CoV2K model, a comprehensive representation of SARS-CoV-2 knowledge and data interplay.

Since the outbreak of the COVID-19 pandemic, many research organizations have studied the genome of the SARS-CoV-2 virus; a body of public resources have been published for monitoring its evolution. While we experience an unprecedented richness of information in this domain, we also ascertained the presence of several information quality issues. We hereby propose CoV2K, an abstract model for explaining SARS-CoV-2-related concepts and interactions, focusing on viral mutations, their co-occurrence within variants, and their effects. CoV2K provides a clear and concise route map for understanding different connected types of information related to the virus; it thus drives a process of data and knowledge integration that aggregates information from several current resources, harmonizing their content and overcoming incompleteness and inconsistency issues. CoV2K is available for exploration as a graph that can be queried through a RESTful API addressing single entities or paths through their relationships. Practical use cases demonstrate its application to current knowledge inquiries.

High Performance Integration Pipeline for Viral and Epitope Sequences.

With the spread of COVID-19, sequencing laboratories started to share hundreds of sequences daily. However, the lack of a commonly agreed standard across deposition databases hindered the exploration and study of all the viral sequences collected worldwide in a practical and homogeneous way. During the first months of the pandemic, we developed an automatic procedure to collect, transform, and integrate viral sequences of SARS-CoV-2, MERS, SARS-CoV, Ebola, and Dengue from four major database institutions (NCBI, COG-UK, GISAID, and NMDC). This data pipeline allowed the creation of the data exploration interfaces VirusViz and EpiSurf, as well as ViruSurf, one of the largest databases of integrated viral sequences. Almost two years after the first release of the repository, the original pipeline underwent a thorough refinement process and became more efficient, scalable, and general (currently, it also includes epitopes from the IEDB). Thanks to these improvements, we constantly update and expand our integrated repository, encompassing about 9.1 million SARS-CoV-2 sequences at present (March 2022). This pipeline made it possible to design and develop fundamental resources for any researcher interested in understanding the biological mechanisms behind the viral infection. In addition, it plays a crucial role in many analytic and visualization tools, such as ViruSurf, EpiSurf, VirusViz, and VirusLab.

EpiSurf: metadata-driven search server for analyzing amino acid changes within epitopes of SARS-CoV-2 and other viral species.

EpiSurf is a Web application for selecting viral populations of interest and then analyzing how their amino acid changes are distributed along epitopes. Viral sequences are searched within ViruSurf, which stores curated metadata and amino acid changes imported from the most widely used deposition sources for viral databases (GenBank, COVID-19 Genomics UK (COG-UK) and Global initiative on sharing all influenza data (GISAID)). Epitopes are searched within the open source Immune Epitope Database or directly proposed by users by indicating their start and stop positions in the context of a given viral protein. Amino acid changes of selected populations are joined with epitopes of interest; a result table summarizes, for each epitope, statistics about the overlapping amino acid changes and about the sequences carrying such alterations. The results may also be inspected by the VirusViz Web application; epitope regions are highlighted within the given viral protein, and changes can be comparatively inspected. For sequences mutated within the epitope, we also offer a complete view of the distribution of amino acid changes, optionally grouped by the location, collection date or lineage. Thanks to these functionalities, EpiSurf supports the user-friendly testing of epitope conservancy within selected populations of interest, which can be of utmost relevance for designing vaccines, drugs or serological assays. EpiSurf is available at two endpoints. Database URL: http://gmql.eu/episurf/ (for searching GenBank and COG-UK sequences) and http://gmql.eu/episurf_gisaid/ (for GISAID sequences).

VirusViz: comparative analysis and effective visualization of viral nucleotide and amino acid variants.

Variant visualization plays an important role in supporting the viral evolution analysis, extremely valuable during the COVID-19 pandemic. VirusViz is a web-based application for comparing variants of selected viral populations and their sub-populations; it is primarily focused on SARS-CoV-2 variants, although the tool also supports other viral species (SARS-CoV, MERS-CoV, Dengue, Ebola). As input, VirusViz imports results of queries extracting variants and metadata from the large database ViruSurf, which integrates information about most SARS-CoV-2 sequences publicly deposited worldwide. Moreover, VirusViz accepts sequences of new viral populations as multi-FASTA files plus corresponding metadata in CSV format; a bioinformatic pipeline builds a suitable input for VirusViz by extracting the nucleotide and amino acid variants. Pages of VirusViz provide metadata summarization, variant descriptions, and variant visualization with rich options for zooming, highlighting variants or regions of interest, and switching from nucleotides to amino acids; sequences can be grouped, groups can be comparatively analyzed. For SARS-CoV-2, we manually collect mutations with known or predicted levels of severity/virulence, as indicated in linked research articles; such critical mutations are reported when observed in sequences. The system includes light-weight project management for downloading, resuming, and merging data analysis sessions. VirusViz is freely available at http://gmql.eu/virusviz/.

ViruSurf: an integrated database to investigate viral sequences.

ViruSurf, available at http://gmql.eu/virusurf/, is a large public database of viral sequences and integrated and curated metadata from heterogeneous sources (RefSeq, GenBank, COG-UK and NMDC); it also exposes computed nucleotide and amino acid variants, called from original sequences. A GISAID-specific ViruSurf database, available at http://gmql.eu/virusurf_gisaid/, offers a subset of these functionalities. Given the current pandemic outbreak, SARS-CoV-2 data are collected from the four sources; but ViruSurf contains other virus species harmful to humans, including SARS-CoV, MERS-CoV, Ebola and Dengue. The database is centered on sequences, described from their biological, technological and organizational dimensions. In addition, the analytical dimension characterizes the sequence in terms of its annotations and variants. The web interface enables expressing complex search queries in a simple way; arbitrary search queries can freely combine conditions on attributes from the four dimensions, extracting the resulting sequences. Several example queries on the database confirm and possibly improve results from recent research papers; results can be recomputed over time and upon selected populations. Effective search over large and curated sequence data may enable faster responses to future threats that could arise from new viruses.