TY - JOUR T1 - An extensible ontology for inference of emergent whole cell function from relationships between subcellular processes JF - bioRxiv DO - 10.1101/112201 SP - 112201 AU - Jens Hansen AU - David Meretzky AU - Simeneh Woldesenbet AU - Gustavo Stolovitzky AU - Ravi Iyengar Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/03/02/112201.abstract N2 - Whole cell responses arise from coordinated interactions between diverse human gene products that make up various pathways for sub-cellular processes (SCP). Lower level SCPs interact to form higher level SCPs, often in a context specific manner. We sought to determine if capturing such relationships enables us to describe the emergence of whole cell functions from interacting SCPs. We developed the “Molecular Biology of the Cell” ontology based on standard cell biology and biochemistry textbooks. Currently, our ontology contains 754 SCPs and 18,989 expertly curated gene-SCP associations. In contrast with other ontologies, our algorithm to populate the SCPs with genes is flexible and enables extension of the ontology on demand. Since cell biological knowledge is constantly growing we developed a dynamic enrichment algorithm for the prediction of SCP relationships beyond the current taxonomy. This algorithm enables us to identify interactions between SCPs as a basis for higher order function in a context dependent manner, allowing us to provide a detailed description of how these SCPs together give rise to whole cell functions. We conclude that this ontology can, from omics data sets, enable the development of detailed SCP networks for predictive modeling of human cell biological functions. ER -