Related Experiment Video
Updated: Jun 20, 2026

High Content Screening in Neurodegenerative Diseases
Published on: January 6, 2012
Hypothesis-driven screening
Ulrich Schopfer1, Caroline Engeloch, Frank Höhn
1Novartis Institutes for BioMedical Research, Novartis Pharma AG, Basel, Switzerland.
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.
Insights
Phenotypic chemogenomics screening needs flexible strategies. A new High Throughput Cherry Picking (HTCP) system using acoustic dispensing enables hypothesis-driven experiments, improving accuracy in drug discovery.
Area of Science:
- Chemogenomics
- High-throughput screening
- Drug discovery
Background:
- Phenotypic chemogenomics studies are complex, often yielding false positives/negatives.
- Traditional High Throughput Screening (HTS) lacks flexibility for iterative, hypothesis-based experiments.
- Adapting screening for complex biological systems is crucial for effective lead identification.
Purpose of the Study:
- To introduce a novel High Throughput Cherry Picking (HTCP) system.
- To enable a new paradigm of hypothesis-driven screening in chemogenomics.
- To demonstrate the utility of HTCP in real-world chemogenomics studies.
Main Methods:
- Development of a High Throughput Cherry Picking (HTCP) system.
- Utilizing acoustic dispensing technology for precise compound handling.
- Implementing iterative, hypothesis-based experimental workflows.
Main Results:
- The HTCP system provides the necessary flexibility for hypothesis-driven experiments.
- Demonstrated successful application in three distinct chemogenomics studies.
- Improved efficiency and accuracy in identifying potential drug leads.
Conclusions:
- The HTCP system supports a more effective screening paradigm for chemogenomics.
- Hypothesis-based screening enhances the reliability of results in complex biological systems.
- This approach advances lead finding in drug discovery.
Related Concept Videos
Genetic Screens
Forward genetic screens
Forward or “classical” genetic screens involve creating random mutations in an organism’s DNA using radiation, mutagens, or insertion of additional bases, which result in visible changes...
Statistical Hypothesis Testing
Statistical significance measures the probability that an observed result occurred by chance. If this probability, known as...
Types of Hypothesis Testing
When the null and alternative hypotheses are stated, it is observed that the null hypothesis is a neutral statement against which the alternative hypothesis is tested. The alternative hypothesis is a claim that instead has a certain direction. If the null hypothesis claims that p = 0.5, the alternative hypothesis would be an opposing statement to this and can be put either p > 0.5, p < 0.5, or p ≠ 0.5.
What is a Hypothesis?
Drug Discovery: Overview
Null and Alternative Hypotheses
The null hypothesis, denoted by H0 is a statement of no difference between the variables—they are not related. This can often be considered the status quo. As a result if you cannot accept the null, it requires some action.
The alternative hypothesis, denoted by H1 or Ha, is a claim about the population that is...

