Sequence assembly

1. A method for identifying a mutation in a nucleic acid, the method comprising:

sequencing nucleic acid to generate a plurality of sequence reads;

creating a contig based on the reads;

aligning the contig to a reference sequence;

aligning the individual reads back to the contig; and

identifying a mutation based on the alignments to the contig and the reference sequence.

2. The method of claim 1 , further comprising splitting the reads into subsets corresponding to known locations.

3. The method of claim 1 , further comprising identifying a mutation in the contig relative to the reference.

4. The method of claim 1 further comprising determining a position of the mutation in the nucleic acid based on a position of the mutation in the reads and the alignments to the contig and the reference sequence.

5. The method of claim 1 wherein the mutation is selected from the group consisting of: a single nucleotide polymorphism (SNP), an insertion, a deletion, a substitution, a translocation, an epigenetic mutation, and a copy number repeat.

6. The method of claim 1 wherein a plurality of mutations are identified.

7. The method of claim 6 wherein a first mutation is within about 100 nucleotides of a second mutation.

8. The method according to claim 7 , wherein the first mutation is a substitution and the second mutation is a deletion.

9. The method of claim 1 wherein the mutation is a deletion at an end of a sequence read.

10. The method of claim 1 , wherein the mutation is associated with a disease.

11. The method according to claim 1 , wherein sequencing is sequencing-by-synthesis.

12. The method according to claim 11 , wherein sequencing-by-synthesis is single molecule sequencing-by-synthesis.