# US 2022/0277809 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 2022/0277809 A1 - Document ID: US20220277809A1 - Status: Published application - Kind: A1 - Application number: 17/739,792 - Filed: 2022-05-09 - Published: 2022-09-01 - Earliest claimed: 2018-07-11 - Assignees: Five3 Genomics, LLC - Applicants: Five3 Genomics, LLC - Inventors: John Zachary Sanborn; Charles Joseph Vaske; Stephen Charles Benz; Shahrooz Rabizadeh; Nicole Hensley; Patrick Soon-Shiong - Web page: https://patentgrep.com/patent/US20220277809A1 ## 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 generating a chimeric reference nucleic acid sequence for identification of co-amplification of an oncogene sequence of a mammalian tissue and at least some of the nucleic acid sequence of at least one pathogen, comprising: receiving, from a sequence database, a nucleic acid sequence from a mammalian tissue and a plurality of nucleic acid sequences from a plurality of respective distinct pathogens; merging the nucleic acid sequence from the mammalian tissue with the plurality of nucleic acid sequences from the pathogens to generate a single chimeric reference 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; wherein the pathogen 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); and updating the sequence database with the single chimeric genomic file. ### Claim 2 (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 3 (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 4 (depends on 1) The method of claim 1, wherein the distinct pathogens are distinct viruses. ### Claim 5 (depends on 11) The method of claim 11 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 6 (depends on 1) The method of claim 1, 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 7 (depends on 1) The method of claim 1, 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 8 A method of treating a tumor in a patient in need thereof, the method comprising receiving a chimeric reference whole genome nucleic acid sequence comprising a whole genome nucleic acid portion from a normal tissue sample of the patient and at least one viral nucleic acid sequence of a HPV (Human Papillomavirus) virus; obtaining a tumor whole genome nucleic acid sequence from the patient; aligning the chimeric reference nucleic acid sequence with tumor whole genome nucleic acid sequence of a patient tumor tissue to identify an integration of the HPV virus in an oncogene of the patient tumor tissue, and identifying co-amplification of the oncogene and the at least some of the HPV viral nucleic acid sequence; and treating, upon co-amplification reaching a threshold value, the tumor in the patient by administering a drug targeting the oncogene. ### Claim 9 (depends on 8) The method of claim 8, wherein the tumor is a bladder tumor. ### Claim 10 (depends on 8) The method of claim 8, wherein the chimeric reference nucleic acid sequence comprises at least two nucleic acid sequences of an HPV virus of type 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 69, 73, or 82. ### Claim 11 (depends on 10) The method of claim 10, wherein the at least two nucleic acid sequences of the HPV virus cover the entire genome of the HPV virus. ### Claim 12 (depends on 8) The method of claim 8, wherein the chimeric reference nucleic acid sequence comprises a nucleic acid sequence of an HPV virus of type 16. ### Claim 13 (depends on 8) The method of claim 8, further comprising a step of determining a solution for a genomic arrangement comprising the co-amplified sequences. ### Claim 14 (depends on 8) The method of claim 8, wherein the genomic arrangement is a circular solution or a tandem duplication.