Model-based assessment of mammalian cell metabolic functionalities using omics data
Anne Richelle, Benjamin P. Kellman, Alexander T. Wenzel, Austin W.T. Chiang, Tyler Reagan, Jahir M. Gutierrez, Chintan Joshi, Shangzhong Li, Joanne K. Liu, Helen O. Masson, Jooyong Lee, Zerong Li, Laurent Heirendt, Christophe Trefois, Edwin F. Juarez, Tyler Bath, David Borland, Jill P. Mesirov, Kimberly Robasky, Nathan E. Lewis
Abstract
Omics experiments are ubiquitous in biological studies, leading to a deluge of data. However, it is still challenging to connect changes in these data to changes in cell functions because of complex interdependencies between genes, proteins, and metabolites. Here, we present a framework allowing researchers to infer how metabolic functions change on the basis of omics data. To enable this, we curated and standardized lists of metabolic tasks that mammalian cells can accomplish. Genome-scale metabolic networks were used to define gene sets associated with each metabolic task. We further developed a framework to overlay omics data on these sets and predict pathway usage for each metabolic task. We demonstrated how this approach can be used to quantify metabolic functions of diverse biological samples from the single cell to whole tissues and organs by using multiple transcriptomic datasets. To facilitate its adoption, we integrated the approach into GenePattern (www.genepattern.org-CellFie).