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Biomedical subjects

Xiao-Jiang Feng

Publications and source records attributed to Xiao-Jiang Feng.

2 recordsLinked to original sources

Closed-loop learning control of bio-networks.

A general goal of systems biology is to acquire a detailed quantitative understanding of the life-sustaining interactions between genes and proteins. There arises an interesting question of whether these network dynamics can be controlled externally. In the open-loop approach to experimental biology, a control design would be chosen based on a desired target response and modeling with all the available knowledge about the system. If the system is not completely understood or disturbances occur, then unexpected deviations from the desired response can arise. A means to circumvent this difficulty is to optimize the controls in a closed-loop operation by modifying successive input controls based on the performance of previous controls. This paper presents a simulation of closed-loop learning control applied to biological systems in order to generate a desired response. The most powerful advantage of this technique is that the controls are deduced based on experimental results and the process can operate without a model for the underlying biochemical network. This feature eliminates the problem of faulty predictions as well as the need for a detailed understanding of the underlying molecular pathways, suggesting that biological systems can be controlled even before the post-systems biology era.

Artificial Intelligence↗

Optimizing genetic circuits by global sensitivity analysis.

Artificial genetic circuits are becoming important tools for controlling cellular behavior and studying molecular biosystems. To genetically optimize the properties of complex circuits in a practically feasible fashion, it is necessary to identify the best genes and/or their regulatory components as mutation targets to avoid the mutation experiments being wasted on ineffective regions, but this goal is generally not achievable by current methods. The Random Sampling-High Dimensional Model Representation (RS-HDMR) algorithm is employed in this work as a global sensitivity analysis technique to estimate the sensitivities of the circuit properties with respect to the circuit model parameters, such as rate constants, without knowing the precise parameter values. The sensitivity information can then guide the selection of the optimal mutation targets and thereby reduce the laboratory effort. As a proof of principle, the in vivo effects of 16 pairwise mutations on the properties of a genetic inverter were compared against the RS-HDMR predictions, and the algorithm not only showed good consistency with laboratory results but also revealed useful information, such as different optimal mutation targets for optimizing different circuit properties, not available from previous experiments and modeling.

Algorithms↗