title: Decoding complex chemical mixtures with a physical model of a sensor array.
abstract: Combinatorial sensor arrays, such as the olfactory system, can detect a large number of analytes using a relatively small number of receptors. However, the complex pattern of receptor responses to even a single analyte, coupled with the non-linearity of responses to mixtures of analytes, makes quantitative prediction of compound concentrations in a mixture a challenging task. Here we develop a physical model that explicitly takes receptor-ligand interactions into account, and apply it to infer concentrations of highly related sugar nucleotides from the output of four engineered G-protein-coupled receptors. We also derive design principles that enable accurate mixture discrimination with cross-specific sensor arrays. The optimal sensor parameters exhibit relatively weak dependence on component concentrations, making a single designed array useful for analyzing a sizable range of mixtures. The maximum number of mixture components that can be successfully discriminated is twice the number of sensors in the array. Finally, antagonistic receptor responses, well-known to play an important role in natural olfactory systems, prove to be essential for the accurate prediction of component concentrations.
authors: Department of Physics & Astronomy and BioMaPS Institute for Quantitative Biology, Rutgers University, Piscataway, New Jersey, United States of America.
authors: Julia
authors: J
authors: Tsitron
authors: Addison D
authors: AD
authors: Ault
authors: James R
authors: JR
authors: Broach
authors: Alexandre V
authors: AV
authors: Morozov
mesh_terms: D000465:Algorithms; D001499:Bayes Theorem; D015374:Biosensing Techniques / Q000295:instrumentation* / Q000379:methods*; D045424:Complex Mixtures / Q000032:analysis* / Q000737:chemistry; D019295:Computational Biology; D003198:Computer Simulation; D006801:Humans; D008954:Models, Biological; D011485:Protein Binding; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D012903:Smell / Q000502:physiology; D013816:Thermodynamics; D014539:Uridine Diphosphate Sugars / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism
chemical_list: D045424:Complex Mixtures; D043562:Receptors, G-Protein-Coupled; D014539:Uridine Diphosphate Sugars