System and method for identification of MicroRNA precursor sequences and corresponding mature MicroRNA sequences from genomic sequences

Abstract

A method for determining microRNA precursors and their corresponding mature microRNAs from genomic sequences is provided. For example, in one aspect of the invention, a method for determining whether a nucleotide sequence contains a microRNA precursor comprises the following steps. Patterns are generated by processing a collection of already known microRNA precursor sequences. One or more attributes are assigned to the generated patterns. Only the patterns whose attributes satisfy certain criteria are subselected, and then the subselected patterns are used to analyze the nucleotide sequence. In another aspect of the invention, a method for identifying a mature microRNA sequence in a microRNA precursor sequence comprises the following steps. One or more patterns are generated by processing a collection of known mature microRNA sequences. The one or more patterns are filtered, and then used to locate instances of the one or more filtered patterns in one or more candidate precursor sequences.

1 . A method for determining whether a nucleotide sequence contains a microRNA precursor, the method comprising the steps of: 
 generating one or more patterns by processing a collection of known microRNA precursor sequences;    assigning one or more attributes to the one or more generated patterns;    subselecting one or more patterns whose one or more attributes satisfy at least one criterion; and    using the one or more subselected patterns to analyze the nucleotide sequence, such that a determination is made whether the nucleotide sequence contains a microRNA precursor.    
   
   
       2 . The method of  claim 1 , wherein the nucleotide sequence is from an intergenic region.  
   
   
       3 . The method of  claim 1 , wherein the nucleotide sequence is from an intronic region.  
   
   
       4 . The method of  claim 1 , wherein the nucleotide sequence is from an amino acid coding region.  
   
   
       5 . The method of  claim 1 , wherein the step of generating one or more patterns comprises using a pattern discovery algorithm.  
   
   
       6 . The method of  claim 5 , wherein the pattern discovery algorithm is the Teiresias pattern discovery algorithm.  
   
   
       7 . The method of  claim 1 , wherein the step of assigning one or more attributes is carried out independently of and prior to the step of using the one or more subselected patterns to analyze a nucleotide sequence.  
   
   
       8 . The method of  claim 1 , wherein the one or more attributes are quantitative.  
   
   
       9 . The method of  claim 8 , wherein at least one of the one or more attributes represents statistical significance.  
   
   
       10 . The method of  claim 8 , wherein at least one of the one or more attributes represents a length of the pattern.  
   
   
       11 . The method of  claim 8 , wherein at least one of the one or more attributes represents a number of positions in the one or more patterns which are not occupied by wild cards.  
   
   
       12 . The method of  claim 8 , wherein a threshold value for each attribute is selected.  
   
   
       13 . The method of  claim 12 , wherein one or more patterns are discarded if the value of the one or more attributes of the pattern is below the selected threshold for the one or more attributes.  
   
   
       14 . The method of  claim 13 , wherein the steps of selecting a threshold value and discarding one or more patterns are repeated for all used attributes.  
   
   
       15 . The method of  claim 1 , wherein a set of counters is created for the nucleotide sequence.  
   
   
       16 . The method of  claim 15 , wherein the counters in the set of counters equal the number of nucleotides in the nucleotide sequence.  
   
   
       17 . The method of  claim 1 , wherein all patterns are examined.  
   
   
       18 . The method of  claim 17 , wherein each pattern with an instance in the nucleotide sequence contributes to the counters at corresponding positions of the nucleotide sequence.  
   
   
       19 . The method of  claim 18 , wherein only consecutive positions in the nucleotide sequences whose corresponding counter values exceed a threshold are considered.  
   
   
       20 . The method of  claim 19 , wherein one or more groups of consecutive positions are considered only if they satisfy a minimum length criterion.  
   
   
       21 . The method of  claim 20 , wherein a secondary structure of each consecutive group of positions is estimated using an RNA secondary structure prediction method.  
   
   
       22 . The method of  claim 21 , wherein the prediction method is one included with software known as the Vienna Package.  
   
   
       23 . The method of  claim 21 , wherein the prediction method is a method called ‘mfold’.  
   
   
       24 . The method of  claim 21 , wherein the predicted structure is assigned one or more attributes.  
   
   
       25 . The method of  claim 24 , wherein at least one of the one or more attributes is folding energy of a formed complex.  
   
   
       26 . The method of  claim 24 , wherein a threshold value for the one or more attributes is selected.  
   
   
       27 . The method of  claim 24 , wherein a complex is discarded if the value of the one or more attributes is below the selected threshold for the one or more attributes.  
   
   
       28 . The method of  claim 27 , wherein the steps of selecting a threshold value and discarding a complex are repeated for all used attributes.  
   
   
       29 . The method of  claim 28 , wherein the nucleotide sequence is reported as a microRNA precursor if the predicted structure that corresponds to the nucleotide sequence has not been discarded.  
   
   
       30 . A system for determining whether a nucleotide sequence contains a microRNA precursor, comprising: 
 a memory that stores computer-readable code; and    a processor operatively coupled to the memory, the processor configured to implement the computer-readable code, the computer-readable code configured to: 
 generate one or more patterns by processing a collection of known microRNA precursor sequences;  
 assign one or more attributes to the one or more generated patterns;  
 subselect the one or more patterns whose one or more attributes satisfy at least one criterion; and  
 use the one or more subselected patterns to analyze the nucleotide sequence, such that a determination is made whether a nucleotide sequence contains a microRNA precursor.  
   
