Patent ID: 7756644

Claim:
A computer-assisted method for identifying T-cell epitopes of a target protein that are likely to bind to an MHC class I allele of interest comprising: a) selecting an MHC allele of interest; b) collecting and curating a training set which comprises peptide sequences which are known to bind to the MHC allele, wherein the peptide sequences consist of 9 amino acid positions (9mers) or 10 amino acid positions (10mers); c) grouping the peptide sequences in the training set into clusters based on a predetermined amino acid sequence identity threshold; d) determining an empirical binding score matrix (ESM) which summarizes the fraction of clusters that contain each of 20 amino acids at each of the 9 or 10 positions of the peptide sequences in the training set; wherein the values of the ESM (F) are calculated: (i) F(i,j)=n(i,j)/N j for flanking positions, j, wherein flanking positions are positions 1-4 and 6-9 for 9mers and positions 1-4 and 7-10 for 10mers, and (ii) F(i,j)=½(number of 9mer clusters containing i at position 5/total number of clusters of 9mers)+((number of 10mer clusters containing i at positions 5 or 6)/(total number of clusters of 10mers)) for central positions, j, wherein central positions are position 5 for 9mers and positions 5 and 6 for 10mers, wherein n(i,j) is the number of clusters containing amino acid i at position j and N j =Σ i n(i,j); e) calculating a Bayes-corrected scoring matrix (BSM) from the ESM, wherein the values of the BSM (B) are calculated B(i,j)=log [{(F(i,j)/S i )+(e/N j )}/{1+(e/N j )}] wherein S i is the frequency of occurrence of amino acid i in a protein database; f) using the BSM to calculate a predicted binding score for a test series of candidate T-cell epitopes derived from the target protein, wherein the candidate T-cell epitopes consist of 9 or 10 amino acids, wherein the predicted binding score (S) is calculated: (i) for each 9mer (a 1 . . . a 9 ), S=Σ i B(a i ,i), and (ii) for each 10mer (a 1 . . . a 10 ), S=Σ i=1,2,3,4 B(a i ,i)+Σ i =Σ i=7,8,9,10 B(a i ,i)+½{B(a 5 ,5)+B(a 6 ,6)}; wherein steps d) through g) are carried out using a computer processor; g) identifying T-cell epitopes of the target protein that are likely to bind to the MHC allele of interest, wherein the candidate T-cell epitopes of the test series having a binding score that is equal to or greater than a predetermined threshold when compared to the binding score of all other candidate T-cell epitopes in the test series are identified as T-cell epitopes likely to bind to the MHC class I allele of interest, wherein the predetermined threshold is based on a percentile at which a fraction of randomly generated peptides have a lower binding score; h) outputting the result of at least one of steps g) and h) to at least one of a data storage system and an output device.