Augmenting subnetwork inference with information extracted from the scientific literature.

Many biological studies involve either (i) manipulating some aspect of a cell or its environment and then simultaneously measuring the effect on thousands of genes, or (ii) systematically manipulating each gene and then measuring the effect on some response of interest. A common challenge that arises in these studies is to explain how genes identified as relevant in the given experiment are organized into a subnetwork that accounts for the response of interest. The task of inferring a subnetwork is typically dependent on the information available in publicly available, structured databases, which suffer from incompleteness. However, a wealth of potentially relevant information resides in the scientific literature, such as information about genes associated with certain concepts of interest, as well as interactions that occur among various biological entities. We contend that by exploiting this information, we can improve the explanatory power and accuracy of subnetwork inference in multiple applications. Here we propose and investigate several ways in which information extracted from the scientific literature can be used to augment subnetwork inference. We show that we can use literature-extracted information to (i) augment the set of entities identified as being relevant in a subnetwork inference task, (ii) augment the set of interactions used in the process, and (iii) support targeted browsing of a large inferred subnetwork by identifying entities and interactions that are closely related to concepts of interest. We use this approach to uncover the pathways involved in interactions between a virus and a host cell, and the pathways that are regulated by a transcription factor associated with breast cancer. Our experimental results demonstrate that these approaches can provide more accurate and more interpretable subnetworks. Integer program code, background network data, and pathfinding code are available at https://github.com/Craven-Biostat-Lab/subnetwork_inference Author summary There is a multitude of publicly available databases that contain information about biological entities (i.e., genes, proteins, and other small molecules) as well as information about how these entities interact together. However, these databases are often incomplete. There is a wealth of information present in the text of the scientific literature that is not yet available in these databases. Using tools that mine the scientific literature we are able to extract some of this potentially relevant information. In this work we show how we can use publicly available databases in conjunction with the information extracted from the scientific literature to infer the networks that are involved in specific biological processes, such as viral replication and cancer tumor growth.