De-novo sequencing of nucleic acids

A method for the sequencing of a target nucleic acid comprising:

• a) performing a multistage mass spectrometry, comprising
• i) ionizing said target nucleic acid,
• ii) measuring the mass of the ionized target nucleic acid,
• iii) determining the base composition corresponding to the mass of said ionized target nucleic acid,
• iv) fragmenting said ionized target nucleic acid by a collision induced dissociation (CID) and
• v) measuring the corresponding mass spectrum of the CID fragments, and
• b) comparing the measured CID mass spectrum of the target nucleic acid measured in step v) with a plurality of calculated CID mass spectra, wherein each of said calculated CID mass spectra correspond to a base sequence having the base composition determined in step iii),
• wherein the comparison of the measured CID mass spectrum with the calculated CID mass spectra is performed by an optimization algorithm,
• wherein said optimization algorithm compares said measured CID mass spectrum successively with said plurality of calculated CID mass spectra and determines a respective score value for each comparison, said score value representing the degree of consistency between said measured CID mass spectrum and said calculated CID mass spectra, and
• wherein the base sequence corresponding to the calculated CID mass spectra yielding the best score value is selected as the base sequence of said target nucleic acid.