Method for analyzing signaling networks in complex cellular systems
| Autor: | Brian Nakao, Eugene C. Butcher, Oksana Sirenko, Jennifer Melrose, Ellen L. Berg, Yuker Wang, Ivan Plavec, Sylvie Privat, Maya Dajee, Evangelos Hytopoulos |
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| Jazyk: | angličtina |
| Rok vydání: | 2004 |
| Předmět: |
Cell signaling
Multidisciplinary MAP Kinase Signaling System Tumor Necrosis Factor-alpha Systems biology Endothelial Cells Computational biology Biology Biological Sciences Proteomics Cell biology Interferon-gamma Humans Human genome DNA microarray Signal transduction Protein kinase A Function (biology) Cells Cultured Interleukin-1 Signal Transduction |
| Popis: | Now that the human genome has been sequenced, the challenge of assigning function to human genes has become acute. Existing approaches using microarrays or proteomics frequently generate very large volumes of data not directly related to biological function, making interpretation difficult. Here, we describe a technique for integrative systems biology in which: ( i ) primary cells are cultured under biologically meaningful conditions; ( ii ) a limited number of biologically meaningful readouts are measured; and ( iii ) the results obtained under several different conditions are combined for analysis. Studies of human endothelial cells overexpressing different signaling molecules under multiple inflammatory conditions show that this system can capture a remarkable range of functions by a relatively small number of simple measurements. In particular, measurement of seven different protein levels by ELISA under four different conditions is capable of reconstructing pathway associations of 25 different proteins representing four known signaling pathways, implicating additional participants in the NF-κBorRAS/mitogen-activated protein kinase pathways and defining additional interactions between these pathways. |
| Databáze: | OpenAIRE |
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