Assay and Drug Development Technologies - 11

ADVANCES IN HIGH CONTENT SCREENING
information generated via HCS, has created fresh bottlenecks
for the interpretation and expert assessment of data. Without
this expert intervention, the acquisition of knowledge from
the data is problematic. Rapid methods of expert assessment
are therefore required that scale along with the increase in
data and information volume. The scientific literature is an
excellent source of expert knowledge to qualify experimental
results and search for ideas for the design of experiments, but
requires that very large numbers ofreferences be searched and
then manually read to extract the knowledge required for the
FIG. 3. Target discovery for assay design using the CellSpace Knowledge Miner component of the vHCS:Discovery Toolbox. Potential
targets of toxic compounds were mined from the scientific literature by first choosing several terms describing mechanisms of toxicity (left
column of terms describing cellular functions). Second, multiple terms associated with these modes of toxicity were generated with a
CellSpace query and then listed as potential targets for assay design in the right column. These potential HCS targets, which could be
broadly based (e.g., ''Signal Transduction'' and ''Phosphorylation'') or narrow (e.g., ''Mitosis'' and ''Cell Adhesion''), were then mapped
against the mechanisms of toxicity in the left column. Moderate (green) and high (yellow) likelihoods of co-occurrence between the two
columns of terms are shown here. For example, ''Immunologic Cytotoxicity'' often occurs with potential HCS targets such as the cell cycle,
cell adhesion, and cell movement. It should also be noted that no moderate or high likelihoods of co-occurrence were detected between
the mechanisms of toxicity listed and potential targets such as the MAP kinase signaling system or terms describing specific components of
the cell cycle. That the scientific literature has yet to focus strongly on these connections led us to choose some of these potentially new
toxicity targets as well as some of the more established physiological responses in designing the HCS assays to profile the toxic responses
of cells.
ª 2022 MARY ANN LIEBERT, INC. ASSAY and Drug Development Technologies 11

Assay and Drug Development Technologies

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