System and methods for indel identification using short read sequencing

1. A computer implemented method for nucleic acid sequence analysis, comprising:

receiving sample nucleic acid sequence information comprising one or more mate pair sequences, wherein mate pair sequences comprise a first non-overlapping sequence and a second non-overlapping sequence separated by an intervening sequence;

receiving a reference nucleic acid sequence information comprising at least one reference sequence;

performing a first mapping operation for the sample nucleic acid sequence information using a processor to at least partially align the first non-overlapping sequence to the reference nucleic acid sequence,

designating a window region comprising at least a portion of the at least one reference sequence based at least in part upon the alignment of the first non-overlapping sequence to the at least one reference sequence,

performing a second mapping operation using a processor to at least partially align the second non-overlapping sequence to the designated window region of the reference sequence thereby positioning the first and second non-overlapping sequences with respect to one another, and

outputting the results of the mapping operations.

2. The method of claim 1 , wherein the second mapping operation further identifies indels with respect to the reference sequence by determining a difference between an expected intervening sequence length between the non-overlapping sequences of a mate pair and an observed intervening sequence length between the non-overlapping sequences of the mate pair.

3. The method of claim 2 , wherein the indel comprises an insertion occurring between the non-overlapping sequences of a mate pair which accounts for the difference between the expected intervening sequence length and the observed intervening sequence length.

4. The method of claim 2 , wherein the indel comprises a deletion occurring between the non-overlapping sequences of a mate pair which accounts for the difference between the expected intervening sequence length and the observed intervening sequence length.

5. The method of claim 1 , wherein the first nucleic acid sequence information comprises paired read sequence information separated by the intervening sequence whose length is within a known range.

6. The method of claim 5 , wherein each of the paired read sequences has a length of between approximately 10 and 75 bases.

7. The method of claim 5 , wherein the intervening sequence has a length of between approximately 2 kilobases and 15 kilobases.

8. A computer implemented method for nucleic acid sequence analysis, comprising:

receiving sample nucleic acid sequence information comprising a plurality of sequence reads;

receiving a reference nucleic acid sequence information comprising at least one reference sequence;

mapping the plurality of sequence reads using a processor to at least partially align the sequence reads to the reference nucleic acid sequence;

identifying a first sequence read that partially maps to a first portion of the reference nucleic acid sequence and second sequence read that partially maps to a second portion of the reference nucleic acid sequence;

traversing a shortest path along overlapping sequence reads using a processor to determine a sequence of an indel between the first portion of the reference nucleic acid sequence and the second portion of the reference nucleic acid sequence; and

outputting the sequence of the indel.

9. The method of claim 8 , further comprising identifying overlapping sequence reads comprising a sequence read that partially overlaps with the first sequence read and sequence read that overlaps the second sequence read.

10. The method of claim 8 , wherein overlapping reads are determined by a match of a minimum number of bases of an overlap region between reads.