Presently disclosed are methods for inferring a network model of the interactions of biological molecules and systems for practicing such methods. The systems and methods described herein provide a systematic and computationally feasible solution to the problem of rational inference of the architecture of biological networks, based on a combination of rational and statistical evaluations of quantitative and qualitative data. These methods constrain the search space of possible networks and, in some embodiments, allow the online addition of new data into an existing model without any interruption in analysis. Additionally, these methods can provide a quantitative evaluation of the confidence levels associated with the putative network architectures discovered thereby. The methods naturally incorporate latent nodes in the search space of possible architectures; hence, the system is also capable of predicting new interactions and/or substrates for the biological systems being studied.
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