Method and System for the Use of Biomarkers for Regulatory Dysfunction in Disease

Abstract

Measuring of the binding of a transcription factor (using, for example, chromatin immunoprecipitation) according to the present invention is provides an improved marker for a disease. These markers can be used in diagnostics for diseases where a transcription factor binding event plays a role. Additionally, they can be used to adjust disease risk profiles for healthy individuals as with typical genetic variants.

1 - 20 . (canceled) 
     
     
         21 . A method for treating a person for a genetic disease, comprising:
 obtaining genetic data from an individual, wherein the genetic data identifies a set of genetic variants from the individual;   obtaining non-coding region data, wherein the non-coding region data includes:
 a set of genes, 
 a set of non-coding regions, wherein each of the non-coding regions in the set of non-coding regions is associated with at least one gene from the set of genes and forms an interaction with a trans-element, wherein the trans-element is selected from the group consisting of a protein and a nucleic acid, wherein the interaction affects gene expression of the at least one gene, and 
 a set of interaction altering variants, wherein each of the interaction altering variants in the set of interaction altering variants is located in a corresponding non-coding region in the set of non-coding regions, alters the interaction formed by the non-coding region, and is associated with an altered gene expression of the at least one gene associated with the non-coding region; 
   obtaining clinical information for the set of non-coding regions, wherein the clinical information includes a clinical relevance of the at least one gene associated with each non-coding region and a disease associated with the altered gene expression of the at least one gene associated with each non-coding region;   identifying a candidate gene and an associated altered gene expression of the candidate gene from the non-coding region data by matching a particular genetic variant from the set of genetic variants from the individual to an interaction altering variant from the set of interaction altering variants, wherein the matched particular variant is located in a particular non-coding region associated with the candidate gene;   identifying a particular clinical relevance of the candidate gene and a particular disease associated with the associated altered gene expression of the associated candidate gene for the candidate genetic variant from the clinical information; and   taking clinical action by treating the patient for the particular disease based on the particular clinical relevance of the candidate gene.   
     
     
         22 . The method of  claim 21 , wherein the genetic variant data is obtained by genome sequencing. 
     
     
         23 . The method of  claim 21 , wherein the set of non-coding regions includes elements selected from the group consisting of: transcription factor binding sites, promoter regions, 5′-UTRs, nucleosome positions, DNase I hypersensitive sites, regions of DNA methylation, intronic nucleotides, 3′-UTRs, intergenic regions, conserved non-coding elements, insulators, silencers, and enhancers. 
     
     
         24 . The method of  claim 21 , wherein the interaction formed by each of the non-coding regions in the set of non-coding regions is measured by at least one of the group consisting of: chromatin-immunoprecipitation and electrophoretic mobility shift. 
     
     
         25 . The method of  claim 21 , wherein the interaction formed by each of the non-coding regions in the set of non-coding regions is measured by chromatin-immunoprecipitation on at least one chromatin sample. 
     
     
         26 . The method of  claim 25 , wherein the chromatin-immunoprecipitation is selected from the group consisting of: reversibly cross-linked chromatin-immunoprecipitation and native chromatin-immunoprecipitation. 
     
     
         27 . The method of  claim 21 , wherein the obtaining non-coding region data step comprises the steps of:
 accessing a database of published literature, wherein each piece of published literature is a full-text document and contains an abstract;   obtaining a set of full-text documents from the database of published literature, wherein the abstract of each full-text document in the set of full-text documents contains at least one gene identifier and at least one type of regulatory element; and   filtering the set of full-text documents by querying each document in the set of full-text documents for word stems indicating studies to assess binding activity and an effect on gene activity.   
     
     
         28 . The method of  claim 27 , wherein the obtaining a full-text documents comprises the steps of:
 querying the abstracts of the published literature in the database of published literature for the at least one gene identifier and the at least one type of regulatory element; and   downloading the set of full-text documents from the database of published literature.   
     
     
         29 . The method of  claim 27 , further comprising the step of converting the set of full-text documents into plain text. 
     
