Briefly, the 454 pyrosequencing system shears the source genetic material into fragments of approximately 300-800 bases. Millions of single-stranded fragments are sequenced by synthesizing their complementary strands. Repeatedly, nucleotide reagents are flown over the fragments, one nucleotide (A, C, T, or G) at a time. Light is emitted at a fragment location when the flown nucleotide base complements the first unpaired base of the fragment [13, 14] . Multiple identical nucleotides may be incorporated in a single cycle, in which case the light intensity corresponds to the number of incorporated bases. However, since the number of incorporated bases (referred to as a homopolymer length) cannot be estimated accurately for long homopolymers, it results in a relatively high percentage of insertion and deletion sequencing errors (which respectively represent 65%-75% and 20%-30% of all sequencing errors [15, 16] ).