Complexity-aware simple modeling.

Mathematical models continue to be essential for deepening our understanding of biology. On one extreme, simple or small-scale models help delineate general biological principles. However, the parsimony of detail in these models as well as their assumption of modularity and insulation make them inaccurate for describing quantitative features. On the other extreme, large-scale and detailed models can quantitatively recapitulate a phenotype of interest, but have to rely on many unknown parameters, making them often difficult to parse mechanistically and to use for extracting general principles. We discuss some examples of a new approach-complexity-aware simple modeling-that can bridge the gap between the small-scale and large-scale approaches.