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  • American Association for the Advancement of Science (AAAS)  (3)
  • 1
    Online Resource
    Online Resource
    American Association for the Advancement of Science (AAAS) ; 2005
    In:  Science Vol. 308, No. 5721 ( 2005-04-22), p. 523-529
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 308, No. 5721 ( 2005-04-22), p. 523-529
    Abstract: Machine learning was applied for the automated derivation of causal influences in cellular signaling networks. This derivation relied on the simultaneous measurement of multiple phosphorylated protein and phospholipid components in thousands of individual primary human immune system cells. Perturbing these cells with molecular interventions drove the ordering of connections between pathway components, wherein Bayesian network computational methods automatically elucidated most of the traditionally reported signaling relationships and predicted novel interpathway network causalities, which we verified experimentally. Reconstruction of network models from physiologically relevant primary single cells might be applied to understanding native-state tissue signaling biology, complex drug actions, and dysfunctional signaling in diseased cells.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    RVK:
    RVK:
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2005
    detail.hit.zdb_id: 128410-1
    detail.hit.zdb_id: 2066996-3
    detail.hit.zdb_id: 2060783-0
    SSG: 11
    Location Call Number Limitation Availability
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  • 2
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 332, No. 6030 ( 2011-05-06), p. 687-696
    Abstract: Flow cytometry is an essential tool for dissecting the functional complexity of hematopoiesis. We used single-cell “mass cytometry” to examine healthy human bone marrow, measuring 34 parameters simultaneously in single cells (binding of 31 antibodies, viability, DNA content, and relative cell size). The signaling behavior of cell subsets spanning a defined hematopoietic hierarchy was monitored with 18 simultaneous markers of functional signaling states perturbed by a set of ex vivo stimuli and inhibitors. The data set allowed for an algorithmically driven assembly of related cell types defined by surface antigen expression, providing a superimposable map of cell signaling responses in combination with drug inhibition. Visualized in this manner, the analysis revealed previously unappreciated instances of both precise signaling responses that were bounded within conventionally defined cell subsets and more continuous phosphorylation responses that crossed cell population boundaries in unexpected manners yet tracked closely with cellular phenotype. Collectively, such single-cell analyses provide system-wide views of immune signaling in healthy human hematopoiesis, against which drug action and disease can be compared for mechanistic studies and pharmacologic intervention.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    RVK:
    RVK:
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2011
    detail.hit.zdb_id: 128410-1
    detail.hit.zdb_id: 2066996-3
    detail.hit.zdb_id: 2060783-0
    SSG: 11
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 3
    Online Resource
    Online Resource
    American Association for the Advancement of Science (AAAS) ; 2002
    In:  Science's STKE Vol. 2002, No. 148 ( 2002-09-03)
    In: Science's STKE, American Association for the Advancement of Science (AAAS), Vol. 2002, No. 148 ( 2002-09-03)
    Abstract: The modeling of cellular signaling pathways is an emerging field. Sachs et al. illustrate the application of Bayesian networks to an example cellular pathway involving the activation of focal adhesion kinase (FAK) and extracellular signal-regulated kinase (ERK) in response to fibronectin binding to an integrin. They describe how to use the analysis to select from among proposed models, formulate hypotheses regarding component interactions, and uncover potential dynamic changes in the interactions between these components. Although the data sets currently available for this example problem are too small to definitively point to a particular model, the approach and results provide a glimpse into the power that these methods will achieve once the technology for obtaining the necessary data becomes readily available.
    Type of Medium: Online Resource
    ISSN: 1525-8882
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2002
    Location Call Number Limitation Availability
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