2010
DOI: 10.1093/bioinformatics/btq703
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Cancer therapy design based on pathway logic

Abstract: We consider the growth factor (GF) signaling pathways, widely studied in the context of cancer. Interactions between different pathway components are modeled using Boolean logic gates. All possible single malfunctions in the resulting circuit are enumerated and responses of the different malfunctioning circuits to a 'test' input are used to group the malfunctions into classes. Effects of different drugs, targeting different parts of the Boolean circuit, are taken into account in deciding drug efficacy, thereby… Show more

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Cited by 80 publications
(79 citation statements)
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“…To obtain a comprehensive view of EGFR-mediated signaling, we collected: EGFR pathway maps from six popular databases (Croft et al, 2014;Gough, 2002;Kandasamy et al, 2010;Kanehisa et al, 2012;Nishimura, 2001;Schaefer et al, 2009); a Boolean circuit representation of growth factor signaling (Layek et al, 2011); and the related but more general mitogen-activated protein kinase (MAPK) pathway from the Kyoto Encyclopedia of Genes and Genomes (KEGG). Collectively referred to as reference pathways, these resources reflect the diverse goals and biases of different pathway curators.…”
Section: Reference Pathway Databases Fail To Explain Phosphorylation mentioning
confidence: 99%
“…To obtain a comprehensive view of EGFR-mediated signaling, we collected: EGFR pathway maps from six popular databases (Croft et al, 2014;Gough, 2002;Kandasamy et al, 2010;Kanehisa et al, 2012;Nishimura, 2001;Schaefer et al, 2009); a Boolean circuit representation of growth factor signaling (Layek et al, 2011); and the related but more general mitogen-activated protein kinase (MAPK) pathway from the Kyoto Encyclopedia of Genes and Genomes (KEGG). Collectively referred to as reference pathways, these resources reflect the diverse goals and biases of different pathway curators.…”
Section: Reference Pathway Databases Fail To Explain Phosphorylation mentioning
confidence: 99%
“…In [25] the authors apply a stuck-at fault model to simulate drug intervention in an acyclic growth factors pathway by a generateand-test method. stuck-at fault model mimics the defects on combinatorial logic circuit which were assimilated here to malignant mutations.…”
Section: Related Workmentioning
confidence: 99%
“…However, if there is a stuck-at-one fault at the output of the NAND gate with the same input vector as before, the output of the faulty circuit is one instead of zero. This notion of stuckat-faults has immediate biological relevance: on account of mutations or other structural abnormalities, a gene might become dysfunctional and hence stuck at a particular state irrespective of the signals that it is receiving from surrounding genes [27]. These biological defects can be abstracted as stuck-at faults.…”
Section: Boolean Modeling Of Prostate Cancer Signalingmentioning
confidence: 99%