# US 2008/0189049 A1 · System and methods for indel identification using short read sequencing > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2008/0189049 A1 - Document ID: US20080189049A1 - Status: Published application - Kind: A1 - Application number: 12/026,477 - Filed: 2008-02-05 - Published: 2008-08-07 - Earliest claimed: 2007-02-05 - Assignees: Applera Corporation - Inventors: Zheng ZHANG - Web page: https://patentgrep.com/patent/US20080189049A1 ## CPC - G16B 30/20: Sequence assembly - G16B 30/00: ICT specially adapted for sequence analysis involving nucleotides or amino acids - G16B 30/10: Sequence alignment; Homology search - G16B: BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY ## Abstract Systems, methods, and analytical approaches for short read sequence assembly and for the detection of insertions and deletions (indels) in a reference genome. A method suitable for software implementation is presented in which indels may be readily identified in a computationally efficient manner. ## Claims ### Claim 1 A method of nucleic acid sequence analysis, comprising: receiving nucleic acid sequence information comprising one or more mate pair sequences, wherein mate pair sequences comprise non-overlapping pairwise sequences separated by an intervening sequence length; receiving nucleic acid sequence information comprising at least one reference sequence; performing a mapping operation for each of the one or more mate pair sequences in which the non-overlapping pairwise sequences are aligned to the at least one reference sequence by the steps of: performing a first mapping operation aligning the non-overlapping pairwise sequences to the at least one reference sequence with a selected mismatch constraint identifying non-overlapping pairwise sequences for which one of the non-overlapping pairwise sequences align to the at least one reference sequence while satisfying the selected mismatch constraint; performing a second mapping operation designating a window region of the reference sequence to align the non aligned pairwise sequence with a selected mismatch constraint; identifying non-overlapping pairwise sequences that are successfully mapped following performing the first and second mapping operations; and, outputting the results of the mapping operations. ### Claim 2 (depends on 1) 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 pairwise sequences and an observed intervening sequence length between the non-overlapping pairwise sequences. ### Claim 3 (depends on 2) The method of claim 2, wherein the indel comprises an insertion occurring between the non-overlapping pairwise sequences which accounts for the difference between the expected intervening sequence length and the observed intervening sequence length. ### Claim 4 (depends on 2) The method of claim 2, wherein the indel comprises a deletion occurring between the non-overlapping pairwise sequences which accounts for the difference between the expected intervening sequence length and the observed intervening sequence length. ### Claim 5 (depends on 1) The method of claim 1, wherein the non-overlapping sequence information comprises paired read sequence information separated by the intervening sequence whose distance is approximately known. ### Claim 6 (depends on 5) The method of claim 5, wherein each of the paired read sequences has a length of between approximately 10 and 75 bases. ### Claim 7 (depends on 5) The method of claim 5, wherein the intervening sequence has a length of between approximately 2 kilobases and 15 kilobases. ### Claim 8 A system for nucleic acid sequence analysis, comprising: a data analysis unit configured to: receive nucleic acid sequence information for one or more mate pair sequences, wherein mate pair sequences comprise non-overlapping pairwise sequences separated by an intervening sequence length and further configured to receive nucleic acid sequence information for at least one reference sequence; perform a mapping operation for each of the one or more mate pair sequences in which the non-overlapping pairwise sequences are aligned to the at least one reference sequence by the steps of: performing a first mapping operation aligning the non-overlapping pairwise sequences to the at least one reference sequence with a selected mismatch constraint identifying non-overlapping pairwise sequences for which one of the non-overlapping pairwise sequences align to the at least one reference sequence while satisfying the selected mismatch constraint; performing a second mapping operation designating a window region of the reference sequence to align the non aligned pairwise sequence with a selected mismatch constraint; identify non-overlapping pairwise sequences that are successfully mapped following performing the first and second mapping operations; and, a data terminal for displaying the results of the mapping operations generated by the data analysis unit to a user. ### Claim 9 (depends on 8) The system of claim 8, wherein the second mapping operation performed by the data analysis unit further identifies indels with respect to the reference sequence by determining a difference between an expected intervening sequence length between the non-overlapping pairwise sequences and an observed intervening sequence length between the non-overlapping pairwise sequences. ### Claim 10 (depends on 9) The system of claim 9, wherein the indel comprises an insertion occurring between the non-overlapping pairwise sequences which accounts for the difference between the expected intervening sequence length and the observed intervening sequence length. ### Claim 11 (depends on 9) The system of claim 9, wherein the indel comprises a deletion occurring between the non-overlapping pairwise sequences which accounts for the difference between the expected intervening sequence length and the observed intervening sequence length. ### Claim 12 (depends on 8) The system of claim 8, wherein the non-overlapping sequence information comprises paired read sequence information separated by the intervening sequence whose distance is approximately known. ### Claim 13 (depends on 12) The system of claim 12, wherein each of the paired read sequences has a length of between approximately 10 and 75 bases. ### Claim 14 A computer-readable medium, the computer-readable medium being readable to execute a method of nucleic acid sequence analysis, the method comprising: receiving nucleic acid sequence information comprising one or more mate pair sequences, wherein mate pair sequences comprise non-overlapping pairwise sequences separated by an intervening sequence length; receiving nucleic acid sequence information comprising at least one reference sequence; performing a mapping operation for each of the one or more mate pair sequences in which the non-overlapping pairwise sequences are aligned to the at least one reference sequence by the steps of: performing a first mapping operation aligning the non-overlapping pairwise sequences to the at least one reference sequence with a selected mismatch constraint identifying non-overlapping pairwise sequences for which one of the non-overlapping pairwise sequences align to the at least one reference sequence while satisfying the selected mismatch constraint; performing a second mapping operation designating a window region of the reference sequence to align the non aligned pairwise sequence with a selected mismatch constraint; identifying non-overlapping pairwise sequences that are successfully mapped following performing the first and second mapping operations; and, outputting the results of the mapping operations. ### Claim 15 (depends on 14) The computer-readable medium of claim 14, 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 pairwise sequences and an observed intervening sequence length between the non-overlapping pairwise sequences. ### Claim 16 (depends on 15) The computer-readable medium of claim 15, wherein the indel comprises an insertion occurring between the non-overlapping pairwise sequences which accounts for the difference between the expected intervening sequence length and the observed intervening sequence length. ### Claim 17 (depends on 15) The computer-readable medium of claim 15, wherein the indel comprises a deletion occurring between the non-overlapping pairwise sequences which accounts for the difference between the expected intervening sequence length and the observed intervening sequence length. ### Claim 18 (depends on 14) The computer-readable medium of claim 14, wherein the non-overlapping sequence information comprises paired read sequence information separated by the intervening sequence whose distance is approximately known. ### Claim 19 (depends on 18) The computer-readable medium of claim 18, wherein each of the paired read sequences has a length of between approximately 10 and 75 bases. ### Claim 20 (depends on 19) The computer-readable medium of claim 19, wherein the intervening sequence has a length of between approximately 2 kilobases and 15 kilobases.