Reverse engineering and verification of gene networks: Principles, assumptions, and limitations of present methods and future perspectives

Reverse Engineering Gene Regulatory Networks by Integrating Multi-Source Biological Data

“…analytical methods in biology produces vast patterns of gene activity, highlighting the need for systematic tools to identify the architecture and dynamics of the underlying GRN (He et al 2009). Here, the system identification problem falls naturally into the category of reverse engineering; a complex genetic network underlies a massive set of expression data, and the task is to infer the connectivity of the genetic circuit (Tegner et al 2003).…”

Stages of Gene Regulatory Network Inference: the Evolutionary Algorithm Role

“…This goal has triggered significant research efforts, (e.g. He et al (2009) and references therein), which can be classified, based on the type of analysis performed, specifically: (i) expression pattern analysis, (ii) modelling from time series data and (iii) integrative modelling. Evolutionary algorithms have had an important role in the different stages of analysis, due to their flexibility and search power.…”

“…These series patterns can be modelled using mathematical tools, of which a large number have been applied to GRNs, (see e.g. He et al (2009); Lee & Tzou (2009) and references therein). Generally, the process of modelling GRNs consists of a few main steps: choosing an appropriate model, inferring parameters from data, validating the model and conducting simulations of the GRN to predict its behaviour under different conditions.…”

Fundamental limitations of network reconstruction from temporal data

“…In general, PðAÞ cannot be reconstructed from correlation or association analysis, but requires more sophisticated NR algorithms [11][12][13][14][15][16][17]25,26]; see also electronic supplementary material 1 for a summary of existing NR algorithms. However, after a decade of extensive studies, some core problems in NR remain open [27][28][29][30][31][32][33]. In particular, we still lack an identifiability analysis characterizing the conditions on the temporal data and knowledge of the coupling functions that are necessary to reconstruct a desired property PðAÞ [34,35].…”