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. 2017;22:27-38.
doi: 10.1142/9789813207813_0004.

PROSNET: INTEGRATING HOMOLOGY WITH MOLECULAR NETWORKS FOR PROTEIN FUNCTION PREDICTION

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Free PMC article

PROSNET: INTEGRATING HOMOLOGY WITH MOLECULAR NETWORKS FOR PROTEIN FUNCTION PREDICTION

Sheng Wang et al. Pac Symp Biocomput. .
Free PMC article

Abstract

Automated annotation of protein function has become a critical task in the post-genomic era. Network-based approaches and homology-based approaches have been widely used and recently tested in large-scale community-wide assessment experiments. It is natural to integrate network data with homology information to further improve the predictive performance. However, integrating these two heterogeneous, high-dimensional and noisy datasets is non-trivial. In this work, we introduce a novel protein function prediction algorithm ProSNet. An integrated heterogeneous network is first built to include molecular networks of multiple species and link together homologous proteins across multiple species. Based on this integrated network, a dimensionality reduction algorithm is introduced to obtain compact low-dimensional vectors to encode proteins in the network. Finally, we develop machine learning classification algorithms that take the vectors as input and make predictions by transferring annotations both within each species and across different species. Extensive experiments on five major species demonstrate that our integration of homology with molecular networks substantially improves the predictive performance over existing approaches.

Figures

Fig. 1
Fig. 1
An example of the heterogeneous biological network under our function prediction framework. The node set V consists of four types, {“Human protein”, “Yeast protein”, “Mouse protein”, and “Gene Ontology term”}. The edge type set R consists of five types, {“Sequence similarity”, “Protein function annotation”,“Gene Ontology relationship”,“Experimental”, and “Co-expression”}. This HBN explicitly captures interolog and transfer of annotation through heterogeneous paths across different species.
Fig. 2
Fig. 2
Comparison of using different data sources for function prediction
Fig. 3
Fig. 3
Comparison of different methods

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