BackgroundThe growth in the availability of personal genomic data to nonexperts poses multiple challenges to human-computer interaction research; data are highly sensitive, complex, and have health implications for individuals and families. However, there has been little research on how nonexpert users explore their genomic data.ObjectiveWe focus on how to support nonexperts in exploring and comparing their own personal genomic report with those of other people. We designed and evaluated CrossGenomics, a novel tool for comparing personal genetic reports, which enables exploration of shared and unshared genetic variants. Focusing on communicating comparative impact, rarity, and certainty, we evaluated alternative novel interactive prototypes.MethodsWe conducted 3 user studies. The first focuses on assessing the usability and understandability of a prototype that facilitates the comparison of reports from 2 family members. Following a design iteration, we studied how various prototypes support the comparison of genetic reports of a 4-person family. Finally, we evaluated the needs of early adopters—people who share their genetic reports publicly for comparing their genetic reports with that of others.ResultsIn the first study, sunburst- and Venn-based comparisons of two genomes led to significantly higher domain comprehension, compared with the linear comparison and with the commonly used tabular format. However, results show gaps between objective and subjective comprehension, as sunburst users reported significantly lower perceived understanding and higher levels of confusion than the users of the tabular report. In the second study, users who were allowed to switch between the different comparison views presented higher comprehension levels, as well as more complex reasoning than users who were limited to a single comparison view. In the third study, 35% (17/49) reported learning something new from comparing their own data with another person’s data. Users indicated that filtering and toggling between comparison views were the most useful features.ConclusionsOur findings (1) highlight features and visualizations that show strengths in facilitating user comprehension of genomic data, (2) demonstrate the value of affording users the flexibility to examine the same report using multiple views, and (3) emphasize users’ needs in comparison of genomic data. We conclude with design implications for engaging nonexperts with complex multidimensional genomic data.