# US 2018/0322245 A1 · Systems, methods, and compositions for viral-associated tumors > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2018/0322245 A1 - Document ID: US20180322245A1 - Status: Published application - Kind: A1 - Application number: 16/032,421 - Filed: 2018-07-11 - Published: 2018-11-08 - Earliest claimed: 2013-09-26 - Assignees: Five3 Genomics, LLC; Nant Holdings IP, LLC - Applicants: Five3 Genomics, LLC; Nant Holdings IP, LLC - Inventors: John Zachary Sanborn; Charles Joseph Vaske; Stephen Charles Benz; Shahrooz Rabizadeh; Nicole Hensley; Patrick Soon-Shiong - Web page: https://patentgrep.com/patent/US20180322245A1 ## CPC - G16B 30/10: Sequence alignment; Homology search - G16B 30/00: ICT specially adapted for sequence analysis involving nucleotides or amino acids - G16B: BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY ## Abstract Contemplated systems and methods employ chimeric reference sequences that include a plurality of viral genome sequences to identify/quantify integration and co-amplification events. Most typically, the viral genome sequences are organized in the chimeric reference sequences as single chromosomes and the chimeric reference sequences are in BAM format. ## Claims ### Claim 1 A method of identifying at least one of presence and integration of a nucleic acid of a pathogen in a nucleic acid sequence of a mammalian tissue, comprising: informationally coupling an analysis engine to a sequence database storing a nucleic acid sequence from a mammalian tissue and a chimeric reference nucleic acid sequence; wherein the chimeric reference nucleic acid sequence comprises at least one nucleic acid sequence of at least one pathogen and optionally a mammalian nucleic acid sequence; and aligning the chimeric reference nucleic acid sequence and the nucleic acid sequence from the mammalian tissue, using incremental synchronized alignment, by the analysis engine, to identify at least one of presence and integration of the nucleic acid sequence of the pathogen in the nucleic acid sequence from the mammalian tissue. ### Claim 2 (depends on 1) The method of claim 1 wherein the chimeric reference nucleic acid sequence comprises the at least one nucleic acid sequence of at least one pathogen and the mammalian nucleic acid sequence. ### Claim 3 (depends on 2) The method of claim 2 wherein the mammalian nucleic acid sequence is a matched normal mammalian nucleic acid sequence. ### Claim 4 (depends on 1) The method of claim 1 wherein the nucleic acid sequence from the mammalian tissue comprises at least nucleic acid sequences of one chromosome of the mammalian tissue. ### Claim 5 (depends on 1) The method of claim 1 wherein the nucleic acid sequence from the mammalian tissue comprises at least 50% of an exome of the mammalian tissue. ### Claim 6 (depends on 1) The method of claim 1 wherein the nucleic acid sequence from the mammalian tissue comprises at least 50% of an entire genome of the mammalian tissue. ### Claim 7 (depends on 1) The method of claim 1 wherein the chimeric reference nucleic acid sequence comprises nucleic acid sequences of a plurality of distinct pathogens. ### Claim 8 (depends on 1) The method of claim 1 wherein the pathogen is a virus. ### Claim 9 (depends on 8) The method of claim 8 wherein the virus is a virus selected from the group consisting of HTLV-1 (Human T-Cell Leukemia Virus), an HPV virus (Human Papillomavirus), HHV-8 (Human Herpes Virus 8), EBV (Epstein-Barr Virus), HBV (Hepatitis B Virus), HCV (Hepatitis C Virus), SV40 (Simian Vacuolating Virus 40), BKV (BK virus), JCV (JC virus), a HERV (human endogenous retrovirus), HMTV (human mammary tumor virus), KSHV (Kaposi's Sarcoma-Associated Herpesvirus), and TTV (Torque teno virus). ### Claim 10 (depends on 1) The method of claim 1 further comprising a step of identifying, by the analysis engine, an integration of at least some of the nucleic acid sequence of the at least one pathogen into the nucleic acid sequence from the mammalian tissue. ### Claim 11 (depends on 1) The method of claim 1 further comprising a step of identifying, by the analysis engine, a co-amplification of an allele of the nucleic acid sequence from the mammalian tissue and at least some of the nucleic acid sequence of the at least one pathogen. ### Claim 12 A method of generating a chimeric reference nucleic acid sequence, comprising: informationally coupling an editing engine to a sequence database storing a nucleic acid sequence from a mammalian tissue and a plurality of nucleic acid sequences from a plurality of respective distinct pathogens; merging, by the editing engine, the nucleic acid sequence from the mammalian tissue with the plurality of nucleic acid sequences from the pathogens into a single chimeric nucleic acid sequence file; wherein the nucleic acid sequence from the mammalian tissue is organized in the single chimeric nucleic acid sequence file following a chromosomal structure, and wherein each of the plurality of nucleic acid sequences from the pathogens is organized in the single chimeric nucleic acid sequence file as a single chromosome; and updating the sequence database with the single chimeric genomic file. ### Claim 13 (depends on 12) The method of claim 12 wherein the nucleic acid sequence from the mammalian tissue comprises at least 50% of an exome of the mammalian tissue. ### Claim 14 (depends on 12) The method of claim 12 wherein the nucleic acid sequence from the mammalian tissue comprises at least 50% of an entire genome of the mammalian tissue. ### Claim 16 (depends on 12) The method of claim 12 wherein the distinct pathogens are distinct viruses. ### Claim 17 (depends on 12) The method of claim 12 wherein the step of merging comprises appending to the nucleic acid sequence from the mammalian tissue the plurality of nucleic acid sequences from the pathogens. ### Claim 18 (depends on 12) The method of claim 12 wherein at least one of the nucleic acid sequence from the mammalian tissue, the plurality of nucleic acid sequences of the pathogens, and the single chimeric nucleic acid sequence file is in BAM, SAM, FASTA, or FASTA index format. ### Claim 19 (depends on 12) The method of claim 12 wherein the nucleic acid sequence from the mammalian tissue, the plurality of nucleic acid sequences from the pathogens, and the single chimeric nucleic acid sequence file are in BAM format. ### Claim 20 (depends on 12) The method of claim 12 wherein the nucleic acid sequence from the mammalian tissue is a matched normal sequence for the mammal.