Compositions and methods of using rna fragments

Abstract

The present invention includes a method for analyzing RNA fragments. In one aspect, the present invention includes a method of identifying a subject in need of therapeutic intervention to treat a disease or condition, disease recurrence, or disease progression comprises characterizing the identity of rRNA fragments. The invention also includes diagnosing, identifying or monitoring a disease or condition, and a method for identifying rRNA fragments. The invention also includes diagnosing, identifying or monitoring a glaucoma in a subject in need thereof by characterizing the identity of rRNA or tRNA fragments.

What is claimed is: 
     
         1 . A method of identifying a subject in need of therapeutic intervention to treat a disease or condition, disease recurrence, or disease progression comprising:
 isolating fragments of rRNAs from a sample obtained from the subject; and   characterizing the rRNA fragments and their relative abundance in the sample to identify a signature, wherein when the signature is indicative of a diagnosis of the disease, a treatment of the subject is recommended.   
     
     
         2 . The method of  claim 1 , wherein the sample is isolated from a cell, tissue or body fluid obtained from the subject. 
     
     
         3 . The method of  claim 2 , wherein the body fluid is selected from the group consisting of amniotic fluid, aqueous humour and vitreous humour, bile, blood serum, breast milk, cerebrospinal fluid, cerumen, chyle, chyme, endolymph and perilymph, exudates, feces, female ejaculate, gastric acid, gastric juice, lymph, mucus, pericardial fluid, peritoneal fluid, pleural fluid, pus, rheum, saliva, sebum, serous fluid, semen, smegma, sputum, synovial fluid, sweat, tears, urine, vaginal secretion, and vomit. 
     
     
         4 . The method of  claim 1 , wherein isolating the rRNA fragments comprises isolating rRNA fragments with a length in the range of about 15 nucleotides to about 50 nucleotides. 
     
     
         5 . The method of  claim 1 , wherein the signature comprises at least one sequence selected from the group consisting of SEQ ID NOs: 1-66149 and 70852-71358. 
     
     
         6 . The method of  claim 1 , wherein characterizing the rRNA fragments comprises at least one assessment selected from the group consisting of sequencing the rRNA fragments, measuring overall abundance of one of the rRNA fragments mapped to the genome, measuring a relative abundance of the one rRNA fragment to a reference, assessing a length of the one rRNA fragment, identifying starting and ending points of the one rRNA fragment, identifying genomic origin of the one rRNA fragment, and identifying a terminal modification of the one rRNA fragment. 
     
     
         7 . The method of  claim 1 , wherein the signature distinguishes a normal state as compared to disease state or condition. 
     
     
         8 . The method of  claim 1 , wherein the disease or condition, disease recurrence, or disease progression is selected from the group consisting of a cancer, a brain disease, a glaucoma and a genetically predisposed disease or condition. 
     
     
         9 . The method of  claim 8 , wherein the cancer is selected from the group consisting of adrenocortical carcinoma, bladder urothelial carcinoma, breast invasive carcinoma, triple negative breast cancer, cervical squamous cell carcinoma and endocervical adenocarcinoma, cholangiocarcinoma, coad-colon adenocarcinoma, lymphoid neoplasm diffuse large b-cell lymphoma, esophageal carcinoma, head and neck squamous cell carcinoma, kidney chromophobe, kidney renal clear cell carcinoma, kidney renal papillary cell carcinoma, acute myeloid leukemia, brain lower grade glioma, liver hepatocellular carcinoma, lung adenocarcinoma, lung squamous cell carcinoma, mesothelioma, ovarian serous cystadenocarcinoma, pancreatic adenocarcinoma, pheochromocytoma and paraganglioma, prostate adenocarcinoma, rectum adenocarcinoma, sarcoma, skin cutaneous melanoma, stomach adenocarcinoma, testicular germ cell tumors, thyroid carcinoma, thymoma, uterine corpus endometrial carcinoma, uterine carcinosarcoma, and uveal melanoma, leukemia, chronic lymphocytic leukemia, and triple negative breast cancer. 
     
     
         10 . The method of  claim 8 , wherein the glaucoma is a primary open angle glaucoma (POAG). 
     
     
         11 . The method of  claim 10 , wherein the signature of the POAG comprises at least one sequence selected from the group consisting of SEQ ID NOs: 65474-66149 and 70852-71358. 
     
     
         12 . The method of  claim 8 , wherein the brain disease is Alzheimer's disease. 
     
     
         13 . A method of diagnosing, identifying or monitoring a cancer in a subject in need thereof, the method comprising:
 isolating rRNA fragments from a cell obtained from the subject;   quantifying the RNA fragments using a panel of oligonucleotides engineered to detect rRNA fragments or other method;   analyzing levels of the rRNA fragments present in the cell; wherein a differential in the level of measured rRNA fragments as compared to a reference is indicative of a diagnosis or identification of a cancer in the subject; and   providing a treatment regimen to the subject dependent on the differential in the level of measured rRNA fragments as compared to the reference.   
     
