Method and apparatus for determining consensus secondary structures for nucleic acid sequences

A method for identifying consensus secondary structures for a plurality of nucleic acid sequences having a select functional relatedness comprising the steps of:

• a) aligning the plurality of oligonucleotide sequences according to primary structure similarity;
• b) providing a computer system including a central processing unit, associated memory and a visual display;
• c) inputting into the associated memory the plurality of oligonucleotide sequences;
• d) computing using the central processing unit a matrix using the following equation:
• M.sub.ij =1/N .SIGMA..sub.n .SIGMA..sub.b:b' C(b:b).delta.(a.sub.n,i -b).delta.(a.sub.nj -b')
• where M.sub.ij is the relative strength of base paring between nucleotides at a position i and a position j of the matrix, a.sub.n,i designates a nucleotide at a position i of a sequence n in an N-sequence multiple alignment, b:b' indicate one of the four Watson-Crick or two G:U base pairs, C(b:b') is a select general coefficient and .delta.(a.sub.n,i -b) is the Kronecker delta function, which is equal to 1 if a.sub.n,i =b, and is otherwise equal to 0;
• e) visually displaying the matrix, thereby displaying all possible secondary structures of the aligned sequences;
• and
• f) identifying relatively high-strength consensus structures.

A method for identifying consensus secondary structures for a plurality of nucleic acid sequences having a select functional relatedness comprising the steps of:

• a) aligning the plurality of oligonucleotide sequences according to primary structure similarity;
• b) providing a computer system including a central processing unit, associated memory and a visual display;
• c) inputting into the associated memory the plurality of oligonucleotide sequences;
• d) computing using the central processing unit a matrix computed using the following equation:
• M.sub.ij =1/2(.SIGMA..sub.b:b' f.sub.bi,b'j log.sub.2 ›f.sub.bi,b'j /f.sub.bi f.sub.b'j !)
• where
• f.sub.bi =1/N.SIGMA..sub.n .delta.(a.sub.n,i -b),
• f.sub.bi,b'j =1/N.SIGMA..sub.n .delta.(a.sub.n,i -b) .delta.(a.sub.n,j -b') ,
• f.sub.bi is the fraction of sequences which have a base b at position i in the multiple alignment, and f.sub.bi, b'j is the fraction of sequences which form a b:b' base pair at positions i and j;
• e) visually displaying the matrix, thereby displaying all possible secondary structures of the aligned sequences;
• and
• f) identifying relatively high-strength consensus stem structures.

A system for identifying consensus secondary structures for a plurality of nucleic acid sequences having a select functional relatedness comprising:

• input means for inputting into an associated memory a plurality of functionally related oligonucleotide sequences aligned according to primary structure similarity;
• a central processing unit coupled to the associated memory;
• a display coupled to the central processing unit;
• the central processing unit being preprogrammed to compute from the inputted oligonucleotide sequences a matrix representing the strength of a select property determinant of consensus stem structure between nucleotides of each aligned oligonucleotide sequence;
• the central processing unit further being programmed to identify consensus structures of a select strength from the computed matrix;
• the central processing unit outputting to the display the consensus structures of the select strength and all possible secondary structures of the aligned sequences.

A computer-readable storage medium containing computer readable instructions that when executed by a computer connected to a display, performs the steps comprising:

• retrieving from a memory coupled to the computer a data set comprising a select plurality of aligned functionally related oligonucleotide sequences;
• selectively calculating one of a Watson-Crick base pair matrix, a covariation matrix and a G-Quartet matrix;
• and
• outputting on the display the calculated matrix, the matrix showing all possible secondary structures of the aligned sequences.