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=== Chemical combination effects predict connectivity in biological systems ===

==== general idea ====
 * study the effect of pathway connectivity on drug interactions (quantitatively measured as combined effect curve)
   * ~-''connectivity'' is a more general concept than ''interaction'', as it includes the topology of the pathway in which the protein takes part-~
 * a typical synergic effect in the combined drug response curve: (missing picture)
 * the model of metabolic pathway probed: (missing picture)

==== main findings (understood) ====
 * pathway topology is the outstanding factor determining the shape of the combined effect curve<<BR>>
 (assessed by systematic random perturbation of the kinetic parameters)
 * linear additive effect arise when two drugs target the same reaction
 * epistatic effect arise when 
   * two drug targets are serially connected in a linear pathway<<BR>>
   the combined effect is even less effective if the serial pathway has a significant bypass<<BR>>
   * or when two drugs act on different branches converging onto an AND gate
 * synergic effects typically arise when drug targets act on different branches converging onto an OR gate

==== main findings (not understood) ====
 * the meaning of the response curve tagged ''Potentiation''
 * the effect of negative feedback in determining the curve shape
 * why they chose as biochemical system the S. cer. sterol pathway, which has negative feedbacks, but not OR/AND branches
 * the conclusion from studies on human cancer cells, and signaling pathways