     
         30 . The method of  claim 27 , wherein the obtaining genetic annotations step comprises the step of generating the genetic annotations by querying the set of full-text documents for terms relating to at least one disease. 
     
     
         31 . A computer-readable medium including instructions that, when executed by a processing unit, cause the processing unit to implement a method for analyzing genetic variants, by performing the steps of:
 obtaining genetic data from an individual, wherein the genetic data identifies a set of genetic variants from the individual;   obtaining non-coding region data, wherein the non-coding region data includes:
 a set of genes, 
 a set of non-coding regions, wherein each of the non-coding regions in the set of non-coding regions is associated with at least one gene from the set of genes and forms an interaction with a trans-element, wherein the trans-element is selected from the group consisting of a protein and a nucleic acid, wherein the interaction affects gene expression of the at least one gene, and 
 a set of interaction altering variants, wherein each of the interaction altering variants in the set of interaction altering variants is located in a corresponding non-coding region in the set of non-coding regions, alters the interaction formed by the non-coding region, and is associated with an altered gene expression of the at least one gene associated with the non-coding region; 
   obtaining clinical information for the set of non-coding regions, wherein the clinical information includes a clinical relevance of the at least one gene associated with each non-coding region and a disease associated with the altered gene expression of the at least one gene associated with each non-coding region;   identifying a candidate gene and an associated altered gene expression of the candidate gene from the non-coding region data by matching a particular genetic variant from the set of genetic variants from the individual to an interaction altering variant from the set of interaction altering variants, wherein the matched particular variant is located in a particular non-coding region associated with the candidate gene;   identifying a particular clinical relevance of the candidate gene and a particular disease associated with the associated altered gene expression of the associated candidate gene for the candidate genetic variant from the clinical information; and   taking clinical action by treating the patient for the particular disease based on the particular clinical relevance of the candidate gene.   
     
     
         32 . The method of  claim 31 , wherein the genetic variant data is obtained by genome sequencing. 
     
     
         33 . The method of  claim 31 , wherein the set of non-coding regions includes elements selected from the group consisting of: transcription factor binding sites, promoter regions, 5′-UTRs, nucleosome positions, DNase I hypersensitive sites, regions of DNA methylation, intronic nucleotides, 3′-UTRs, intergenic regions, conserved non-coding elements, insulators, silencers, and enhancers. 
     
     
         34 . The method of  claim 31 , wherein the interaction formed by each of the non-coding regions in the set of non-coding regions is measured by at least one of the group consisting of: chromatin-immunoprecipitation and electrophoretic mobility shift. 
     
     
         35 . The method of  claim 31 , wherein the interaction formed by each of the non-coding regions in the set of non-coding regions is measured by chromatin-immunoprecipitation on at least one chromatin sample. 
     
     
         36 . The method of  claim 35 , wherein the chromatin-immunoprecipitation is selected from the group consisting of: reversibly cross-linked chromatin-immunoprecipitation and native chromatin-immunoprecipitation. 
     
     
         37 . The method of  claim 31 , wherein the obtaining DNA-protein binding data step comprises the steps of:
 accessing a database of published literature, wherein each piece of published literature is a full-text document and contains an abstract;   obtaining a set of full-text documents from the database of published literature, wherein the abstract of each full-text document in the set of full-text documents contains at least one gene identifier and at least one type of regulatory element; and   filtering the set of full-text documents by querying each document in the set of full-text documents for word stems indicating studies to assess binding activity and an effect on gene activity.   
     
     
         38 . The method of  claim 37 , wherein the obtaining a full-text documents comprises the steps of:
 querying the abstracts of the published literature in the database of published literature for the at least one gene identifier and the at least one type of regulatory element; and   downloading the set of full-text documents from the database of published literature.   
     
     
         39 . The method of  claim 37 , further comprising the step of converting the set of full-text documents into plain text. 
     
     
         40 . The method of  claim 37 , wherein the obtaining genetic annotations step comprises the step of generating the genetic annotations by querying the set of full-text documents for terms relating to at least one disease.