PHDtools: A platform for pathogen detection and multi-dimensional genetic signatures decoding to realize pathogen...

Facing the emerging diseases, rapid identification of the pathogen and multi-dimensional characterization of the genomic features at both isolate-level and population-level through high-throughput sequencing data can provide invaluable information to guide the development of antiviral agents and strategies. However, a user-friendly program is in urgent need for clinical laboratories without bioinformatics background to decode the complex big genomics data.

In this study, we developed an interactive online platform named PHDtools with a total of 15 functions to analyze metagenomics data to identify the potential pathogen and decode multi-dimensional genetic signatures including intra-/inter-host variations and lineage-level variations. The platform was applied to analyze the meta-genomic data of the samples collected from the 172 imported COVID-19 cases.

According to the analytical results of mNGS, 27 patients were found to have the co-infections of SARS-CoV-2 with either influenza virus (n = 9) or human picobirnavirus (n = 19). Enough coverages of all the assembled SARS-CoV-2 genomes provided the sub-lineages of Omicron variant, and the number of mutations in the non-structural genes and M gene was increased, as well as the intra-host variations occurred in E and M gene were under positive selection (Ka/Ks > 1). These findings of increased or changed mutations in the SARS-CoV-2 genome characterized the current adaptive evolution patterns of Omicron sub-lineages, and revealed the evolution speed of these sub-lineages might increase.

Consequently, the application of PHDtools has proved that this platform is accurate, user-friendly and convenient for clinical users who are deficient in bioinformatics, and the clinical monitor of SARS-CoV-2 genomes by PHDtools also highlighted the potential evolution features of current SARS-CoV-2 and indicated that the development of anti-SARS-CoV-2 agents and new-designed vaccines should incorporate the gene variations other than S gene.