A method for determining the tissue or cell of origin of dna
AssigneesYissum Research Development Company of the Hebrew University of Jerusalem, Hadasit Medical Research Services and Development Ltd.
InventorsYuval DOR, Ruth SHEMER, Benjamin GLASER, Tomer KAPLAN
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Abstract
Methods of detecting death of a cell type or tissue in a subject comprising determining the origin of cfDNA by ascertaining the methylation status of two or three methylation sites on a cfDNA molecule of no more than 167 nucleotides is provided. Methods of identifying regions of genomic DNA comprising no more than 167 nucleotides whose methylation signature distinguishes the origin of the region are also provided. Kits for use in performing the methods of the invention are also provided.
Claims21
A method of detecting cell type or tissue origin of DNA in a subject comprising determining whether cell-free DNA (cfDNA) comprised in a fluid sample of the subject is derived from the cell type or tissue, wherein said determining is effected by ascertaining the methylation status of two or three methylation sites on a continuous sequence of the cfDNA, said sequence comprising no more than 167 nucleotides, wherein a methylation status of each of said two or three methylation sites on said continuous sequence of the DNA characteristic of said cell type or tissue is indicative of death of the cell type or tissue.
A method of identifying a subregion of genomic DNA comprising no more than 167 nucleotides whose methylation signature in a cell type or tissue of interest distinguishes it from a second non-identical cell type or tissue, the method comprising:
- a. identifying in genomic DNA of said cell type or tissue of interest a plurality of methylation sites that are each differentially methylated with respect to said second non-identical cell type or tissue of interest;
- b. selecting from said plurality of sites at least one site, wherein said at least one site is located in a region comprising at least 6 CpGs within 167 nucleotides upstream and 167 nucleotides downstream of said at least one site;
- and
- c. identifying with said region of genomic DNA a subregion comprising no more than 167 nucleotides and 2 or 3 methylation sites wherein each of said 2 or 3 sites comprise the same methylation status and are differentially methylated with respect to said second non-identical cell type or tissue of interest;
- thereby identifying a subregion of genomic DNA comprising no more than 167 nucleotides.
A system for identifying a subregion of genomic DNA comprising no more than 167 nucleotides whose methylation signature in a cell type or tissue of interest distinguishes it from a second non-identical cell type or tissue, the system comprising a non-transitory memory device, wherein modules of instruction code are stored, and at least one processor associated with the memory device, and configured to execute the modules of instruction code, whereupon execution of said modules of instruction code, the at least one processor is configured to:
- identify in genomic DNA of said cell type or tissue of interest a plurality of methylation sites that are each differentially methylated with respect to said second non-identical cell type or tissue of interest;
- select from said plurality of sites at least one site, wherein said at least one site is located in a region comprising at least 6 CpGs within 150 nucleotides upstream and 150 nucleotides downstream of said at least one site;
- and
- identify with said region of genomic DNA a subregion comprising no more than 167 nucleotides and 2 or 3 methylation sites wherein each of said 2 or 3 sites comprise the same methylation status and are differentially methylated with respect to said second non-identical cell type or tissue of interest.
(canceled)
Dependencies are inferred from the claim text.