02553nas a2200301 4500008004100000022001400041245009700055210006900152260001500221490000700236520154600243653001801789653001401807653001501821653002801836100002501864700002001889700003301909700001801942700002901960700002401989700002302013700002002036700002202056700002602078700002002104856012702124 2021 eng d a2047-217X00aHighly accurate whole-genome imputation of SARS-CoV-2 from partial or low-quality sequences.0 aHighly accurate wholegenome imputation of SARSCoV2 from partial  c2021 12 020 v103 a

BACKGROUND: The current SARS-CoV-2 pandemic has emphasized the utility of viral whole-genome sequencing in the surveillance and control of the pathogen. An unprecedented ongoing global initiative is producing hundreds of thousands of sequences worldwide. However, the complex circumstances in which viruses are sequenced, along with the demand of urgent results, causes a high rate of incomplete and, therefore, useless sequences. Viral sequences evolve in the context of a complex phylogeny and different positions along the genome are in linkage disequilibrium. Therefore, an imputation method would be able to predict missing positions from the available sequencing data.

RESULTS: We have developed the impuSARS application, which takes advantage of the enormous number of SARS-CoV-2 genomes available, using a reference panel containing 239,301 sequences, to produce missing data imputation in viral genomes. ImpuSARS was tested in a wide range of conditions (continuous fragments, amplicons or sparse individual positions missing), showing great fidelity when reconstructing the original sequences, recovering the lineage with a 100% precision for almost all the lineages, even in very poorly covered genomes (<20%).

CONCLUSIONS: Imputation can improve the pace of SARS-CoV-2 sequencing production by recovering many incomplete or low-quality sequences that would be otherwise discarded. ImpuSARS can be incorporated in any primary data processing pipeline for SARS-CoV-2 whole-genome sequencing.

10aGenome, Viral10aPhylogeny10aSARS-CoV-210aWhole Genome Sequencing1 aOrtuno, Francisco, M1 aLoucera, Carlos1 aCasimiro-Soriguer, Carlos, S1 aLepe, Jose, A1 aMartinez, Pedro, Camacho1 aDiaz, Laura, Merino1 ade Salazar, Adolfo1 aChueca, Natalia1 aGarcĂ­a, Federico1 aPerez-Florido, Javier1 aDopazo, Joaquin uhttps://www.clinbioinfosspa.es/content/highly-accurate-whole-genome-imputation-sars-cov-2-partial-or-low-quality-sequences