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Systems cell biology knowledge created from high content screening

Giuliano, KA and Cheung, WS and Curran, DP and Day, BW and Kassick, AJ and Lazo, JS and Nelson, SG and Shin, Y and Taylor, DL (2005) Systems cell biology knowledge created from high content screening. Assay and Drug Development Technologies, 3 (5). 501 - 514. ISSN 1540-658X

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High content screening (HCS), the large-scale automated analysis of the temporal and spatial changes in cells and cell constituents in arrays of cells, has the potential to create enormous systems cell biology knowledge bases. HCS is being employed along with the continuum of the early drug discovery process, including lead optimization where new knowledge is being used to facilitate the decision-making process. We demonstrate methodology to build new systems cell biology knowledge using a multiplexed HCS assay, designed with the aid of knowledge-mining tools, to measure the phenotypic response of a panel of human tumor cell types to a panel of natural product-derived microtubule-targeted anticancer agents and their synthetic analogs. We show how this new systems cell biology knowledge can be used to design a lead compound optimization strategy for at least two members of the panel, (-)-laulimalide and (+)-discodermolide, that exploits cell killing activity while minimally perturbing the regulation of the cell cycle and the stability of microtubules. Furthermore, this methodology can also be applied to basic biomedical research on cells. © Mary Ann Liebert, Inc.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Giuliano, KA
Cheung, WS
Curran, DPcurran@pitt.eduCURRAN
Day, BW
Kassick, AJ
Lazo, JS
Nelson, SG
Shin, Y
Taylor, DL
Date: 1 October 2005
Date Type: Publication
Journal or Publication Title: Assay and Drug Development Technologies
Volume: 3
Number: 5
Page Range: 501 - 514
DOI or Unique Handle: 10.1089/adt.2005.3.501
Schools and Programs: Dietrich School of Arts and Sciences > Chemistry
Refereed: Yes
ISSN: 1540-658X
MeSH Headings: Antineoplastic Agents--administration & dosage; Artificial Intelligence; Biological Assay--instrumentation; Biological Assay--methods; Cell Culture Techniques--instrumentation; Cell Culture Techniques--methods; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical--instrumentation; Drug Evaluation, Preclinical--methods; Humans; Robotics--methods; Systems Biology--instrumentation; Systems Biology--methods; Tumor Cells, Cultured--cytology; Tumor Cells, Cultured--drug effects; Tumor Cells, Cultured--physiology
PubMed ID: 16305307
Date Deposited: 22 Jul 2013 17:34
Last Modified: 02 Feb 2019 15:55


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