TriTrypDB: An integrated functional genomics resource for kinetoplastida

Abstract

Parasitic diseases caused by kinetoplastid parasites are a burden to public health throughout tropical and subtropical regions of the world. TriTrypDB (https://tritrypdb.org) is a free online resource for data mining of genomic and functional data from these kinetoplastid parasites and is part of the VEuPathDB Bioinformatics Resource Center (https://veupathdb.org). As of release 59, TriTrypDB hosts 83 kinetoplastid genomes, nine of which, including Trypanosoma brucei brucei TREU927, Trypanosoma cruzi CL Brener and Leishmania major Friedlin, undergo manual curation by integrating information from scientific publications, high-throughput assays and user submitted comments. TriTrypDB also integrates transcriptomic, proteomic, epigenomic, population-level and isolate data, functional information from genome-wide RNAi knock-down and fluorescent tagging, and results from automated bioinformatics analysis pipelines. TriTrypDB offers a user-friendly web interface embedded with a genome browser, search strategy system and bioinformatics tools to support custom in silico experiments that leverage integrated data. A Galaxy workspace enables users to analyze their private data (e.g., RNA-sequencing, variant calling, etc.) and explore their results privately in the context of publicly available information in the database. The recent addition of an annotation platform based on Apollo enables users to provide both functional and structural changes that will appear as 'community annotations' immediately and, pending curatorial review, will be integrated into the official genome annotation.

Fig 1. Home page of TriTrypDB.

(A) Header on all site pages that includes site search, menu bar providing access to all searches, data and tools, and links for social media, registration, login and user profile. (B) The recently implemented ‘My Organism Preferences’ filter. (C) The left hand search panel contains searches of different data in the database, organized into categories. (D) The overview of resources and tools section provides vignettes to help users get started on specific tools and resources of interest. (E) The expandable news and tweets section (collapsed by default) offers quick access to news releases and recent tweets. (F) Links to more detailed step-by-step instructional material. (G) Footer consisting of hyperlinked logos to other VEuPathDB resources in addition to the Gitter Community Chat button.

Fig 2. Search strategies as in silico experiments and functional enrichment analysis.

(A) The graphic panel shows an example multi-step search strategy (https://tritrypdb.org/tritrypdb/app/workspace/strategies/import/9c17640460e66cd5). (B) Results of the first step of the search strategy, with the redesigned vertical organism filter on the left (red arrow) and the results table on right. (C) Redesigned ‘Add Step’ popup showing the three options to add steps, ‘Combine’, ‘Transform’ and ‘Genomic Colocation’, and the details of the chosen option. (D) The three options available for the analysis of gene results: GO enrichment, metabolic pathway enrichment and word cloud. (E) The form for selecting appropriate parameters for GO enrichment analysis.

Fig 3. Community curation via User Comments and Apollo.

(A) On the top of the gene record page are links to add User Comments and to access Apollo. (B) User Comment interface. (C) To annotate a gene in Apollo, the current gene model needs to be added to the User-created Annotations Area. (D) Interface in Apollo to add gene symbols, product descriptions, GO terms, database references and comments. Once the annotation is finalized, the status needs to be set as finished. (E) Finished annotations are shown on the gene page in the Gene models graphic in the track ‘Community annotations from Apollo’. (F) A popup shows Apollo product descriptions, evidence code and the publication that is associated with the gene. (G) Apollo product description, gene symbol and publication are shown in the Annotation, curation and identifiers section on the gene record page.