Techniques for linking non-coding and gene-coding deoxyribonucleic acid sequences and applications thereof

Abstract

Techniques for linking non-coding and gene coding regions of a genome are provided. In one aspect, a method of determining associations between non-coding sequences and gene coding sequences in a genome of an organism comprises the following steps. At least one conserved region is identified from one or more non-coding sequences. Additional instances of the conserved region are located in the untranslated or amino acid coding regions of one or more genes in the organism under consideration, and the conserved region is associated with the one or more biological processes in which these one or more genes participate.

1 . A method of determining associations between non-coding sequences and gene coding sequences in a genome of an organism, the method comprising the steps of: 
 identifying at least one conserved region from a plurality of the non-coding sequences;    linking the at least one conserved region with one or more of the gene coding sequences of the genome; and    associating the at least one conserved region with one or more biological processes of the organism.    
     
     
         2 . The method of  claim 1 , wherein the genome comprises deoxyribonucleic acid.  
     
     
         3 . The method of  claim 1 , wherein the non-coding sequences comprise one or more of intergenic sequences and intronic sequences.  
     
     
         4 . The method of  claim 1 , wherein the step of identifying, further comprises the step of discovering patterns in the non-coding sequences.  
     
     
         5 . The method of  claim 4 , further comprising the step of retaining patterns that have a minimum length and a minimum number of appearances in the non-coding sequences  
     
     
         6 . The method of  claim 5 , wherein the minimum length is sixteen nucleotides.  
     
     
         7 . The method of  claim 5 , wherein the minimum number of appearances is forty.  
     
     
         8 . The method of  claim 4 , further comprising the step of sorting patterns so that longer and more frequent patterns are considered before shorter and less frequent patterns.  
     
     
         9 . The method of  claim 4 , further comprising the step of sorting patterns in order of decreasing value of the product of length-of-pattern and copy-number-of-pattern.  
     
     
         10 . The method of  claim 9 , wherein the patterns are considered in their order of appearance in the sorted list.  
     
     
         11 . The method of  claim 10 , wherein instances of a pattern under consideration are located in the sequences of the region under consideration.  
     
     
         12 . The method of  claim 11 , wherein the region under consideration comprises all 5′ untranslated sequences for the genome under consideration.  
     
     
         13 . The method of  claim 11 , wherein the region under consideration comprises all amino acid coding sequences for the genome under consideration.  
     
     
         14 . The method of  claim 11 , wherein the region under consideration comprises all 3′ untranslated sequences for the genome under consideration.  
     
     
         15 . The method of  claim 11 , wherein a pattern is selected or discarded based on a criterion.  
     
     
         16 . The method of  claim 15 , wherein a pattern is selected if all of its instances occur at positions that do not contain one or more instances of an earlier selected pattern.  
     
     
         17 . The method of  claim 15 , wherein a pattern is discarded if one or more of its instances occur at positions that contain one or more instances of an earlier selected pattern.  
     
     
         18 . The method of  claim 1 , wherein the organism is a eukaryotic organism.  
     
     
         19 . The method of  claim 18 , wherein the eukaryotic organism is one of  H. sapiens, C. familiaris, M. musculus, R. norvegicus, G. gallus, D. melanogaster  and  C. elegans.    
     
     
         20 . The method of  claim 1 , wherein the identifying step further comprises the step of discovering patterns in the non-coding sequences and the linking step further comprises the step of searching for instances of the discovered patterns in the genome associated with one or more of the untranslated or amino acid coding sequences of the genes in the organism under consideration.  
     
     
         21 . The method of  claim 1 , further comprising the step of: 
 linking each identified pattern with the one or more biological processes that are associated with the one or more genes whose untranslated and amino acid coding regions contain one or more instances of the pattern.    
     
     
         22 . An apparatus for determining associations between non-coding sequences and gene coding sequences in a genome of an organism, the apparatus comprising: 
 a memory; and    at least one processor, coupled to the memory, operative to: 
 identify at least one conserved region from a plurality of the non-coding sequences;  
 link the at least one conserved region with one or more of the gene coding sequences of the genome; and  
 associating the at least one conserved region with one or more biological processes of the organism.  
   
     
     
         23 . An article of manufacture for determining associations between non-coding sequences and gene coding sequences in a genome of an organism, comprising a machine readable medium containing one or more programs which when executed implement the steps of: 
 identifying at least one conserved region from a plurality of the non-coding sequences;    linking the at least one conserved region with one or more of the gene coding sequences of the genome; and    associating the at least one conserved region with one or more biological processes of the organism.    
     
     
         24 . A method of designing one or more sequences of short interfering RNAs that can interact with one or more sites in a given transcript of a given sequence in a given organism and result in the down-regulation of the expression of a protein product encoded by the given transcript, the method comprising the steps of: 
 identifying one or regions of interest in the sequence of the given transcript;    sub-selecting one or more regions from the collection of the regions of interest;    generating one or more derived sequences from the sequence of the one or more sub-selected regions;    using the one or more derived sequences to create one or more instances of a corresponding molecule that the one or more derived sequences represent; and    using the one or more instances of the created molecule in an appropriate environment to regulate the expression of the given transcript.    
     
