Patent ID: 7820378

Claim:
A method for determining the sequence of one or more sequence variations in a target nucleic acid relative to a reference sequence, comprising: (a) generating mass signals for target nucleic acid fragments by mass spectrometry, wherein the target nucleic acid fragments result from a specific cleavage reaction of the target nucleic acid; (b) generating or simulating mass signals for reference fragments, wherein the reference fragments result from cleavage or simulated cleavage of the reference sequence using the same specific cleavage reaction in (a); (c) identifying mass signals in the target nucleic acid fragment spectrum that are different relative to the reference fragment spectrum, thereby identifying different target nucleic acid fragments; (d) generating one or more compomer witnesses corresponding to each different target nucleic acid fragment identified in (c); (e) selecting, from the set of all possible subsequences of the reference sequence, a subset of subsequences having at most k cleavage points for the specific cleavage reaction, wherein k is user-defined; (f) generating for each compomer witness in (d) all possible sequence variations of one or more subsequences in the subset selected in (e) that would lead to the compomer witness, thereby identifying a reduced set of candidate sequence variations; and (g) scoring the candidate sequence variations identified in (f) to determine the sequence of the one or more sequence variations in the target nucleic acid.