SYSTEM AND METHODS FOR INDEL IDENTIFICATION USING SHORT READ SEQUENCING

1 . (canceled)

2 . The method of claim 22 , 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 a 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 22 , 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 .- 20 . (canceled)

21 . A method of nucleic acid sequence analysis, comprising:

sequencing a first locality from a plurality of nucleic acid fragments to generate first non-overlapping sequences of a plurality of mate pair sequences;

sequencing a second locality from the nucleic acid fragments to generate second non-overlapping sequences of the mate pair sequences, the first and second locality of a nucleic acid fragment corresponds to a first region of a genome and a second region of a genome, the first and second regions separated by an intervening region whose length is within a known range;

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

performing a computer assisted mapping operation for the mate pair sequences in which the first non-overlapping pairwise sequence and the second non-overlapping pairwise sequence for a respective mate pair are aligned to the at least one reference sequence using a processor by the steps of:

performing a first mapping operation using a processor to align the first non-overlapping pairwise sequence of the mate pair sequences to the at least one reference sequence with a first selected mismatch constraint,

identifying mate pair sequences having first non-overlapping pairwise sequences which are aligned to the at least one reference sequence while satisfying the selected mismatch constraint,

designating a window region within the at least one reference sequence for the identified mate pair sequences based on the alignment of the first non-overlapping pairwise sequence to the at least one reference sequence,

performing a second mapping operation using a processor to align the second non-overlapping pairwise sequence to the window region of the reference sequence with a second selected mismatch constraint,

identifying mate pair sequences with first and second non-overlapping pairwise sequences that have mapped to the at least one reference sequence following performing the first and second mapping operations;

and,

outputting the results of the mapping operations.

22 . A method for nucleic acid sequence analysis, comprising:

sequencing a first locality and a second locality from at least one nucleic acid fragment to generate first and second non-overlapping sequences, the first locality corresponding to a first region of a genome and the second locality corresponding to a second region of a genome, the first and second regions separated by an intervening region;

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

performing a first mapping operation 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.

23 . A method for nucleic acid sequence analysis, comprising:

sequencing at least a portion of a plurality nucleic acid fragments to generate 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.

24 . The method of claim 23 , 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.

25 . The method of claim 23 , wherein overlapping reads are determined by a match of a minimum number of bases of an overlap region between reads.