   
   
       31 . An article of manufacture for determining whether a nucleotide sequence contains a microRNA precursor, comprising: 
 a computer-readable medium having computer-readable code embodied thereon, the computer-readable code comprising: 
 a step to generate one or more patterns by processing a collection of known microRNA precursor sequences;  
 a step to assign one or more attributes to the one or more generated patterns;  
 a step to subselect the one or more patterns whose one or more attributes satisfy at least one criterion; and  
 a step to use the one or more subselected patterns to analyze the nucleotide sequence, such that a determination is made whether a nucleotide sequence contains a microRNA precursor.  
   
   
   
       32 . A method for identifying a mature microRNA sequence in a microRNA precursor sequence, comprising the steps of: 
 generating one or more patterns by processing a collection of known mature microRNA sequences;    filtering the one or more patterns; and    locating instances of the one or more filtered patterns in one or more candidate precursor sequences.    
   
   
       33 . A system for identifying a mature microRNA sequence in a microRNA precursor sequence, comprising: 
 a memory that stores computer-readable code; and    a processor operatively coupled to the memory, the processor configured to implement the computer-readable code, the computer-readable code configured to: 
 generate one or more patterns by processing a collection of known mature microRNA sequences;  
 filter the one or more patterns; and  
 locate instances of the one or more filtered patterns in one or more candidate precursor sequences.  
   
   
   
       34 . An article of manufacture for identifying a mature microRNA sequence in a microRNA precursor sequence, comprising: 
 a computer-readable medium having computer-readable code embodied thereon, the computer-readable code comprising: 
 a step to generate one or more patterns by processing a collection of known mature microRNA sequences;  
 a step to filter the one or more patterns; and  
 a step to locate instances of the one or more filtered patterns in one or more candidate precursor sequences.  
   
   
   
       35 . A method for determining whether a nucleotide sequence contains a mature microRNA, the method comprising the steps of: 
 generating one or more patterns by processing a collection of known mature microRNA sequences;    assigning one or more attributes to the one or more generated patterns;    subselecting one or more patterns whose one or more attributes satisfy at least one criterion; and    using the one or more subselected patterns to analyze the nucleotide sequence, such that a determination is made whether the nucleotide sequence contains a mature microRNA.    
   
   
       36 . The method of  claim 35 , wherein the nucleotide sequence is from an intergenic region.  
   
   
       37 . The method of  claim 35 , wherein the nucleotide sequence is from an intronic region.  
   
   
       38 . The method of  claim 35 , wherein the nucleotide sequence is from an amino acid coding region.  
   
   
       39 . The method of  claim 35 , wherein the step of generating one or more patterns comprises using a pattern discovery algorithm.  
   
   
       40 . The method of  claim 39 , wherein the pattern discovery algorithm is the Teiresias pattern discovery algorithm.  
   
   
       41 . The method of  claim 35 , wherein the step of assigning one or more attributes is carried out independently of and prior to the step of using the one or more subselected patterns to analyze a nucleotide sequence.  
   
   
       42 . The method of  claim 35 , wherein the one or more attributes are quantitative.  
   
   
       43 . The method of  claim 42 , wherein at least one of the one or more attributes represents statistical significance.  
   
   
       44 . The method of  claim 42 , wherein at least one of the one or more attributes represents a length of the pattern.  
   
   
       45 . The method of  claim 42 , wherein at least one of the one or more attributes represents a number of positions in the one or more patterns which are not occupied by wild cards.  
   
   
       46 . The method of  claim 42 , wherein a threshold value for each attribute is selected.  
   
   
       47 . The method of  claim 46 , wherein one or more patterns are discarded if the value of the one or more attributes of the pattern is below the selected threshold for the one or more attributes.  
   
   
       48 . The method of  claim 47 , wherein the steps of selecting a threshold value and discarding one or more patterns are repeated for all used attributes.  
   
   
       49 . The method of  claim 35 , wherein a set of counters is created for the nucleotide sequence.  
   
   
       50 . The method of  claim 49 , wherein the counters in the set of counters equal the number of nucleotides in the nucleotide sequence.  
   
   
       51 . The method of  claim 35 , wherein all patterns are examined.  
   
   
       52 . The method of  claim 5   1 , wherein each pattern with an instance in the nucleotide sequence contributes to the counters at the corresponding positions of the nucleotide sequence.  
   
   
       53 . The method of  claim 52 , wherein only consecutive positions in the nucleotide sequences whose corresponding counter values exceed a threshold are considered.  
   
   
       54 . The method of  claim 53 , wherein one or more groups of consecutive positions are considered only if they satisfy a minimum length criterion.  
   
   
       55 . The method of  claim 42 , wherein a threshold value for the one or more attributes is selected.  
   
   
       56 . The method of  claim 55 , wherein a group of consecutive positions is discarded if the value of the one or more attributes is below the selected threshold for the one or more attributes.  
   
   
       57 . The method of  claim 56 , wherein the steps of selecting a threshold value and discarding a group of consecutive positions are repeated for all used attributes.  
   
   
       58 . The method of  claim 57 , wherein the group of consecutive positions that has not been discarded is reported as a mature microRNA.