CovidOutcome2: a tool for SARS-CoV2 mutation identification and for disease severity prediction

Our goal was to develop a platform, CovidOutcome2, capable of predicting disease severity from viral mutation profiles using automated machine learning (autoML) and deep neural networks applied to the available large corpus of sequenced SARS-CoV2 genomes. CovidOutcome2 accepts either user-submitted genomes or user defined mutation combinations as the input. The output is a predicted severity score plus a list of identified, annotated mutations and their functional effects in VCF format. The best model performance is a ROC-AUC 0.899 for the model including patient age and ROC-AUC 0.83 for the model without patient age. AvailabilityCovidOutcome is freely available online under the URL https://www.covidoutcome.bio-ml.com as well as in a standalone version https://github.com/bio-apps/covid-outcome.

COVIDOUTCOME - Estimating COVID Severity Based on Mutation Signatures in the SARS-CoV-2 Genome

IntroductionNumerous studies demonstrate frequent mutations in the genome of SARS-CoV-2. Our goal was to statistically link mutations to severe disease outcome. MethodsWe used an automated machine learning approach where 1,594 viral genomes with available clinical follow-up data were used as the training set (797 "severe" and 797 "mild"). The best algorithm, based on random forest classification combined with the LASSO feature selection algorithm was employed to the training set to link mutation signatures and outcome. The performance of the final model was estimated by repeated, stratified, 10-fold cross validation (CV), then adjusted for multiple testing with Bootstrap Bias Corrected CV. ResultsWe identified 26 protein and UTR mutations significantly linked to severe outcome. The best classification algorithm uses a mutation signature of 22 mutations as well as the patients age as the input and shows high classification efficiency with an AUC of 0.94 (CI: [0.912, 0.962]) and a prediction accuracy of 87% (CI: [0.830, 0.903]). Finally, we established an online platform (https://covidoutcome.com/) which is capable to use a viral sequence and the patients age as the input and provides a percentage estimation of disease severity. DiscussionWe demonstrate a statistical association between mutation signatures of SARS-CoV-2 and severe outcome of COVID-19. The established analysis platform enables a real-time analysis of new viral genomes. KEY MESSAGESO_LIA statistical link between SARS-Cov-2 mutation status and severe COVID outcome was established using automated machine learning techniques based on random forest and logistic regression combined with feature selection algorithms. C_LIO_LIA mutation signature based on 3,779 protein coding and 36 UTR mutations capable to identify severe outcome cases was established. C_LIO_LIThe trained model showed high classification performance (AUC=0.94 (CI: [0.912, 0.962]), accuracy=0.87 (CI: [0.830, 0.903])). C_LIO_LIA registration-free web-server for automated classification of new samples was set up and is accessible at http://www.covidoutcome.com. C_LIO_LIThe established pipeline provides a quick assessment of future patients warranting a prospective clinical validation. C_LI