Ontology-based representation and analysis of conditional vaccine immune responses using Omics data.

ImmPort, the world's largest repository of immunology data, includes many vaccine immune response datasets. ImmPort maps the metadata of these studies to ontology and database schema. As of February 28, 2023, our ImmPort data analysis identified 6.258 immune exposures using 47 vaccines in 4,607 human subjects, and 324 cohort studies from the ImmPort. We hypothesized that an integrative ontological representation of the data from these studies would enhance our understanding and analysis of these ImmPort vaccine studies, and with ontological classification and tools such as VIGET, we could further study the effects of different conditions such as vaccine types and host biological sex on the vaccine response gene expression profiles. Our Vaccine Ontology (VO) analysis classified these 37 vaccines into bacterial, viral, and protozoan vaccine types with different vaccine properties. The ImmPort metadata types were modeled with the Vaccine Investigation Ontology (VIO). Our new ontology-based pipeline extracted vaccine response data from the ImmPort database, annotated them based on ontology, obtained corresponding gene expression data from the GEO, and performed consistent omics data analysis. Our use case found gene profiles shared and differed from live and killed inactivated influenza vaccines. Furthermore, our Omics data analysis using the VIGET tool found that female and male human subjects have differential host responses for influenza vaccines. For example, our study showed much stronger early female responses to influenza vaccination than males, and males was able to show active immune responses at a later stage. Interestingly, the female (but not male) human subject group also showed significantly enriched neutrophil degranulation at Day 3 after influenza vaccination; however, males (but not females) displayed significantly enriched neutrophil degranulation at Day 14 after influenza vaccination. These mechanisms have been used to find differences between the gene lists and pathways of host responses to different vaccines conditional to different factors including vaccine types and host biological sex. Moreover, this framework can be expanded to other vaccines and vaccine categories easily.