     
         25 . The method of  claim 24 , wherein a region of interest in the collection of regions of interest is identified to be an instance of a motif that has one or more copies in intergenic and intronic regions of the genome of interest and one or more copies in untranslated and amino acid coding regions of one or more genes in the genome of interest.  
     
     
         26 . The method of  claim 24 , wherein a region of interest in the collection of regions of interest is identified using a method that is based on pattern discovery.  
     
     
         27 . The method of  claim 24 , wherein a region of interest in the collection of regions of interest is identified to be a target island.  
     
     
         28 . The method of  claim 24 , wherein a region of interest is located in a 5′ untranslated region of the given transcript.  
     
     
         29 . The method of  claim 24 , wherein a region of interest is located in an amino acid coding region of the given transcript.  
     
     
         30 . The method of  claim 29 , wherein a region of interest is located in a 3′ untranslated region of the given transcript.  
     
     
         31 . The method of  claim 24 , wherein the genome of interest is a eukaryotic genome.  
     
     
         32 . The method of  claim 31 , where the eukaryotic genome is a human genome.  
     
     
         33 . The method of  claim 31 , wherein the eukaryotic genome is a mouse genome.  
     
     
         34 . The method of  claim 31 , wherein the eukaryotic genome is a rat genome.  
     
     
         35 . The method of  claim 31 , wherein the eukaryotic genome is a dog genome.  
     
     
         36 . The method of  claim 31 , wherein the eukaryotic genome is a fruit fly genome.  
     
     
         37 . The method of  claim 31 , wherein the eukaryotic genome is a worm genome.  
     
     
         38 . The method of  claim 24 , wherein a region of interest is sub-selected based on one or more of its attributes.  
     
     
         39 . The method of  claim 38 , wherein an attribute is length of the region.  
     
     
         40 . The method of  claim 38 , wherein an attribute is location of the region in the transcript.  
     
     
         41 . The method of  claim 24 , wherein a derived sequence is a reverse complement of the sequence of the one or more sub-selected regions.  
     
     
         42 . The method of  claim 24 , wherein a derived sequence is a near-reverse complement of the sequence of the one or more sub-selected regions.  
     
     
         43 . The method of  claim 24 , wherein the one or more copies of the molecule can be built using any of a set of biochemical processes.  
     
     
         44 . A method of engineering a given transcript of a given gene in a given organism in order to regulate its expression, the method comprising the steps of: 
 identifying one or more regions of interest in a sequence of the given transcript;    sub-selecting one or more regions from the collection of the regions of interest; and    using the one or more sub-selected regions to make one or more modifications to the sequence of the given transcript.    
     
     
         45 . The method of  claim 44 , wherein a region of interest in the collection of regions of interest comprises an instance of a motif that has one or more copies in intergenic and intronic regions of the genome of interest and one or more copies in untranslated and amino acid coding regions of one or more genes in the genome of interest.  
     
     
         46 . The method of  claim 45 , where the motif is computed using a process wherein associations are determined between non-coding sequences and gene coding sequences in a genome of an organism, the process comprising the steps of: 
 identifying at least one conserved region from a plurality of the non-coding sequences;    linking the at least one conserved region with one or more of the gene coding sequences of the genome; and    associating the at least one conserved region with one or more biological processes of the organism.    
     
     
         47 . The method of  claim 44 , wherein a region of interest in the collection of regions of interest is computed using a method that is based on pattern discovery.  
     
     
         48 . The method of  claim 44 , wherein a region of interest is located in a 5′ untranslated region of the given transcript.  
     
     
         49 . The method of  claim 44 , wherein a region of interest is located in an amino acid coding region of the given transcript.  
     
     
         50 . The method of  claim 44 , wherein a region of interest is located in a 3′ untranslated region of the given transcript.  
     
     
         51 . The method of  claim 44 , wherein a region of interest is sub-selected based on one or more of its attributes.  
     
     
         52 . The method of  claim 51 , wherein an attribute is length of the region.  
     
     
         53 . The method of  claim 51 , wherein an attribute is location of the region in the transcript.  
     
     
         54 . The method of  claim 51 , wherein an attribute is association of the region with a given biological process.  
     
     
         55 . The method of  claim 51 , wherein an attribute is association of the region with a given tissue.  
     
     
         56 . The method of  claim 51 , wherein an attribute is association of the region with a given cellular compartment.  
     
     
         57 . The method of  claim 44 , wherein a modification comprises an extension of the sequence of the given transcript.  
     
     
         58 . The method of  claim 57 , wherein the extension comprises one or more instances of a region of interest.  
     
     
         59 . The method of  claim 44 , wherein a modification comprises a shortening of the sequence of the given transcript.  
     
     
         60 . The method of  claim 59 , wherein the shortening comprises one or more instances of a region of interest.