The trans-omics landscape of COVID-19

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Abstract

The outbreak of coronavirus disease 2019 (COVID-19) is a global health emergency. Various omics results have been reported for COVID-19, but the molecular hallmarks of COVID-19, especially in those patients without comorbidities, have not been fully investigated. Here we collect blood samples from 231 COVID-19 patients, prefiltered to exclude those with selected comorbidities, yet with symptoms ranging from asymptomatic to critically ill. Using integrative analysis of genomic, transcriptomic, proteomic, metabolomic and lipidomic profiles, we report a trans-omics landscape for COVID-19. Our analyses find neutrophils heterogeneity between asymptomatic and critically ill patients. Meanwhile, neutrophils over-activation, arginine depletion and tryptophan metabolites accumulation correlate with T cell dysfunction in critical patients. Our multi-omics data and characterization of peripheral blood from COVID-19 patients may thus help provide clues regarding pathophysiology of and potential therapeutic strategies for COVID-19.

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  1. SciScore for 10.1101/2020.07.17.20155150: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Ethics Statement: This study was reviewed and approved by the Institutional Review Board of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (TJ-IRB20200405).
    Consent: All the enrolled patients signed an informed consent form, and all the blood samples were collected using the rest of the standard diagnostic tests, with no burden to the patients.
    RandomizationSequencing Library Construction and Data Generation: The whole genome data was generated through the following steps: 1) DNA was randomly fragmented by Covaris.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableThe mean age of the patients was 46.7 years old (Standard Deviation=13.5), and the ratio of male to female was 1.12:1.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Sequencing Library Construction and Data Generation: The whole genome data was generated through the following steps: 1) DNA was randomly fragmented by Covaris.
    Covaris
    suggested: None
    Sequencing reads were mapped to hg38 reference genome using BWA algorithm (Li and Durbin, 2009).
    BWA
    suggested: (BWA, RRID:SCR_010910)
    Variant Quality Score Recalibration was performed using Genome Analysis Toolkit (GATK version 4.1.2)
    Genome Analysis Toolkit
    suggested: None
    GATK
    suggested: (GATK, RRID:SCR_001876)
    Genotype-Phenotype Association Analysis: PCA was performed using PLINK (v1.9) (Chang et al., 2015).
    PLINK
    suggested: (PLINK, RRID:SCR_001757)
    Gene Expression Analysis: RNA-seq raw sequencing reads were filtered by SOAPnuke (Li et al., 2008) to remove reads with sequencing adapter, with low-quality base ratio (base quality < 5) > 20%, and with unknown base (’N’ base) ratio > 5%
    SOAPnuke
    suggested: (SOAPnuke, RRID:SCR_015025)
    After data filtering, the clean reads were mapped to the reference genome and other sRNA database including miRbase
    miRbase
    suggested: (miRBase, RRID:SCR_017497)
    siRNA, piRNA and snoRNA using Bowtie2 (Langmead and Salzberg, 2012).
    Bowtie2
    suggested: (Bowtie 2, RRID:SCR_016368)
    Particularly, cmsearch (Nawrocki and Eddy, 2013) was performed for Rfam mapping.
    Rfam
    suggested: (Rfam, RRID:SCR_007891)
    Differential expression analysis was performed using DESeq2 (v1.4.5) (Love et al., 2014) with gender and age as confounders to control for the additional variation and the detection cutoff was set as adjusted P < 0.05 and log2 of fold change ≥ 1.
    DESeq2
    suggested: (DESeq, RRID:SCR_000154)
    , gene ontology (GO) enrichment analysis were performed to obtain the enriched GO Biological Process terms of proteins in different clusters by clusterProfiler (Yu et al., 2012).
    GO Biological
    suggested: None
    clusterProfiler
    suggested: (clusterProfiler, RRID:SCR_016884)
    And the 7 lists of metabolites in KEGG ID were classified into pathways by the Kyoto encyclopedia of genes and genomes (KEGG) database.
    KEGG
    suggested: (KEGG, RRID:SCR_012773)
    Correlation Network Analysis: Pairwise Spearman’s rank correlations were calculated using the r package ‘Hmisc’ and weighted, undirected networks were plotted with Cytoscape.
    Cytoscape
    suggested: (Cytoscape, RRID:SCR_003032)
    Data Preprocessing for Machine Learning: Extreme gradient boosting (XGBoost) (Chen and Guestrin, 2016), an ensemble algorithm of decision trees, was developed to predict patient severity status based on multi-omics data of mRNA transcripts (n=13323, mRNAs with FPKM >1 in at least one sample were retained), proteins (n=634), metabolites (n=814), lipids (n=742) from 135 patients (asymptomatic n=53, mild n=39, severe n=27, and critical n=16)using the open-sourced Python package (https://xgboost.readthedocs.io/en/latest/, version=1.0.0).
    Python
    suggested: (IPython, RRID:SCR_001658)

    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: Please consider improving the rainbow (“jet”) colormap(s) used on page 41. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.


    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.

    About SciScore

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