A significant part of our biological knowledge is centered on relationships between biological entities (bio-entities) such as proteins, genes, small molecules, pathways, gene ontology (GO) terms and diseases. Accumulated at an increasing speed, the information on bio-entity relationships is archived in different forms at scattered places. Most of such information is buried in scientific literature as unstructured text. Organizing heterogeneous information in a structured form not only facilitates study of biological systems using integrative approaches, but also allows discovery of new knowledge in an automatic and systematic way. In this study, we performed a large scale integration of bio-entity relationship information from both databases containing manually annotated, structured information and automatic information extraction of unstructured text in scientific literature. The relationship information we integrated in this study includes protein–protein interactions, protein/gene regulations, protein–small molecule interactions, protein–GO relationships, protein–pathway relationships, and pathway–disease relationships. The relationship information is organized in a graph data structure, named integrated bio-entity network (IBN), where the vertices are the bio-entities and edges represent their relationships. Under this framework, graph theoretic algorithms can be designed to perform various knowledge discovery tasks. We designed breadth-first search with pruning (BFSP) and most probable path (MPP) algorithms to automatically generate hypotheses—the indirect relationships with high probabilities in the network. We show that IBN can be used to generate plausible hypotheses, which not only help to better understand the complex interactions in biological systems, but also provide guidance for experimental designs.

Automatic extraction of protein-protein interaction (PPI) information from scientific literature is important for building PPI databases, studying biological networks and discovering new biological knowledge through automatic hypothesis generation. In this paper, we present a new method for PPI extraction based on a mixture of logistic models. The method automatically clusters interaction words (words that describe the interactions of protein pairs) into groups with similar grammatical properties. Logistic models are fitted for each cluster of interaction words. Directionality of interactions is an essential piece of information for many protein interactions and important for building directed biological networks. Most of current PPI extraction methods do not extract the directional information of interactions. This is in part due to the lack of specific corpora with directionality information annotated. We introduce a new corpus, PICAD, for evaluating PPI extraction tools that includes directional annotation. The corpus is available at http://stat.fsu.edu/∼jinfeng/resources/PICAD.txt. In addition, we propose an ensemble approach using logistic regression, Bayesian Networks, and SVM for identifying PPIs. We show that using an ensemble of classifiers allows us to capture different features in the text and report an F-measure of 75.7% using our new corpus.