SEQUENCING ANALYSIS OF CIRCULATING DNA TO DETECT AND MONITOR AUTOIMMUNE DISEASES

摘要

Systems, methods, and apparatuses are provided for diagnosing auto-immune diseases such as systemic lupus erythematosus (SLE) based on the sizes, methylation levels, and/or genomic characteristics of circulating DNA molecules. Patients provide blood or other tissue samples containing cell-free nucleic molecules for analysis. Massively parallel and/or methylation-aware sequencing can be used to determine the sizes and methylation levels of individual DNA molecules and identify the number of molecules originating from different genomic regions. A level of SLE can be estimated based on: the amount of molecules having sizes below a threshold value; the methylation level(s) of the entire genome or portions of the genome; correlations between the sizes and methylation levels of DNA molecules; and/or comparing the representation of DNA molecules in each of a plurality of genomic regions with a reference value for that region, and determining an amount of genomic regions having increased or decreased measured genomic representation.

主权项

1. A method of analyzing a biological sample of an organism, the biological sample including nucleic acid molecules, wherein at least some of the nucleic acid molecules are cell-free, the method comprising:
analyzing a plurality of DNA molecules from the biological sample, wherein analyzing a DNA molecule comprises:
determining a size of the DNA molecule, andcomparing the size of the DNA molecule with a threshold value; determining, with a computer system, an amount of the DNA molecules having sizes below the threshold value; and estimating a first level of an auto-immune disease in the organism based upon the amount.