We describe a new method to model gene expression from time-course gene expression data. The modelling is in terms of state-space descriptions of linear systems. A cell can be considered to be a system where the behaviours (responses) of the cell depend completely on the current internal state plus any external inputs. The gene expression levels in the cell provide information about the behaviours of the cell. In previously proposed methods, genes were viewed as internal state variables of a cellular system and their expression levels were the values of the internal state variables. This viewpoint has suffered from the underestimation of the model parameters. Instead, we view genes as the observation variables, whose expression values depend on the current internal state variables and any external input. Factor analysis is used to identify the internal state variables, and Bayesian Information Criterion (BIC) is used to determine the number of the internal state variables. By building dynamic equations of the internal state variables and the relationships between the internal state variables and the observation variables (gene expression profiles), we get state-space descriptions of gene expression model. In the present method, model parameters may be unambiguously identified from time-course gene expression data. We apply the method to two time-course gene expression datasets to illustrate it.
We have often observed unexpected state transitions of complex systems. We are thus interested in how to steer a complex system from an unexpected state to a desired state. Here we introduce the concept of transittability of complex networks, and derive a new sufficient and necessary condition for state transittability which can be efficiently verified. We define the steering kernel as a minimal set of steering nodes to which control signals must directly be applied for transition between two specific states of a network, and propose a graph-theoretic algorithm to identify the steering kernel of a network for transition between two specific states. We applied our algorithm to 27 real complex networks, finding that sizes of steering kernels required for transittability are much less than those for complete controllability. Furthermore, applications to regulatory biomolecular networks not only validated our method but also identified the steering kernel for their phenotype transitions.
BackgroundEssential proteins play an indispensable role in the cellular survival and development. There have been a series of biological experimental methods for finding essential proteins; however they are time-consuming, expensive and inefficient. In order to overcome the shortcomings of biological experimental methods, many computational methods have been proposed to predict essential proteins. The computational methods can be roughly divided into two categories, the topology-based methods and the sequence-based ones. The former use the topological features of protein-protein interaction (PPI) networks while the latter use the sequence features of proteins to predict essential proteins. Nevertheless, it is still challenging to improve the prediction accuracy of the computational methods.ResultsComparing with nonessential proteins, essential proteins appear more frequently in certain subcellular locations and their evolution more conservative. By integrating the information of subcellular localization, orthologous proteins and PPI networks, we propose a novel essential protein prediction method, named SON, in this study. The experimental results on S.cerevisiae data show that the prediction accuracy of SON clearly exceeds that of nine competing methods: DC, BC, IC, CC, SC, EC, NC, PeC and ION.ConclusionsWe demonstrate that, by integrating the information of subcellular localization, orthologous proteins with PPI networks, the accuracy of predicting essential proteins can be improved. Our proposed method SON is effective for predicting essential proteins.
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