Title |
Protein Networks as Logic Functions in Development and Cancer
|
---|---|
Published in |
PLoS Computational Biology, September 2011
|
DOI | 10.1371/journal.pcbi.1002180 |
Pubmed ID | |
Authors |
Janusz Dutkowski, Trey Ideker |
Abstract |
Many biological and clinical outcomes are based not on single proteins, but on modules of proteins embedded in protein networks. A fundamental question is how the proteins within each module contribute to the overall module activity. Here, we study the modules underlying three representative biological programs related to tissue development, breast cancer metastasis, or progression of brain cancer, respectively. For each case we apply a new method, called Network-Guided Forests, to identify predictive modules together with logic functions which tie the activity of each module to the activity of its component genes. The resulting modules implement a diverse repertoire of decision logic which cannot be captured using the simple approximations suggested in previous work such as gene summation or subtraction. We show that in cancer, certain combinations of oncogenes and tumor suppressors exert competing forces on the system, suggesting that medical genetics should move beyond cataloguing individual cancer genes to cataloguing their combinatorial logic. |
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Geographical breakdown
Country | Count | As % |
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United States | 4 | 40% |
Switzerland | 2 | 20% |
France | 1 | 10% |
United Kingdom | 1 | 10% |
Unknown | 2 | 20% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 7 | 70% |
Scientists | 3 | 30% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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United States | 16 | 6% |
France | 4 | 1% |
Germany | 2 | <1% |
Japan | 2 | <1% |
China | 2 | <1% |
Nigeria | 2 | <1% |
India | 1 | <1% |
Canada | 1 | <1% |
Taiwan | 1 | <1% |
Other | 9 | 3% |
Unknown | 228 | 85% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 82 | 31% |
Researcher | 80 | 30% |
Student > Master | 20 | 7% |
Professor > Associate Professor | 17 | 6% |
Other | 15 | 6% |
Other | 40 | 15% |
Unknown | 14 | 5% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 146 | 54% |
Computer Science | 45 | 17% |
Biochemistry, Genetics and Molecular Biology | 27 | 10% |
Medicine and Dentistry | 7 | 3% |
Engineering | 6 | 2% |
Other | 16 | 6% |
Unknown | 21 | 8% |