Integrated Genomic and Proteomic Analyses of a Systematically Perturbed Metabolic Network

Ideker, Trey; Thórsson, Vésteinn; Ranish, Jeffrey A.; Christmas, Rowan H.; Buhler, Jeremy; Eng, Jimmy K.; Bumgarner, Roger E.; Goodlett, David R.; Aebersold, Ruedi; Hood, Leroy

doi:10.1126/science.292.5518.929

Cited by 1,807 publications

(1,281 citation statements)

References 25 publications

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“…Modeling regulatory circuits [29][30][31] and larger scale networks [32,33], reconstructing metabolic networks [34], investigating network robustness [35,36] and stochastic gene expression in biological systems [37], were among the necessary conditions for a full reemergence of systems biology.…”

Section: Twenty First Century Systems Biologymentioning

confidence: 99%

A unifying view of 21st century systems biology

Vidal

2009

FEBS Letters

119

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The idea that multi‐scale dynamic complex systems formed by interacting macromolecules and metabolites, cells, organs and organisms underlie some of the most fundamental aspects of life was proposed by a few visionaries half a century ago. We are witnessing a powerful resurgence of this idea made possible by the availability of nearly complete genome sequences, ever improving gene annotations and interactome network maps, the development of sophisticated informatic and imaging tools, and importantly, the use of engineering and physics concepts such as control and graph theory. Alongside four other fundamental “great ideas” as suggested by Sir Paul Nurse, namely, the gene, the cell, the role of chemistry in biological processes, and evolution by natural selection, systems‐level understanding of “What is Life” may materialize as one of the major ideas of biology.

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Section: Twenty First Century Systems Biologymentioning

confidence: 99%

A unifying view of 21st century systems biology

Vidal

2009

FEBS Letters

119

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“…Sophisticated electronic circuit type diagrams of a cell's molecular interactions provide limited insight (15,16). If the cell's protein interrelationships are drawn more like food webs in ecology, we are struck by their similarity (11,17). Food webs are described as "scale-free" networks (18).…”

Section: The Cell's Networkmentioning

confidence: 99%

“…Motifs may coalesce to form modules or subnetworks, which are being unraveled using genomic and proteomic data and, of course, computational methods using graph theory (11,29,(52)(53)(54) (Fig. 1).…”

Section: Modulesmentioning

confidence: 99%

Exploring the cell's network with molecular imaging

Enzmann

2006

Magnetic Resonance Imaging

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Molecular imaging is already a powerful tool for investigating molecular interactions within the cell. Interpreting molecular imaging findings will, however, take us into the more unfamiliar, nonlinear realm of networks. The network class of interest is the "scale-free" network, which characterizes not only the cell, but also surprisingly, other real work networks such as the world wide web. This network topology yields insights in how the cell is functionally organized via motifs, modules, and different types of hubs. Additional organizational information is gained from the cell's evolutionary history. Interpretation of molecular images will be deepened by a both qualitative and quantitative knowledge of the cell's network. Importantly, cell network behavior can be independent of molecular detail. For this reason, the same molecule can serve different functions in different cells or even within the same cell. Since a scalefree network's behavior is likely to be nonlinear and exhibit emergent behavior, a degree of caution is prudent in assigning cause and effect to molecular imaging findings in our effort to reengineer some of the cell's functions. Molecular imagers will need to be cognizant of the level of organization in the cell's network they are interrogating.

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“…Studies comparing mRNA and protein levels typically have shown a weak or poor correlation between them. [1][2][3][4][5] To better determine what actually is happening in a cell, one must know two things: (1) the quantities and activities of the various proteins present at a given time, and (2) the level of critical post-translational modifications that regulate these protein activities. The relative quantitation of mRNA, even on a global scale, cannot provide this information, nor can it describe the dynamics of proteinprotein interactions that may have dramatic effects on protein function.…”

Section: Introductionmentioning

confidence: 99%

Pharmacoproteomics in drug development

Witzmann

Grant

2003

Pharmacogenomics J

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The field of proteomics is taking on increased significance as the relevance of investigating and understanding protein expression in disease and drug development is appreciated. Recent advances in proteomics have been driven by the availability of numerous annotated whole-genome sequences and a broad range of technological and bioinformatic developments that underscore the complexity of the proteome. This review briefly addresses some of the various technologies that comprise Expression Proteomics and Functional Proteomics, citing examples where these emerging approaches have been applied to pharmacology, toxicology, and the development of drugs.

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Integrated Genomic and Proteomic Analyses of a Systematically Perturbed Metabolic Network

Cited by 1,807 publications

References 25 publications

A unifying view of 21st century systems biology

A unifying view of 21st century systems biology

Exploring the cell's network with molecular imaging

Pharmacoproteomics in drug development

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