Children’s Hospital Los Angeles COVID-19 Analysis Research Database (CARD) - A Resource for Rapid SARS-CoV-2 Genome Identification Using Interactive Online Phylogenetic Tools

Abstract

Effective response to the Coronavirus Disease 2019 (COVID-19) pandemic requires genomic resources and bioinformatics tools for genomic epidemiology and surveillance studies that involve characterizing full-length viral genomes, identifying origins of infections, determining the relatedness of viral infections, performing phylogenetic analyses, and monitoring the continuous evolution of the SARS-CoV-2 viral genomes. The Children's Hospital, Los Angeles (CHLA) COVID-19 Analysis Research Database (CARD) (https://covid19.cpmbiodev.net/) is a comprehensive genomic resource that provides access to full-length SARS-CoV-2 viral genomes and associated meta-data for over 30,000 (as of May 20, 2020) isolates collected from global sequencing repositories and the sequencing performed at the Center for Personalized Medicine (CPM) at CHLA. Reference phylogenetic trees of global and USA viral isolates were constructed and are periodically updated using selected high quality SARS-CoV-2 genome sequences. These provide the baseline and analytical context for identifying the origin of a viral infection, as well as the relatedness of SARS-CoV-2 genomes of interest. A web-based and interactive Phylogenetic Tree Browser supports flexible tree manipulation and advanced analysis based on keyword search while highlighting time series animation, as well as subtree export for graphical representation or offline exploration. A Virus Genome Tracker accepts complete or partial SARS-CoV-2 genome sequence, compares it against all available sequences in the database (>30,000 at time of writing), detects and annotates the variants, and places the new viral isolate within the global or USA phylogenetic contexts based upon variant profiles and haplotype comparisons, in a few seconds. The generated analysis can potentially aid in genomic surveillance to trace the transmission of any new infection. Using CHLA CARD, we demonstrate the identification of a candidate outbreak point where 13 of 31 CHLA internal isolates may have originated. We also discovered multiple indels of unknown clinical significance in the orf3a gene, and revealed a number of USA-specific variants and haplotypes.

Comprehensive Genome Analysis of 6,000 USA SARS-CoV-2 Isolates Reveals Haplotype Signatures and Localized Transmission Patterns by State and by Country

“…The major external resources of SARS-CoV-2 strains, genome sequences, and variants were GISAID, GenBank, CNCB, and NextStrain. Details about how the sequences were collected and further processed in CHLA COVID-19 Analysis Research Database (CARD) were described previously (Shen et al, 2020b).…”

“…The rapid accumulation and sharing of SARS-CoV-2 genome sequences at an unprecedented speed have greatly facilitated haplotype-based genomic epidemiology studies. Since the first SARS-CoV-2 genome sequence was reported in January of 2020, as of May 20th 2020, there have been over 30,000 sequences deposited to GISAID (Elbe and Buckland-Merrett, 2017;Shu and McCauley, 2017), 1 NCBI Virus, 2 the China National Center for Bioinformation (CNCB) 2019 nCoV Resource (Zhao et al, 2020) 3 and other data repositories (Shen et al, 2020b).…”

“…Country-, state-and possibly city-specific variant profiles may contribute to varied disease exemplifications and fatality rates observed across the globe along with host factors such as age, ethnicity and comorbidity. In our previous study, we established a comprehensive COVID-19 genomic resource, Children's Hospital Los Angeles (CHLA) COVID-19 Analysis Research Database (CARD), by harmonizing data from GISAID, NCBI Virus, CNCB and other resources (Shen et al, 2020b). Leveraging this extensive resource, in this study, we performed a comprehensive study of all publicly available SARS-CoV-2 genome sequences at the time of study, restricted to comparisons of global vs. USA isolates, which included 83 isolated that we sequenced at the Children's Hospital Los Angeles (Shen et al, 2020b).…”

“…In our previous study, we established a comprehensive COVID-19 genomic resource, Children's Hospital Los Angeles (CHLA) COVID-19 Analysis Research Database (CARD), by harmonizing data from GISAID, NCBI Virus, CNCB and other resources (Shen et al, 2020b). Leveraging this extensive resource, in this study, we performed a comprehensive study of all publicly available SARS-CoV-2 genome sequences at the time of study, restricted to comparisons of global vs. USA isolates, which included 83 isolated that we sequenced at the Children's Hospital Los Angeles (Shen et al, 2020b). We called variants from each genome sequence, and performed categorical analyses of variants and haplotypes as stratified by the geographic locations.…”

ViruSurf: an integrated database to investigate viral sequences

“…Although the origin sources provide well-organized data portals (NCBI Virus (11), the COVID-19 Data Portal https://www.covid19dataportal.org/, and GISAID EpiCoV data browser), these do not allow for an integrated search over multiple sources, nor they provide fast selection using sequence variants. A number of other integrated interfaces are being developed in alternative research contexts: UCSC SARS-CoV-2 Genome Browser (9); 2019nCoVR (24) at the Chinese National Genomics Data Center; VirusDIP (22) at the China National GeneBank; CovSeq (13); CARD (18). Compared to other resources, ViruSurf has much stronger query and search capabilities; we use the power of conceptual modeling to structure metadata and to organize data integration and curation; we support search queries allowing to combine filters on metadata, nucleotide and amino acid mutations in an effective and scalable way, treating all of them as first-class citizens.…”