Sequence analysis of complex amplicons

A method for determining a clonotype profile of T-cell receptors and/or B-cell receptors of an individual, the method comprising the steps of:

• a) obtaining a nucleic acid sample from T-cells and/or B-cells of the individual;
• b) spatially isolating individual molecules derived from such nucleic acid sample, the individual molecules comprising nested sets of templates each generated from a nucleic acid in the sample and each containing a somatically rearranged region or a portion thereof, each nested set comprising a plurality of overlapping templates such that every template of the plurality has a common end and a different end and each nested set being capable of producing a plurality of sequence reads each extending in the same direction and each starting from a different position on the nucleic acid from which the nested set was generated;
• c) bidirectionally sequencing said spatially isolated individual molecules to generate for each nested set a plurality of sequence reads including at least one forward sequence read and at least one reverse sequence read so that at least 1000 clonotypes each having a sequence length of at least 30 nucleotides are determined;
• and
• d) determining abundances of the clonotypes of the different sequences of the nucleic acid molecules from the nucleic acid sample to generate the clonotype profile.