Characterization and prediction of haploinsufficiency using systems-level gene properties in yeast.
Variation in gene copy number can significantly affect organism fitness. When one allele is missing in a diploid, the phenotype can be compromised because of haploinsufficiency. In this work, we identified associations between Saccharomyces cerevisiae gene properties and genome-scale haploinsufficiency phenotypes from previous work. We compared the haploinsufficiency profiles against 23 gene properties and found that genes with higher level of connectivity (degree) in a protein-protein interaction network, higher genetic interaction degree, greater gene sequence conservation, and higher protein expression were significantly more likely to be haploinsufficient. Additionally, haploinsufficiency showed negative relationships with cell cycle regulation and promoter sequence conservation.
Faculty of Life Sciences, University of Manchester, Manchester, Lancashire, M13 9PT, United Kingdom.
Matthew
M
Norris
Simon
S
Lovell
Daniela
D
Delneri
D019540:Area Under Curve; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D053263:Gene Regulatory Networks; D016681:Genome, Fungal; D057895:Haploinsufficiency / Q000235:genetics*; D016366:Open Reading Frames / Q000235:genetics; D010641:Phenotype; D011401:Promoter Regions, Genetic; D060066:Protein Interaction Maps / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D012372:ROC Curve; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D012568:Schizosaccharomyces / Q000235:genetics
D018797:Cell Cycle Proteins; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins
correlation; genome; haploinsufficiency; machine-learning; prediction