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Network inference is a rapidly advancing field, with new methods being proposed on a regular basis. Understanding the advantages and limitations of different network inference methods is key to their effective application in different circumstances. The common structural properties shared by diverse networks naturally pose a challenge when it comes to devising accurate inference methods, but surprisingly, there is a paucity of comparison and evaluation methods. Historically, every new methodology has only been tested against \textit{gold standard} (true values) purpose-designed synthetic and real-world (validated) biological networks. In this paper we aim to assess the impact of taking into consideration aspects of topological and information content in the evaluation of the final accuracy of an inference procedure. Specifically, we will compare the best inference methods, in both graph-theoretic and information-theoretic terms, for preserving topological properties and the original information content of synthetic and biological networks. New methods for performance comparison are introduced by borrowing ideas from gene set enrichment analysis and by applying concepts from algorithmic complexity. Experimental results show that no individual algorithm outperforms all others in all cases, and that the challenging and non-trivial nature of network inference is evident in the struggle of some of the algorithms to turn in a performance that is superior to random guesswork. Therefore special care should be taken to suit the method to the purpose at hand. Finally, we show that evaluations from data generated using different underlying topologies have different signatures that can be used to better choose a network reconstruction method., main part: 18 pages. 21 pages with Sup Inf. Forthcoming in the journal of Seminars in Cell and Developmental Biology