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Full-genomic Network Inference for Non-model organisms: A Case Study for the Fungal Pathogen Candida albicans

Authors: Jörg Linde, Ekaterina Buyko, Robert Altwasser, Udo Hahn, Reinhard Guthke


Reverse engineering of full-genomic interaction networks based on compendia of expression data has been successfully applied for a number of model organisms. This study adapts these approaches for an important non-model organism: The major human fungal pathogen Candida albicans. During the infection process, the pathogen can adapt to a wide range of environmental niches and reversibly changes its growth form. Given the importance of these processes, it is important to know how they are regulated. This study presents a reverse engineering strategy able to infer fullgenomic interaction networks for C. albicans based on a linear regression, utilizing the sparseness criterion (LASSO). To overcome the limited amount of expression data and small number of known interactions, we utilize different prior-knowledge sources guiding the network inference to a knowledge driven solution. Since, no database of known interactions for C. albicans exists, we use a textmining system which utilizes full-text research papers to identify known regulatory interactions. By comparing with these known regulatory interactions, we find an optimal value for global modelling parameters weighting the influence of the sparseness criterion and the prior-knowledge. Furthermore, we show that soft integration of prior-knowledge additionally improves the performance. Finally, we compare the performance of our approach to state of the art network inference approaches.

Keywords: Modelling, Reverse Engineering, pathogen, network inference, Linear Regression, Candida albicans, LASSO, mutual information, text-mining

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