Systems, Methods, and Compositions for Viral-Associated Tumors
AssigneeFive3 Genomics, LLC
InventorsJohn Zachary Sanborn, Charles Joseph Vaske, Stephen Charles Benz, Shahrooz Rabizadeh, Nicole Hensley, Patrick Soon-Shiong
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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.
Claims14
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.
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.
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.
Dependencies are inferred from the claim text.