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Theoretical methods for predicting gene function III. Predicting protein function by genomic context Inspired by: Huynen et al. (2000), Genome research 10,1204-1210 Predicting Protein Function by Genomic Context: Qualitative Evaluation and Quantitative Inferences. S. Wodak, ULB
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Theoretical methods for predicting gene function III. Predicting protein function by genomic context Inspired by: Huynen et al. (2000), Genome research 10,1204-1210 Predicting Protein Function by Genomic Context: Qualitative Evaluation and Quantitative Inferences S. Wodak, ULB Inter-university DEA/DES in Bioinformatics
[4] Use information on genome context Gene order; co-regulation Pathway/process reconstruction 1-Gene fusion/fission analysis 2-Conservation of the local genomic context (in different genomes) -as neighbours -in runs (genes with the same direction of translation, separated by fewer than 300 bases) 3-Similar patterns of gene co-occurence in different genomes phylogenic profiles 4-Metabolic reconstruction
Domain swapping 1-Gene fusion/fission analysis Marcotte et al., (1999) Scence, 285, 751-753 Enright et al. (1999) Nature, 402, 86-90 Proteins from genes whose homologs are fused (especially if they are orthologs of the fused genes) tend to have a related function... Protein Interactions ?? Human Succinyl Co-A-transferase E. coli acetate Co-A-transferase a E. coli acetate Co-A-transferase b
2-Conservation of the local genomic context (in different genomes) deoB : Phosphoribomutase Pmm : phosphomannomutases, phosphoglucomutases Generally genomic context provides information on the process in which a gene is involved
3- Phylogenic profiles Similar patterns of gene co-occurrence in different genomes Pellegrini et al. (1999) SC p2 p1 p2 p7 p3 p4 p5 p5 Phylogenic profile p6 EC SC BS HI p1 1 0 1 p2 1 1 0 p3 0 1 1 p4 1 0 0 p5 1 1 1 p6 0 1 1 p7 1 1 0 p3 p1 p7 p1 p2 p3 p4 p6 p5 p6 p7 p5 BS EC HI p2 & p7 are functionally linked p3 & p6 are functionally linked
2-Conservation of the local genomic context (in different genomes) 5th gene is missing Nucleoside salvage pathway deoB ? deoD deoC deoA cdd pmm M. genitalium deoD pmm M. tuberculosis deoB : Phosphoribomutase Pmm : phosphomannomutases, phosphoglucomutases Generally genomic context provides information on the process in which a gene is involved