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WIREs Syst Biol Med
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In silico models of cancer

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Cancer is a complex disease that involves multiple types of biological interactions across diverse physical, temporal, and biological scales. This complexity presents substantial challenges for the characterization of cancer biology, and motivates the study of cancer in the context of molecular, cellular, and physiological systems. Computational models of cancer are being developed to aid both biological discovery and clinical medicine. The development of these in silico models is facilitated by rapidly advancing experimental and analytical tools that generate information‐rich, high‐throughput biological data. Statistical models of cancer at the genomic, transcriptomic, and pathway levels have proven effective in developing diagnostic and prognostic molecular signatures, as well as in identifying perturbed pathways. Statistically inferred network models can prove useful in settings where data overfitting can be avoided, and provide an important means for biological discovery. Mechanistically based signaling and metabolic models that apply a priori knowledge of biochemical processes derived from experiments can also be reconstructed where data are available, and can provide insight and predictive ability regarding the behavior of these systems. At longer length scales, continuum and agent‐based models of the tumor microenvironment and other tissue‐level interactions enable modeling of cancer cell populations and tumor progression. Even though cancer has been among the most‐studied human diseases using systems approaches, significant challenges remain before the enormous potential of in silico cancer biology can be fully realized. Copyright © 2009 John Wiley & Sons, Inc.

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Figure 1.

Molecular and physiological complexity in cancer.

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Figure 2.

Biological scales and potential modeling approaches.

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Figure 3.

Schematic overview of statistical modeling in human disease.

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Figure 4.

Comparison of biochemical reaction network and statistical network models.

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Figure 5.

Mathematical representation of reaction links in biochemical networks.

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Blanche Capel

Blanche Capel

earned her Ph.D. at the University of Pennsylvania and has been at Duke University since 1993. She earned her endowed professorship, the James B. Duke Professor of Cell Biology, for the meaningful discoveries she has made since her postdoctoral work in genetics at the National Institute for Medical Research in London. The broad goal of the research in Dr. Capel’s laboratory is to characterize the cellular and molecular basis of morphogenesis – how the body forms. She uses gonadal (gender/sex) development in the mouse as her model system and investigates a gene she helped discover, Sry, the male sex determining gene. Gonad development is unique in that a single rudimentary tissue can be induced to form one of two different organs, an ovary or testis, and she is learning all she can about this central mystery of biology.

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