Abstract
Whole cell responses arise from coordinated interactions between diverse human gene products functioning within various pathways underlying sub-cellular processes (SCP). Lower level SCPs interact to form higher level SCPs, often in a context specific manner to give rise to whole cell function. 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 and review articles. Currently, our ontology contains 5,384 genes, 753 SCPs and 19,180 expertly curated gene-SCP associations. Our algorithm to populate the SCPs with genes enables extension of the ontology on demand and the adaption of the ontology to the continuously growing cell biological knowledge. Since whole cell responses most often arise from the coordinated activity of multiple SCPs, we developed a dynamic enrichment algorithm that flexibly predicts SCP-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 SCPs together can 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 emergent whole cell functions.
Highlights
A major goal in systems biology at the cellular level is to understand how different subcellular processes (SCPs) that are organized as individual pathways or small networks[1] are integrated to give rise to whole cell functions
To allow flexible adaptation of our MBC ontology to different datasets, we developed an algorithm that allows for the identification of relationships between SCPs irrespective of whether they lie within or outside the initial taxonomy generated from the textbooks and review articles
The Molecular Biology of the Cell Ontology is designed to focus on sub-cellular activities that together give rise to whole cell function
Summary
A major goal in systems biology at the cellular level is to understand how different subcellular processes (SCPs) that are organized as individual pathways or small networks[1] are integrated to give rise to whole cell functions. Research in cell biology and biochemistry over the past fifty years has largely focused on identifying the molecular basis of cell physiology at various levels, and provides detailed descriptions of SCPs and their relationships Such SCPs are typically organized in text books as pathways or small networks. To allow flexible adaptation of our MBC ontology to different datasets, we developed an algorithm that allows for the identification of relationships between SCPs irrespective of whether they lie within or outside the initial taxonomy generated from the textbooks and review articles This algorithm allows for enrichment analyses by integrating SCPs in a context specific manner. Such integration enables the identification of those SCPs that form the basis for the whole cell function of interest
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