Suggested Changes to Model Structure Based on the Gene Deletion Study
ORF | Gene | Reason for false predictiona | Suggested change and comments |
|---|---|---|---|
| YPL188W | POSS | Mod | Change the model so that only Pos5p can provide NADPH in mitochondria |
| YMR267W | PPA2 | Mod | Force the model to use Ppa2p instead of the cytoplasmic isoforms by restricting phosphate transport out of the mitochondria. |
| YMR202W | ERG2 | Mod | Modify the interconversion between zymosterol and ergosterol biosynthesis to require ERG2. |
| YLR056W | ERG3 | Mod | See ERG2. |
| YML008C | ERG6 | Mod | See ERG2. |
| YDR178W | SDH4 | Iso | Make Sdh4p a nonessential part of the succinate dehydrogenase complex. |
| YML123C | PHO84 | Iso | There are multiple alternative isozymes for the phosphate transporters, but Pho84p should be the dominant one. |
| YBR069C | TAT1 | Iso | There are multiple alternative isozymes for amino acid transporters in the model, but they need to be made less efficient than Tat1p. |
| YLR081W | GAL2 | Iso | Model includes other isozymes (HXT genes) that are not nearly as efficient for gal transport, so disabling their gal transport ability should result in a correct prediction. |
| YMR105C | PGM2 | Iso | Pgm2p is major isoform of phosphoglucomutase; do not allow the minor isoform (Pgm1p) to fully compensate for loss of Pgm2p. |
| YHR137W | ARO9 | Iso | Aro8p should be able to compensate for ARO9 deletion on minimal media; modify the gene-protein-reaction association to reflect this. |
| YGL125W | MET13 | Iso | Met13p is the dominant isozyme; do not allow isozyme (Met12p) to compensate fully for the loss of Met13p. |
| YHR046C | INM1 | Iso | Add the gene product of YDR287W as an isozyme for Inm1p. |
| YHR001WA | QCR10 | Iso | This subunit should be made a nonessential part of the cytochrome bc1 complex since it only plays a structural role. |
| YFR033C | QCR6 | Iso | Deletion of QCR6 does not have significant effect on the formation or stability of cytochrome bc complex so that it should not play an essential role in complex formation. |
| YKL067W | YNK1 | Iso | Null mutant retains 10% of nucleoside diphosphate kinase activity. Sources of remaining enzyme activity are unknown. Reaction without gene associations should be added to the model to represent these unidentified enzymes. |
| YLR304C | ACO1 | Iso | The isozyme coded by YJL200C should not be able to fully compensate for ACO1 deletion. |
| YNL052W | COX5A | Iso | Cox5Ap is the dominant isoform; Cox5Bp should not be able to fully compensate. |
| YKL148C | SDH1 | Iso | Sdh1p should not be considered to be an essential part of the succinate dehydrogenase complex. |
| YGL008C | PMA1 | Iso | This is the major isoform of the cytosolic ATPase, but in the model a minor isoform (which contains Pma2p instead of Pma1p) can compensate for the function. Do not allow the minor isoform to fully compensate for the loss of the major isoform. |
| YLR342W | FKS1 | Iso | There are three alternate isozymes in the model, but Fks1p should be made the dominant isozyme. |
| YHR183W | GND1 | Iso | This is the major isozyme (80% of activity); other isozymes should be made less efficient. |
| YLR044C | PDC1 | Iso | There are three alternate isozymes in the model, but PDC1 deletion alone is sufficient to reduce pyruvate decarboxylase activity significantly enough to result in a slow growth phenotype. Should have Pdc1p as the major isozyme. |
| YJR148W | BAT2 | Iso | BAT2 single deletion should not be lethal as there is a mitochondrial isozyme (Bat1p); double deletion should be lethal. Bat1p currently does not catalyze valine transamination so this functionality should be added. |
| YCL009C | ILV6 | Iso | Ilv6p is the regulatory subunit of phenylalanine transaminase. This subunit should be made nonessential for the enzymatic function. |
| YAL038W | CDC19 | Reg | Pyk2p isozyme should only be expressed under conditions of very low glycolytic flux. |
| YOL086C | ADH1 | Reg | This isozyme (out of five) should be the only one active under severely glucose repressed conditions. |
a The reasons for false predictions have been classified as model structure-related (Mod), gene-protein-reaction association-related (Iso), or transcriptional regulation related (Reg). See Supplemental materials as well as http://systemsbiology.ucsd.edu for more details.