Reconstruction and validation of Saccharomyces cerevisiae iND750, a fully compartmentalized genome-scale metabolic model.
A fully compartmentalized genome-scale metabolic model of Saccharomyces cerevisiae that accounts for 750 genes and their associated transcripts, proteins, and reactions has been reconstructed and validated. All of the 1149 reactions included in this in silico model are both elementally and charge balanced and have been assigned to one of eight cellular locations (extracellular space, cytosol, mitochondrion, peroxisome, nucleus, endoplasmic reticulum, Golgi apparatus, or vacuole). When in silico predictions of 4154 growth phenotypes were compared to two published large-scale gene deletion studies, an 83% agreement was found between iND750's predictions and the experimental studies. Analysis of the failure modes showed that false predictions were primarily caused by iND750's limited inclusion of cellular processes outside of metabolism. This study systematically identified inconsistencies in our knowledge of yeast metabolism that require specific further experimental investigation.
Duarte
Natalie C
NC
Department of Bioengineering, University of California-San Diego, La Jolla, California 92093-0412, USA.
Herrgård
Markus J
MJ
Palsson
Bernhard Ø
BØ
D002451:Cell Compartmentation / Q000235:genetics*; D019295:Computational Biology; D003593:Cytoplasm / Q000235:genetics / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000235:genetics / Q000378:metabolism; D005110:Extracellular Space / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal / Q000235:genetics / Q000502:physiology; D005800:Genes, Fungal / Q000235:genetics / Q000502:physiology; D016681:Genome, Fungal; D006056:Golgi Apparatus / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D008957:Models, Genetic; D020675:Peroxisomes / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism*; D014617:Vacuoles / Q000235:genetics / Q000378:metabolism