---
_id: '15162'
abstract:
- lang: eng
  text: Cytological profiling (CP) is an unbiased image-based screening technique
    that uses automated microscopy and image analysis to profile compounds based on
    numerous quantifiable phenotypic features. We used CP to evaluate a library of
    nearly 500 compounds with documented mechanisms of action (MOAs) spanning a wide
    range of biological pathways. We developed informatics techniques for generating
    dosage-independent phenotypic “fingerprints” for each compound, and for quantifying
    the likelihood that a compound's CP fingerprint corresponds to its annotated MOA.
    We identified groups of features that distinguish classes with closely related
    phenotypes, such as microtubule poisons vs. HSP90 inhibitors, and DNA synthesis
    vs. proteasome inhibitors. We tested several cases in which cytological profiles
    indicated novel mechanisms, including a tyrphostin kinase inhibitor involved in
    mitochondrial uncoupling, novel microtubule poisons, and a nominal PPAR-gamma
    ligand that acts as a proteasome inhibitor, using independent biochemical assays
    to confirm the MOAs predicted by the CP signatures. We also applied maximal-information
    statistics to identify correlations between cytological features and kinase inhibitory
    activities by combining the CP fingerprints of 24 kinase inhibitors with published
    data on their specificities against a diverse panel of kinases. The resulting
    analysis suggests a strategy for probing the biological functions of specific
    kinases by compiling cytological data from inhibitors of varying specificities.
article_number: '2604'
article_processing_charge: No
article_type: original
author:
- first_name: Marcos H.
  full_name: Woehrmann, Marcos H.
  last_name: Woehrmann
- first_name: Walter M.
  full_name: Bray, Walter M.
  last_name: Bray
- first_name: James K.
  full_name: Durbin, James K.
  last_name: Durbin
- first_name: Sean C.
  full_name: Nisam, Sean C.
  last_name: Nisam
- first_name: Alicia Kathleen
  full_name: Michael, Alicia Kathleen
  id: 6437c950-2a03-11ee-914d-d6476dd7b75c
  last_name: Michael
- first_name: Emerson
  full_name: Glassey, Emerson
  last_name: Glassey
- first_name: Joshua M.
  full_name: Stuart, Joshua M.
  last_name: Stuart
- first_name: R. Scott
  full_name: Lokey, R. Scott
  last_name: Lokey
citation:
  ama: Woehrmann MH, Bray WM, Durbin JK, et al. Large-scale cytological profiling
    for functional analysis of bioactive compounds. <i>Molecular BioSystems</i>. 2013;9(11).
    doi:<a href="https://doi.org/10.1039/c3mb70245f">10.1039/c3mb70245f</a>
  apa: Woehrmann, M. H., Bray, W. M., Durbin, J. K., Nisam, S. C., Michael, A. K.,
    Glassey, E., … Lokey, R. S. (2013). Large-scale cytological profiling for functional
    analysis of bioactive compounds. <i>Molecular BioSystems</i>. Royal Society of
    Chemistry. <a href="https://doi.org/10.1039/c3mb70245f">https://doi.org/10.1039/c3mb70245f</a>
  chicago: Woehrmann, Marcos H., Walter M. Bray, James K. Durbin, Sean C. Nisam, Alicia
    K. Michael, Emerson Glassey, Joshua M. Stuart, and R. Scott Lokey. “Large-Scale
    Cytological Profiling for Functional Analysis of Bioactive Compounds.” <i>Molecular
    BioSystems</i>. Royal Society of Chemistry, 2013. <a href="https://doi.org/10.1039/c3mb70245f">https://doi.org/10.1039/c3mb70245f</a>.
  ieee: M. H. Woehrmann <i>et al.</i>, “Large-scale cytological profiling for functional
    analysis of bioactive compounds,” <i>Molecular BioSystems</i>, vol. 9, no. 11.
    Royal Society of Chemistry, 2013.
  ista: Woehrmann MH, Bray WM, Durbin JK, Nisam SC, Michael AK, Glassey E, Stuart
    JM, Lokey RS. 2013. Large-scale cytological profiling for functional analysis
    of bioactive compounds. Molecular BioSystems. 9(11), 2604.
  mla: Woehrmann, Marcos H., et al. “Large-Scale Cytological Profiling for Functional
    Analysis of Bioactive Compounds.” <i>Molecular BioSystems</i>, vol. 9, no. 11,
    2604, Royal Society of Chemistry, 2013, doi:<a href="https://doi.org/10.1039/c3mb70245f">10.1039/c3mb70245f</a>.
  short: M.H. Woehrmann, W.M. Bray, J.K. Durbin, S.C. Nisam, A.K. Michael, E. Glassey,
    J.M. Stuart, R.S. Lokey, Molecular BioSystems 9 (2013).
date_created: 2024-03-21T07:58:57Z
date_published: 2013-08-20T00:00:00Z
date_updated: 2024-03-25T11:45:46Z
day: '20'
doi: 10.1039/c3mb70245f
extern: '1'
intvolume: '         9'
issue: '11'
keyword:
- Molecular Biology
- Biotechnology
language:
- iso: eng
month: '08'
oa_version: None
publication: Molecular BioSystems
publication_identifier:
  eissn:
  - 1742-2051
  issn:
  - 1742-206X
publication_status: published
publisher: Royal Society of Chemistry
quality_controlled: '1'
scopus_import: '1'
status: public
title: Large-scale cytological profiling for functional analysis of bioactive compounds
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 9
year: '2013'
...