Introduction: Members of the TOPMed Diabetes Working Group have computed over 200 million single-variant associations between TOPMed whole genomes and harmonized phenotypes for T2D, Fasting Glucose, Fasting Insulin and HbA1c. This massive quantity of results is typical of TOPMed research and transforming this “raw information” into “biological discovery” can be challenging. Scientist-friendly tools are needed to provide an integrated approach that includes data visualization, broad annotation, and fine-mapping techniques.

Methods: An Omics Analysis, Search and Information System (OASIS) was constructed for the TOPMed Diabetes Working Group by making major enhancements to an existing web-based application developed at the University of Maryland. The enhancements, which support the large TOPMed datasets, required redesign of the underlying database architecture and use of highly efficient data compression and data handling made available with the MMAP software (https://mmap.github.io/). The OASIS webserver is an approved “TOPMed Cloud Computing Platform” and thus allows Working Group analysts to directly upload association results for sharing and comparing alternative analyses. Multiple datasets can be created and access control features allow datasets to be selectively shared with other registered TOPMed OASIS users.

Results: OASIS datasets of up to 70 million associations from TOPMed freeze4 (219 million variants) and freeze5b (470 million) have been created for diabetes phenotypes. Boxplots split by genotype, study and ancestry are used to track populations for rare variants. Significant signals driven by a single study cohort have been identified. Variants are annotated by OASIS as they are reported during a user-initiated query and those lying in regulatory regions are easily spotted. Known-loci lists can be applied to query reports to identify variants in windows around known loci. Conditional and multi-covariate analysis is available for user-selected variants and integrated LocusZoom and Haploview plots provide linkage visualizations. Queries can be filtered by p-value, effect size, gene, variant type and/or function, rsid lists, genomic positions, and allele frequency.

Conclusion: Transforming massive volumes of TOPMed association results into “biological discovery” has been made dramatically easier. As a web-based tool, OASIS allows both analyst and non-analyst easy access to a wealth of annotation, visualization and fine-mapping techniques.