Network reconstruction based on steady-state data. Sontag, E. Essays in Biochemistry, 45:161-176, Portland Press, 2008. abstract bibtex The ``reverse engineering problem'' in systems biology is that of unraveling of the web of interactions among the components of protein and gene regulatory networks, so as to map out the direct or local interactions among components. These direct interactions capture the topology of the functional network. An intrinsic difficulty in capturing these direct interactions, at least in intact cells, is that any perturbation to a particular gene or signaling component may rapidly propagate throughout the network, thus causing global changes which cannot be easily distinguished from direct effects. Thus, a major goal in reverse engineering is to use these observed global responses - such as steady-state changes in concentrations of active proteins, mRNA levels, or transcription rates - in order to infer the local interactions between individual nodes. One approach to solving this global-to-local problem is the ``Modular Response Analysis'' (MRA) method proposed in work of the author with Kholodenko et. al. (PNAS, 2002) and further elaborated in other papers. The basic method deals only with steady-state data. However, recently, quasi-steady state MRA has been used by Santos et. al. (Nature Cell Biology, 2007) for quantifying positive and negative feedback effects in the Raf/Mek/Erk MAPK network in rat adrenal pheochromocytoma (PC-12) cells. This paper presents an overview of the MRA technique, as well as a generalization of the algorithm to that quasi-steady state case.
@ARTICLE{essays_biochemistry,
AUTHOR = {E.D. Sontag},
JOURNAL = {Essays in Biochemistry},
TITLE = {Network reconstruction based on steady-state data},
YEAR = {2008},
OPTMONTH = {},
OPTNOTE = {},
OPTNUMBER = {},
PAGES = {161-176},
VOLUME = {45},
KEYWORDS = {systems biology, biochemical networks,
gene and protein networks, reverse engineering,
systems identification},
PUBLISHER = {Portland Press},
PDF = {../../FTPDIR/unravel_essays_biochem_reprint.pdf},
ABSTRACT = { The ``reverse engineering problem'' in systems biology
is that of unraveling of the web of interactions among the components
of protein and gene regulatory networks, so as to map out the direct
or local interactions among components. These direct interactions
capture the topology of the functional network. An intrinsic
difficulty in capturing these direct interactions, at least in intact
cells, is that any perturbation to a particular gene or signaling
component may rapidly propagate throughout the network, thus causing
global changes which cannot be easily distinguished from direct
effects. Thus, a major goal in reverse engineering is to use these
observed global responses - such as steady-state changes in
concentrations of active proteins, mRNA levels, or transcription
rates - in order to infer the local interactions between individual
nodes. One approach to solving this global-to-local problem is the
``Modular Response Analysis'' (MRA) method proposed in work of the
author with Kholodenko et. al. (PNAS, 2002) and further elaborated in
other papers. The basic method deals only with steady-state data.
However, recently, quasi-steady state MRA has been used by Santos et.
al. (Nature Cell Biology, 2007) for quantifying positive and negative
feedback effects in the Raf/Mek/Erk MAPK network in rat adrenal
pheochromocytoma (PC-12) cells. This paper presents an overview of
the MRA technique, as well as a generalization of the algorithm to
that quasi-steady state case. }
}
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(Nature Cell Biology, 2007) for quantifying positive and negative feedback effects in the Raf/Mek/Erk MAPK network in rat adrenal pheochromocytoma (PC-12) cells. This paper presents an overview of the MRA technique, as well as a generalization of the algorithm to that quasi-steady state case. ","bibtex":"@ARTICLE{essays_biochemistry,\n AUTHOR = {E.D. 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