PT - JOURNAL ARTICLE AU - Mariana Gómez-Schiavon AU - Hana El-Samad TI - Complexity-Aware Simple Modeling AID - 10.1101/248419 DP - 2018 Jan 01 TA - bioRxiv PG - 248419 4099 - http://biorxiv.org/content/early/2018/01/17/248419.short 4100 - http://biorxiv.org/content/early/2018/01/17/248419.full AB - 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‐ and large-scale approaches.HighlightsSimple or small-scale models allow deduction of fundamental principles of biological systemsDetailed or large-scale models can be quantitatively accurate but difficult to analyzeComplexity-aware simple models can extract principles that are robust to the presence of unknown complex interactionsGraphical abstract