Given the many cell types and molecular components of the human immune system, along
with vast variations across individuals, how should we go about developing causal and
predictive explanations of immunity? A central strategy in human studies is to leverage
natural variation to find relationships among variables, including DNA variants, epigenetic
states, immune phenotypes, clinical descriptors, and others. Here, we focus on how natural
variation is used to find patterns, infer principles, and develop predictive models for two …