Helicos has developed its own dynamic programming alignment tools optimized for sequences output from the HeliScope™ Single Molecule Sequencer. These non-proprietary tools, which will be made available through Helicos’ open source portal, will enable alignment of the full length of a short sequence fragment (25- to 30-mer) to a long reference sequence without incurring end gap penalties.

For flexibility, Helicos’ alignment tools support three methods of alignment:

• Needleman-Wunsch
• Smith-Waterman
• A “hybrid” type combining features of global and local alignment schemes

Multi-Pass Sequencing Alignment

The Helicos method developed for multi-pass sequencing mode involves:

•  Alignment of the reads to each other to form a consensus;
• Alignment of the consensus to the reference sequence to identify candidate sub-regions of the genome where alignment is likely;
• Decoupling of the individual reads;
• Alignment of the individual reads to the best candidate sub-region;
• Application of a scoring function to select the best alignment.