RT Journal Article
SR Electronic
T1 An extensible ontology for inference of emergent whole cell function from relationships between subcellular processes
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 112201
DO 10.1101/112201
A1 Jens Hansen
A1 David Meretzky
A1 Simeneh Woldesenbet
A1 Gustavo Stolovitzky
A1 Ravi Iyengar
YR 2017
UL http://biorxiv.org/content/early/2017/03/02/112201.abstract
AB 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.