title: Hypothesis-driven screening.
abstract: Phenotypic chemogenomics studies require screening strategies that account for the complex nature of the experimental system. Unknown mechanism of action and high frequency of false positives and false negatives necessitate iterative experiments based on hypotheses formed on the basis of results from the previous step. Process-driven High Throughput Screening (HTS), aiming to "industrialize" lead finding and developed to maximize throughput, is rarely affording sufficient flexibility to design hypothesis-based experiments.In this contribution, we describe a High Throughput Cherry Picking (HTCP) system based on acoustic dispensing technology that was developed to support a new screening paradigm. We demonstrate the power of hypothesis-based screening in three chemogenomics studies that were recently conducted.
authors.affiliation: Novartis Institutes for BioMedical Research, Novartis Pharma AG, Basel, Switzerland.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Schopfer
authors.forename: Caroline
authors.initials: C
authors.lastname: Engeloch
authors.forename: Frank
authors.initials: F
authors.lastname: Höhn
authors.forename: Hervé
authors.initials: H
authors.lastname: Mees
authors.forename: Jennifer
authors.initials: J
authors.lastname: Leeds
authors.forename: Fraser
authors.initials: F
authors.lastname: Glickman
authors.forename: Günther
authors.initials: G
authors.lastname: Scheel
authors.forename: Sandrine
authors.initials: S
authors.lastname: Ferrand
authors.forename: Peter
authors.initials: P
authors.lastname: Fekkes
authors.forename: Martin
authors.initials: M
authors.lastname: Pfeifer
mesh_terms: D000162:Acoustics / Q000295:instrumentation; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology; D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology; D055808:Drug Discovery; D004353:Drug Evaluation, Preclinical / Q000295:instrumentation / Q000379:methods*; D023281:Genomics / Q000379:methods; D057166:High-Throughput Screening Assays / Q000295:instrumentation / Q000379:methods*; D008954:Models, Biological; D008967:Molecular Biology / Q000379:methods; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000254:growth & development; D013211:Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development; D014584:User-Computer Interface
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents