Tag reagent and assay method

A method of sequencing a target nucleic acid, which method comprises the steps of:

• a) providing an oligonucleotide immobilized on a support,
• b) hybridizing the target nucleic acid with the immobilized oligonucleotide,
• c) incubating the hybrid from b) with a library comprising a solution of reagents, each of said reagents comprising
• 1) an analyte moiety comprising at least two analyte residues, and linked to
• 2) a tag moiety comprising one or more reporter groups suitable for detection by mass spectrometry, excluding oligonucleotides.
• wherein a reporter group designates an analyte residue, and the reporter group at each position of the tag moiety is chosen to designate an analyte residue at a defined position of the analyte moiety
• and wherein the library consists of 4.sup.n reagents, each of said reagents comprising a different analyte moiety which is a different oligonucleotide chain of n nucleotides,
• so that an oligonucleotide chain of a first reagent of the library becomes hybridized to the target nucleic acid adjacent the immobilized oligonucleotide,
• d) ligating the adjacent oligonucleotides, thus forming a ligated first reagent,
• e) removing other non-ligated reagents, and
• f) recovering and analyzing the tag moiety of the ligated first reagent as an indication of the sequence of a first part of the target nucleic acid wherein the said target nucleic acid and ligated first reagent remain hybridized.