The molecular circuits of tissues and cell types in the human body

”Right now, you are breathing air, digesting food, detoxifying chemicals, growing hair, making new skin cells, filtering blood, fighting would-be invaders, regulating temperature, hearing, reading, thinking and, by this stage of the sentence, probably indulging in some introspection.” – Jamie Davis, Life Unfolding.
Our body has 200-300 different types of cells, each performing a radically different function. But underneath it all, each cell carries the same set of ~25,000 core genetic components (genes). Like most complex systems, then, the diversity emerges from how these components are wired together differently in different types of cells and tissues. Charting out the large molecular circuit in each cell type is fundamental to our understanding of how genes function, what specific mutations cause disease, and how drugs might cause therapeutic and adverse effects. Towards this goal, we developed a Bayesian framework that integrates thousands of publicly available genomic datasets to computationally predict tissue-specific relationships between genes in each of 144 specific human cell-types and tissues. We demonstrate that these gene networks effectively predict tissue-specific response to perturbation of genes, and connect the roles of genes in specific tissues/cell-types to common diseases. Our work helps define the plasticity of the genome in complex organisms in health and disease.