Methods for identifying drug targets based on genomic sequence data

Abstract

This invention provides a computational approach to identifying potential antibacterial drug targets based on a genome sequence and its annotation. Starting from a fully sequenced genome, open reading frame assignments are made which determine the metabolic genotype for the organism. The metabolic genotype, and more specifically its stoichiometric matrix, are analyzed using flux balance analysis to assess the effects of genetic deletions on the fitness of the organism and its ability to produce essential biomolecules required for growth.

1 - 23 . (canceled) 
     
     
         24 . A memory storing data for access by a software program being executed by at least one processor, comprising:
 a genome specific stoichiometric matrix stored in said memory, said genome specific stoichiometric matrix storing substrates, products, and stoichiometry for a plurality of metabolic reactions specific to an organism,   wherein at least one of said metabolic reactions corresponds to a potential function of a candidate protein that is encoded by an open reading frame of the organism's genome and for which a function is not known; and   instructions for causing the at least one processor to add or remove constraints on fluxes through the plurality of metabolic reactions so as to identify a gene coding for the candidate protein.   
     
     
         25 . The memory of  claim 24 , wherein the potential function is based on homology of the open reading frame to a nucleotide encoding a protein of known function in another organism. 
     
     
         26 . The memory of  claim 24 , wherein the potential function is based on homology of an amino acid sequence of the candidate protein to an amino acid sequence of a protein of known function in another organism. 
     
     
         27 . The memory of  claim 24 , wherein said memory is selected from the group consisting of: a hard disk, optical memory, Random Access Memory, Read Only Memory and Flash Memory. 
     
     
         28 . The memory of  claim 24 , wherein said organism is  Escherichia coli.