Hypothesis-driven screening.
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.
Schopfer
Ulrich
U
Novartis Institutes for BioMedical Research, Novartis Pharma AG, Basel, Switzerland.
Engeloch
Caroline
C
Höhn
Frank
F
Mees
Hervé
H
Leeds
Jennifer
J
Glickman
Fraser
F
Scheel
Günther
G
Ferrand
Sandrine
S
Fekkes
Peter
P
Pfeifer
Martin
M
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
D000900:Anti-Bacterial Agents; D000935:Antifungal Agents