Analysis of sequence variants in MALDI mass fingerprints

MALDI mass fingerprinting is routinely used for identification of proteins by matching the masses of tryptic (or other) fragments of the investigated proteins to the predicted fragmentation masses of database proteins. The high probability hits will be to a single protein in a range of species if a good match can be made. The unmatched masses may result from one or more post-translational modifications, point mutations or polymorphisms. In the case of sequence variation, the match may be to a homologous protein in the target organism or in related species. It is straightforward to identify changes due to a single transformation using mutation mass shift tables. However, two or more transformations present a problem because of the large number of possibilities often associated with a single mass difference. We have developed a program that takes the expected and the obtained masses as input and produces a list of all possible single or double transformations within a given mass accuracy. The amino acid composition of the expected fragment can be used to filter the list of transformations. The list is ordered according to the weights of transformations that can be chosen from several models