Antibiotic resistance causation identification

Abstract

A system to identify genes that confer antibiotic resistance, comprising: a processor configured to: (i) identify a set of genes present in a sample of genome sequences sequenced from potentially pathogenic isolates; (ii) generate a genome sequence without the identified set of genes; (iii) generate a gene presence-absence matrix listing the genes present in each of the genome sequences, comprising an identification of each of the plurality of genes and an identification of each of the plurality of genome sequences, and comprising an identification of whether each of the genome sequences is obtained from an organism resistant to at least one antibiotic, and further comprising an identification of either presence or absence of the respective gene within the respective genome sequence; and (iv) identify at least one gene or mutation in the plurality of genome sequences associated with antibiotic resistance; and a user interface configured to provide a report.

What is claimed is: 
     
         1 . A system configured to identify one or more genes that confer antibiotic resistance, the system comprising:
 a reference genome sequence;   a plurality of genome sequences, each of the plurality of genome sequences comprising a plurality of genes and sequenced from a potentially pathogenic isolate;   a memory;   a processor configured to: (i) identify, using the reference genome sequence, a set of genes present in a sample of the plurality of genome sequences; (ii) generate in the memory, by removing the identified set of genes from each of the plurality of genome sequences containing the identified set of genes, a genome sequence without the identified set of genes, wherein the steps of identifying a set of genes and generating a genome sequence without the identified set of genes are iterated at least once to generate data regarding which genes are present in each of the plurality of genome sequences; (iii) generate, in the memory, a gene presence-absence matrix that lists the genes present in each of the plurality of genome sequences, the presence-absence matrix comprising an identification of each of the plurality of genes within either a first column or a first row of the matrix and an identification of each of the plurality of genome sequences within the other of the either the first column or the first row, and comprising an identification, in either a row or column, of whether each of the genome sequences is obtained from an organism resistant to at least one antibiotic, and further comprising, in each intersecting cell of the presence-absence matrix, an identification of either presence of the respective gene or absence of the gene within the respective genome sequence; and (iv) identify at least one gene or mutation in the plurality of genome sequences that is associated with antibiotic resistance based at least in part on which samples and mutations confer antibiotic resistance; and   a user interface configured to output a report to a user identifying the at least one gene or mutation that is associated with antibiotic resistance for one or more of the plurality of genome sequences.   
     
     
         2 . The system of  claim 1 , wherein the processor is further configured to assign a value representing the identified at least one gene's contribution to antibiotic resistance or antibiotic sensitivity. 
     
     
         3 . The system of  claim 1 , wherein the processor is further configured to determine whether at least two of the identified genes or mutations operate as a network. 
     
     
         4 . The system of  claim 1 , wherein presence of a gene present within the respective genome sequence is defined by a binary value or a percentage in the gene presence-absence matrix. 
     
     
         5 . The system of  claim 1 , wherein the processor is further configured to determine whether at least two genes that operate as an operon network comprise a mutation. 
     
     
         6 . The system of  claim 1 , wherein the processor is further configured to classify the at least one gene identified as conferring antibiotic resistance as host or foreign using at least one of sequence composition and phylogeny. 
     
     
         7 . The system of  claim 1 , wherein the report comprises an identification of the at least one gene or mutation associated with antibiotic resistance for each of the plurality of genome sequences. 
     
     
         8 . The system of  claim 1 , wherein the processor is further configured to assign a label of resistant or sensitive to each identified mutation. 
     
     
         9 . The system of  claim 1 , wherein the processor is further configured to assign a label of resistant or sensitive for each of the plurality of genome samples. 
     
     
         10 . The system of  claim 1 , wherein the report comprises an identification of one or more SNPs associated with antibiotic resistance. 
     
     
         11 . The system of  claim 1 , wherein the potentially pathogenic isolate is obtained from a person. 
     
     
         12 . The system of  claim 11 , wherein the person is a patient. 
     
     
         13 . The system of  claim 1 , further comprising an identification of whether each potentially pathogenic isolate is resistant or sensitive to one or more antibiotics. 
     
     
         14 . The system of  claim 13 , wherein the identification of resistant or sensitive is based on a threshold. 
     
     
         15 . The system of  claim 1 , wherein the gene presence-absence matrix comprises an identification of whether each of the genome sequences is obtained from an organism resistant to each of a plurality of antibiotics.