A behind-the-scenes tour of the IEDB curation process: an optimized process empirically integrating automation and human curation efforts.

The Immune Epitope Database and Analysis Resource (IEDB) provides the scientific community with open access to epitope data, as well as epitope prediction and analysis tools. The IEDB houses the most extensive collection of experimentally validated B-cell and T-cell epitope data, sourced primarily from published literature by expert curation. The data procurement requires systematic identification, categorization, curation and quality-checking processes. Here, we provide insights into these processes, with particular focus on the dividends they have paid in terms of attaining project milestones, as well as how objective analyses of our processes have identified opportunities for process optimization. These experiences are shared as a case study of the benefits of process implementation and review in biomedical big data, as well as to encourage idea-sharing among players in this ever-growing space.

The Immune Epitope Database and Analysis Resource Program 2003-2018: reflections and outlook.

The Immune Epitope Database and Analysis Resource (IEDB) contains information related to antibodies and T cells across an expansive scope of research fields (infectious diseases, allergy, autoimmunity, and transplantation). Capture and representation of the data to reflect growing scientific standards and techniques have required continual refinement of our rigorous curation and query and reporting processes beginning with the automated classification of over 28 million PubMed abstracts, and resulting in easily searchable data from over 20,000 published manuscripts. Data related to MHC binding and elution, nonpeptidics, natural processing, receptors, and 3D structure is first captured through manual curation and subsequently maintained through recuration to reflect evolving scientific standards. Upon promotion to the free, public database, users can query and export records of specific relevance via the online web portal which undergoes iterative development to best enable efficient data access. In parallel, the companion Analysis Resource site hosts a variety of tools that assist in the bioinformatic analyses of epitopes and related structures, which can be applied to IEDB-derived and independent datasets alike. Available tools are classified into two categories: analysis and prediction. Analysis tools include epitope clustering, sequence conservancy, and more, while prediction tools cover T and B cell epitope binding, immunogenicity, and TCR/BCR structures. In addition to these tools, benchmarking servers which allow for unbiased performance comparison are also offered. In order to expand and support the user-base of both the database and Analysis Resource, the research team actively engages in community outreach through publication of ongoing work, conference attendance and presentations, hosting of user workshops, and the provision of online help. This review provides a description of the IEDB database infrastructure, curation and recuration processes, query and reporting capabilities, the Analysis Resource, and our Community Outreach efforts, including assessment of the impact of the IEDB across the research community.

A survey of known immune epitopes in the enteroviruses strains associated with acute flaccid myelitis.

Enteroviruses are potentially linked to the emergence of Acute Flaccid Myelitis (AFM), a rare but very serious condition that affects the nervous system. AFM has been associated with coxsackievirus A16, enterovirus A71 (EVA71) and enterovirus D68 (EVD68). Little is known about host-pathogen interactions for these viruses, and whether immune responses may have a protective or immunopathological role in disease presentations. Towards addressing this issue, we used the Immune Epitope Database to assess the known inventory of B and T cell epitopes from enteroviruses, focusing on data related to human hosts. The extent of conservation in areas that are targets of B and T cell immune responses were examined. This analysis sheds light on regions of the enterovirus polypeptide that can be probed to induce a specific or cross-reactive B or T cell the immune response to enteroviruses, with a particular focus on coxsackievirus A16, EVA71 and EVD68. In addition, these analyses reveal the current gap-of-knowledge in the T and B cell immune responses that future studies should aim to address.

The Immune Epitope Database (IEDB): 2018 update.

The Immune Epitope Database (IEDB, iedb.org) captures experimental data confined in figures, text and tables of the scientific literature, making it freely available and easily searchable to the public. The scope of the IEDB extends across immune epitope data related to all species studied and includes antibody, T cell, and MHC binding contexts associated with infectious, allergic, autoimmune, and transplant related diseases. Having been publicly accessible for >10 years, the recent focus of the IEDB has been improved query and reporting functionality to meet the needs of our users to access and summarize data that continues to grow in quantity and complexity. Here we present an update on our current efforts and future goals.

Prior Dengue Virus Exposure Shapes T Cell Immunity to Zika Virus in Humans.

While progress has been made in characterizing humoral immunity to Zika virus (ZIKV) in humans, little is known regarding the corresponding T cell responses to ZIKV. Here, we investigate the kinetics and viral epitopes targeted by T cells responding to ZIKV and address the critical question of whether preexisting dengue virus (DENV) T cell immunity modulates these responses. We find that memory T cell responses elicited by prior infection with DENV or vaccination with tetravalent dengue attenuated vaccines (TDLAV) recognize ZIKV-derived peptides. This cross-reactivity is explained by the sequence similarity of the two viruses, as the ZIKV peptides recognized by DENV-elicited memory T cells are identical or highly conserved in DENV and ZIKV. DENV exposure prior to ZIKV infection also influences the timing and magnitude of the T cell response. ZIKV-reactive T cells in the acute phase of infection are detected earlier and in greater magnitude in DENV-immune patients. Conversely, the frequency of ZIKV-reactive T cells continues to rise in the convalescent phase in DENV-naive donors but declines in DENV-preexposed donors, compatible with more efficient control of ZIKV replication and/or clearance of ZIKV antigen. The quality of responses is also influenced by previous DENV exposure, and ZIKV-specific CD8 T cells from DENV-preexposed donors selectively upregulated granzyme B and PD1, unlike DENV-naive donors. Finally, we discovered that ZIKV structural proteins (E, prM, and C) are major targets of both the CD4 and CD8 T cell responses, whereas DENV T cell epitopes are found primarily in nonstructural proteins.IMPORTANCE The issue of potential ZIKV and DENV cross-reactivity and how preexisting DENV T cell immunity modulates Zika T cell responses is of great relevance, as the two viruses often cocirculate and Zika virus has been spreading in geographical regions where DENV is endemic or hyperendemic. Our data show that memory T cell responses elicited by prior infection with DENV recognize ZIKV-derived peptides and that DENV exposure prior to ZIKV infection influences the timing, magnitude, and quality of the T cell response. Additionally, we show that ZIKV-specific responses target different proteins than DENV-specific responses, pointing toward important implications for vaccine design against this global threat.