Reading the palimpsest of cell interactions: What questions may we ask of the data?

Biological function depends on the composition and structure of the organism, the latter describing the organization of interactions between parts. While cells in multicellular organisms are capable of a remark- able degree of autonomy, most functions do require cell communication: the coordination of functions (growth, differentiation, and apoptosis), the compartmentalization of cellular processes, and the integra- tion of cells into higher levels of structural organization. A wealth of data on putative cell interactions has become available, yet its biological interpretation depends on our expectations about the structure of interaction networks. Here, we attempt to formulate basic questions to ask when interpreting cell inter- action data. We build on the understanding that cells fulfill two general functions: the integrity-maintain- ing and the organismal service function. We derive the expected patterns of cell interactions considering two intertwined aspects: the functional and the evolutionary. Based on these, we propose guidelines for analysis and interpretation of transcriptional cell-interactome data.