     
         14 . A method of determining the race and sex of a subject in need thereof, the method comprising:
 isolating fragments of rRNAs from a sample obtained from the subject;   characterizing the identity of the rRNA fragments and their relative abundance in the sample to identify a signature, wherein the signature is indicative of the race and sex of the subject; and   recommending or providing a personalized treatment regimen or a disease prognosis to the subject based upon the subject's race and/or sex.   
     
     
         15 . The method of  claim 14 , wherein the signature comprises at least one sequence selected from the group consisting of SEQ ID NOs: 1-28515. 
     
     
         16 . A method for identifying rRNA fragments comprising:
 defining rRNA loci;   sequencing a population of RNA fragments; and   mapping the sequenced RNA fragments to at least one rRNA genomic loci.   
     
     
         17 . The method of  claim 16 , wherein the rRNA genomic loci comprise mitochondrial rRNA sequences from the mitochondrial genome, nuclear rRNA sequences from the nuclear genome, and mitochondria rRNA sequences from the nuclear genome. 
     
     
         18 . The method of  claim 16 , wherein characterizing the mapped rRNA fragments comprises at least one assessment selected from the group consisting of identifying one or more of the mapped RNA fragments in a population, measuring an overall abundance of one or more of the mapped RNA fragments, measuring a relative abundance of one or more of the mapped RNA fragments to a reference, assessing a length of one or more of the mapped RNA fragments, identifying starting and ending points of one or more of the mapped RNA fragments, and identifying genomic origin of one or more of the mapped RNA fragments. 
     
     
         19 . A kit for high-throughput analysis of rRNAs fragments in a sample from a subject in need thereof, the kit comprising a collection specially-designed qPCR assays for quantitating rRNA fragments, or panel of engineered oligonucleotides capable of hybridizing rRNA fragments, or other quantification method. 
     
     
         20 . A method of identifying a subject at risk for developing a glaucoma disorder or in need of therapeutic intervention to treat a glaucoma disorder, the method comprising:
 isolating fragments of tRNAs from a sample obtained from the subject; and   characterizing the tRNA fragments and their relative abundance in the sample to identify a signature, wherein when the signature is indicative of a prognosis for developing a glaucoma or a diagnosis for a glaucoma, a treatment of the subject is recommended.   
     
     
         21 . The method of  claim 20 , wherein the sample is isolated from a cell, tissue or body fluid obtained from the subject. 
     
     
         22 . The method of  claim 21 , wherein the body fluid is selected from the group consisting of amniotic fluid, aqueous humour and vitreous humour, bile, blood serum, breast milk, cerebrospinal fluid, cerumen, chyle, chyme, endolymph and perilymph, exudates, feces, female ejaculate, gastric acid, gastric juice, lymph, mucus, pericardial fluid, peritoneal fluid, pleural fluid, pus, rheum, saliva, sebum, serous fluid, semen, smegma, sputum, synovial fluid, sweat, tears, urine, vaginal secretion, and vomit. 
     
     
         23 . The method of  claim 20 , wherein isolating the tRNA fragments comprises isolating tRNA fragments with a length in the range of about 15 nucleotides to about 50 nucleotides. 
     
     
         24 . The method of  claim 20 , wherein the signature comprises at least one sequence selected from the group consisting of SEQ ID NOs: 66150-70851 and 71359-71880. 
     
     
         25 . The method of  claim 20 , wherein characterizing the tRNA fragments comprises at least one assessment selected from the group consisting of sequencing the tRNA fragments, measuring overall abundance of one of the tRNA fragments mapped to the genome, measuring a relative abundance of the one tRNA fragment to a reference, assessing a length of the one tRNA fragment, identifying starting and ending points of the one tRNA fragment, identifying genomic origin of the one tRNA fragment, and identifying a terminal modification of the one tRNA fragment. 
     
     
         26 . The method of  claim 20 , wherein the signature distinguishes a normal state as compared to a disease state. 
     
     
         27 . A method of diagnosing, identifying or monitoring a glaucoma in a subject in need thereof, the method comprising:
 isolating tRNA fragments from a cell obtained from the subject;   quantitating tRNA fragments using a collection of specially-designed qPCR assays or a panel of engineered oligonucleotides capable of hybridizing tRNA fragments, or other quantification method;   analyzing levels of the tRNA fragments present in the cell; wherein a differential in the level of measured tRNA fragments as compared to a reference is indicative of a diagnosis or identification of a cancer in the subject; and   providing a treatment regimen to the subject dependent on the differential in the level of measured tRNA fragments as compared to the reference.   
     
     
         28 . The method of  claim 20 , wherein the glaucoma is a primary open angle glaucoma (POAG). 
     
     
         29 . The method of  claim 1 , wherein the subject is a human.