Genomic approaches in dissecting complex biological pathways

Advances in genomic research have provided many types of large-scale data that contain rich information on various biological pathways. Intensive efforts have been made to qualitatively or quantitatively model biological pathways using these genomic data. Some general network properties, such as the scale-free property and network motifs, have been discussed and various network models have been applied to reconstruct pathways. However, there is a lack of systematic integration of prior knowledge and different genomic data in these analyses. In this review, we discuss pathway reconstruction under the consideration of the complexity embedded in the biological system, and the global and local properties of biological pathways. We review major methodologies, including clustering methods, scale-free networks models, Bayesian networks models, Boolean networks models, systems of differential equations, and data integration methods. We focus on the difficulty of each methodology in modeling biological pathways, and emphasize that different models capture different aspects of biological pathways or genomic data. The 'noisy' large-scale genomic data require the mathematical models and computational methods to be both robust and identifiable. In addition, we believe that ideal models should have the capability of incorporating various data types and these models need to be assessed through rigorous comparisons with empirical data.