title: Modeling error in experimental assays using the bootstrap principle: understanding discrepancies between assays using different dispensing technologies.
abstract: All experimental assay data contains error, but the magnitude, type, and primary origin of this error is often not obvious. Here, we describe a simple set of assay modeling techniques based on the bootstrap principle that allow sources of error and bias to be simulated and propagated into assay results. We demonstrate how deceptively simple operations--such as the creation of a dilution series with a robotic liquid handler--can significantly amplify imprecision and even contribute substantially to bias. To illustrate these techniques, we review an example of how the choice of dispensing technology can impact assay measurements, and show how large contributions to discrepancies between assays can be easily understood and potentially corrected for. These simple modeling techniques--illustrated with an accompanying IPython notebook--can allow modelers to understand the expected error and bias in experimental datasets, and even help experimentalists design assays to more effectively reach accuracy and imprecision goals.
authors.affiliation: Computational Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA. sonya.hanson@choderalab.org.
authors.forename: Sonya M
authors.initials: SM
authors.lastname: Hanson
authors.affiliation: Collaborations in Chemistry, Fuquay-Varina, NC, 27526, USA.
authors.forename: Sean
authors.initials: S
authors.lastname: Ekins
authors.affiliation: Computational Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA. john.chodera@choderalab.org.
authors.forename: John D
authors.identifier: http://orcid.org/0000-0003-0542-119X
authors.initials: JD
authors.lastname: Chodera
mesh_terms: D000162:Acoustics / Q000295:instrumentation*; D000465:Algorithms; D000818:Animals; D003198:Computer Simulation; D004353:Drug Evaluation, Preclinical / Q000295:instrumentation; D057075:Enzyme Assays / Q000295:instrumentation*; D004867:Equipment Design; D006801:Humans; D020128:Inhibitory Concentration 50; D008954:Models, Biological; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D036224:Receptor, EphB4 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D035501:Uncertainty
chemical_list: D047428:Protein Kinase Inhibitors; D036224:Receptor, EphB4
keywords: Acoustic droplet ejection; Assay modeling; Bootstrap principle; Direct dispensing; Dispensing technologies; Error modeling; Liquid handling