assessment of network perturbation amplitudes by applying high-throughput data to causal biological networks评估网络扰动振幅通过应用高通量数据因果生物网络.pdfVIP

Martin et al. BMC Systems Biology 2012, 6:54 /1752-0509/6/54 METHODOLOGY ARTICLE Open Access Assessment of network perturbation amplitudes by applying high-throughput data to causal biological networks 1† 3† 1*† 3 1 2 3 Florian Martin , Ty M Thomson , Alain Sewer , David A Drubin , Carole Mathis , Dirk Weisensee , Dexter Pratt , Julia Hoeng 1 and Manuel C Peitsch1 Abstract Background: High-throughput measurement technologies produce data sets that have the potential to elucidate the biological impact of disease, drug treatment, and environmental agents on humans. The scientific community faces an ongoing challenge in the analysis of these rich data sources to more accurately characterize biological processes that have been perturbed at the mechanistic level. Here, a new approach is built on previous methodologies in which high-throughput data was interpreted using prior biological knowledge of cause and effect relationships. These relationships are structured into network models that describe specific biological processes, such as inflammatory signaling or cell cycle progression. This enables quantitative assessment of network perturbation in response to a given stimulus. Results: Four complementary methods were devised to quantify treatment-induced activity changes in processes described by network models. In addition, companion statistics were developed to qualify significance and specificity of the results. This approach is called Network Perturbation Amplitude (NPA) scoring because the amplitudes of treatment-induced perturbations are computed for biological network models. The NPA methods were tested on two transcriptomic data sets: normal human bronchial epithelial (NHB