hino an approach for inferring hierarchical organization from regulatory networks日野推断来自监管网络的层次组织的方法.pdfVIP

HiNO: An Approach for Inferring Hierarchical Organization from Regulatory Networks ¨ Mara L. Hartsperger*, Robert Strache, Volker Stumpflen ¨ Institute of Bioinformatics and Systems Biology (MIPS), Helmholtz Zentrum Munchen – German Research Center for Environmental Health, Neuherberg, Germany Abstract Background: Gene expression as governed by the interplay of the components of regulatory networks is indeed one of the most complex fundamental processes in biological systems. Although several methods have been published to unravel the hierarchical structure of regulatory networks, weaknesses such as the incorrect or inconsistent assignment of elements to their hierarchical levels, the incapability to cope with cyclic dependencies within the networks or the need for a manual curation to retrieve non-overlapping levels remain unsolved. Methodology/Results: We developed HiNO as a significant improvement of the so-called breadth-first-search (BFS) method. While BFS is capable of determining the overall hierarchical structures from gene regulatory networks, it especially has problems solving feed-forward type of loops leading to conflicts within the level assignments. We resolved these problems by adding a recursive correction approach consisting of two steps. First each vertex is placed on the lowest level that this vertex and its regulating vertices are assigned to (downgrade procedure). Second, vertices are assigned to the next higher level (upgrade procedure) if they have successors with the same level assignment and have themselves no regulators. We evaluated HiNO by comparing it with the BFS method by applying them to the regulatory networks from Saccharomyces cerevisiae and Escherichia coli, respectively. The