SAMTOOLS, RRID:SCR_002105)
   Finally, quality control reports for each sample were aggregated using MultiQC v1.9	MultiQC suggested: (MultiQC, RRID:SCR_014982)
   Reproducible code and steps are available at Protocols.io doi: (https://www.protocols.io/private/8CFBD1AD8FE611EA815E0A58A9FEAC2A) All high confidence calls were contributed to the COVID19 Host Genetics Initiative.3 Variant Calling, Imputation, PCA, Kinshiship: BAM files were used for an initial calling with bcftools v1.9 mpileup.	bcftools suggested: (SAMtools/BCFtools, RRID:SCR_005227)
   500 µl of 1.3 pM DNA sequencing library was loaded into a MiniSeq Mid Output Kit (300-cycles) (FC-420-1004), and sequenced using MiniSeq DNA sequencer (Illumina Inc., San Diego, CA).	MiniSeq suggested: None
   When self-reported ethnicity was not available, genetic ancestry calculated from the low pass WGS in this study was used as described above.	WGS suggested: None
   HLA serotype and allele frequencies were calculated in both Mild and Severe groups, and Odd Ratio (OR:	Mild suggested: (MILD, RRID:SCR_003335)
   We assumed the HKY mutation model 57 with default hyperparameter priors in the BEAST2 software 58.	BEAST2 suggested: (BEAST2, RRID:SCR_017307)

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   Results from OddPub: Thank you for sharing your code.

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   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.

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   Results from TrialIdentifier: No clinical trial numbers were referenced.

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   Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

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   Results from JetFighter: We did not find any issues relating to colormaps.

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   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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   Results from scite Reference Check: We found no unreliable references.

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3. 

   Version published to 10.1101/2021.08.04.21261547v1 on medRxiv

   Aug 8, 2021