Systems, Methods, and Compositions for Viral-Associated Tumors

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.

What is claimed is: 
     
         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.   
     
     
         2 . 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. 
     
     
         3 . 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. 
     
     
         4 . The method of  claim 1 , wherein the distinct pathogens are distinct viruses. 
     
     
         5 . 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. 
     
     
         6 . 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. 
     
     
         7 . 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. 
     
     
         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.   
     
     
         9 . The method of  claim 8 , wherein the tumor is a bladder tumor. 
     
     
         10 . 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. 
     
     
         11 . 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. 
     
     
         12 . The method of  claim 8 , wherein the chimeric reference nucleic acid sequence comprises a nucleic acid sequence of an HPV virus of type 16. 
     
     
         13 . The method of  claim 8 , further comprising a step of determining a solution for a genomic arrangement comprising the co-amplified sequences. 
     
     
         14 . The method of  claim 8 , wherein the genomic arrangement is a circular solution or a tandem duplication.