Assay and Drug Development Technologies - 13

ADVANCES IN HIGH CONTENT SCREENING
within the HCS platform, it is possible to demonstrate how high
content profiling can be used to dissect the cellular and molecular
activities of a compound library containing toxicological
agents. Furthermore, the informatics and bioinformatics
components of the platform can be leveraged to help both
design the profile by optimizing toxicity assay target selection
A
as well as building cellular knowledge through mining of the
large amounts of data contained in the results.
First, the CellSpace Knowledge Miner component of the
vHCS:Discovery Toolbox was used to extract potential targets
of the toxicity response from the scientific literature. Figure 3
shows how CellSpace was used to choose some of these
B
FIG. 5. HCS is a powerful tool for connecting the activation of molecular pathways within populations of single cells. (A) The activation of two
stress kinase pathways, p38 and extracellular signal-regulated kinase (ERK), was measured after treatment with eight toxic agents. Each row
of well-graphs defines the concentration titration of one drug and the effect it had on the activation of two kinases. Thus, each point indicates
the relative activation of p38 and ERK within a single cell. This plate-view, generated with SpotfFire data visualization software, which is
directly linked to vHCS:Discovery ToolBox, provides the user with information on the response of hundreds of thousands of cells at one time.
PMA, phorbol myristate acetate. (B) A close-up view of data from three wells is shown in A. These well-graphs demonstrate how easily drilling
down into HCS data can reveal complex cellular and molecular interrelationships, and the specific effects drugs have on them.
ª 2022 MARY ANN LIEBERT, INC. ASSAY and Drug Development Technologies 13

Assay and Drug Development Technologies

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