Methods for using mosaicism in nucleic acids sampled distal to their origin
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Publication Number
US-11753686-B2
Publication Date
2023-09-12
Expiration Date
Abstract
Disclosed herein are methods for improving detection and monitoring of human diseases. The methods can be used to provide spatial and/or developmental localization of the source of each differential mutation within the body. The methods can also be used to generate a mutation map of a subject. And the mutation map can be used to monitoring state(s) of health of one or more tissues of a subject.
Core Innovation
The invention provides a method for identifying mosaic variants specific to a subject from a non-fetal source in a blood sample. Nucleic acid molecules are obtained from a plasma fraction comprising cell-free nucleic acid molecules and from a buffy coat fraction of the blood sample, and the nucleic acid molecules are assayed to generate sequence information derived from the plasma fraction and the buffy coat fraction.
The method identifies mosaic variants specific to the subject in the sequences derived from the plasma fraction by subtracting out a blood-specific signal derived from the sequences derived from the buffy coat fraction. The sequences derived from the buffy coat fraction are treated as normal for the purpose of isolating subject-specific mosaic variants in the plasma-derived sequences.
In the described approach, whole genome sequencing is used to generate sequence information from the plasma fraction and the buffy coat fraction. The subtraction of the blood-specific signal supports identifying mosaic variants that are not attributable to the normal buffy coat source, and a report is provided based on the identification of the mosaic variants specific to the subject.
Claims Coverage
The partial content includes one independent claim. The independent claim covers a plasma-versus-buffy-coat workflow for whole genome sequencing and blood-specific signal subtraction to identify subject-specific mosaic variants, followed by reporting.
Plasma and buffy coat nucle-acid sampling from non-fetal blood
Obtaining nucleic acid molecules from a plasma fraction comprising cell-free nucleic acid molecules and from a buffy coat fraction of a non-fetal blood sample from a subject.
Whole genome sequencing of plasma and buffy coat fractions
Assaying nucleic acid molecules from the plasma fraction and the buffy coat fraction to generate sequence information comprising sequences derived from the plasma fraction and sequences derived from the buffy coat fraction, wherein the assaying comprises whole genome sequencing.
Blood-specific signal subtraction to identify subject-specific mosaic variants
Identifying mosaic variants specific to the subject in sequences derived from the plasma fraction by subtracting out a blood-specific signal of sequences derived from the buffy coat fraction, wherein sequences derived from the buffy coat fraction are a normal.
Reporting based on identified mosaic variants
Providing a report based on an identification of the mosaic variants specific to the subject.
Overall, the claim scope centers on generating whole-genome sequence information from both plasma and buffy coat fractions, treating the buffy coat-derived sequences as normal, and identifying subject-specific mosaic variants in plasma by subtracting a blood-specific signal, with a report generated from the identified variants.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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