Systems medicine aims to understand the basis of wellness and disease. Here, Price et al. report findings from the Pioneer 100 Wellness Project, a collection of data from 108 individuals over 9 months - including whole genome sequences, clinical tests, metabolomes, proteomes, microbiomes and frequent activity measurements. Generation of a correlation network revealed communities of related analytes associated with physiology and disease and enabled the identification of known and candidate biomarkers. Personal data enabled recommendation of individual lifestyle changes, which improved clinical biomarkers.