Hydroxymethylation analysis of cell-free nucleic acid samples for assigning tissue of origin, and related methods of use

A hydroxymethylation, reference hydroxymethylation technology, applied in the application of epigenetic analysis, biological field, can solve complex problems and other problems

Pending Publication Date: 2021-03-19
蓝星基因组股份有限公司
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  • Abstract
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Problems solved by technology

However, cell-free DNA analysis also presents unique challenges, especially since cell-free DNA samples are very small and typically contain only a few nanograms of DNA per milliliter of plasma
The problem is compounded when cell-free DNA is used in conjunction with epigenetic analysis, where relatively rare DNA modifications such as 5-methylcytosine and the even rarer 5-hydroxymethylcytosine need to be detected

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  • Hydroxymethylation analysis of cell-free nucleic acid samples for assigning tissue of origin, and related methods of use
  • Hydroxymethylation analysis of cell-free nucleic acid samples for assigning tissue of origin, and related methods of use
  • Hydroxymethylation analysis of cell-free nucleic acid samples for assigning tissue of origin, and related methods of use

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Embodiment Construction

[0070] The present invention provides a method of probabilistically assigning a tissue of origin to nucleic acids in a cell-free fluid sample, such as a cell-free DNA sample, obtained from a human subject. Related methods and systems are also provided, including diagnostic, prognostic, patient monitoring, and other methods. Larger reference sets of hydroxymethylation profiles, i.e., hydroxymethylome data containing hydroxymethylation data for multiple loci on each of multiple tissue-specific genes for multiple tissue types Similarity of detected nucleic acid hydroxymethylation profiles was assessed between sets.

[0071] 1. Terminology:

[0072] Unless otherwise defined, all technical and scientific terms used herein have the meaning commonly understood by one of ordinary skill in the art to which this invention belongs. Certain terms of particular importance to the description of the present invention are defined below. Other related terms are defined in International Pate...

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Abstract

A method is provided for probabilistically assigning a tissue of origin to a nucleic acid in a sample, e.g., DNA in a cell-free fluid sample obtained from a human subject. A hydroxymethylation profileis generated for the sample DNA and then compared across a reference data set of hydroxymethylation profile vectors, where each hydroxymethylation profile vector identifies the hydroxymethylation profile at a specific reference locus, the tissue-specific gene associated with the reference locus, and the tissue with which the gene and reference locus are associated. A tissue of origin can be probabilistically assigned to the sample nucleic acid using the results of the comparison. Other methods of use are also provided.

Description

technical field [0001] The present invention relates generally to biotechnology, and more particularly to the application of epigenetic analysis of cell-free DNA. The invention can be used in the research fields of genomics, medicine, diagnostics and epigenetics. Background technique [0002] In many fields related to medicine, such as diagnostics, therapeutics, and patient monitoring, there is a continuing need for more precise methods of analyzing biological samples and extracting useful information from those analyses, the goals of accuracy and efficiency often being competing. Analytical methods should be amenable to high-speed processing and automation, produce the necessary results quickly and cost-effectively, and provide high sensitivity and specificity. In addition, the information provided by analytical methods should be used to its fullest potential. For example, in a method for analyzing a patient's DNA, it would be desirable if the method could quickly provide...

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/6883C12Q1/6886
CPCC12Q1/6883C12Q1/6886C12Q2600/112C12Q2600/118C12Q2600/154G16H50/30G16B20/20G16B40/10C12Q1/6809C12Q1/6827C12Q2537/164C12Q2600/166C12Q2600/172
Inventor C-J.顾F.科林P.A.阿伦斯多夫S.莱维
Owner 蓝星基因组股份有限公司
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