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The Human Functional Genomics Project, a collaboration between teams in Boston and the Netherlands, aims to combine omics technology with functional tests to characterize how genetic makeup, environment and the microbiome impact immunity and health. In a series of studies, over 500 healthy volunteers were assessed for the effect of intrinsic and environmental factors (ter Horst et al.), host genomic variants (Li et al.) and intestinal flora (Schirmer et al.) on cytokine production and baseline immune parameters. The studies profiled peripheral blood in response to natural conditions or in vitro pathological or physiological stimulation; they revealed factors, including novel candidate genetic loci and microbial mediators, that affect individual human immune responses.