Determining cell type origin of circulating cell-free dna with molecular counting
AssigneeBellwether Bio, Inc.
InventorMatthew William SNYDER
Life of this patent
Estimating the term…
Abstract
Provided herein are compounds, methods, and compositions for use in determining the cellular origin of circulating cell-free DNA.
Claims15
A method of determining tissues and/or cell types giving rise to cell-free DNA (cfDNA) in a subject, the method comprising:
- a. isolating cfDNA from a biological sample from the subject, the isolated cfDNA comprising a plurality of cfDNA fragments;
- b. tagging a unique molecular identifier (UMI) to each isolated cfDNA fragment, the UMI comprising an oligomer of at least two nucleotides;
- c. determining pairs of sequences associated with at least a portion of the plurality of UMI-tagged cfDNA fragments;
- d. determining the subset of these pairs of sequences for which the sequence associated with the cfDNA fragment has more than one genomic location within a reference genome;
- and
- e. determining at least some of the tissues and/or cell types giving rise to the cfDNA fragments as a function of this subset of pairs of sequences.
The method of any preceding claim further comprising generating a report comprising a list of the determined tissues and/or cell types giving rise to the isolated cfDNA.
A method of identifying a disease or disorder in a subject, the method comprising:
- a. isolating cfDNA from a biological sample from the subject, the isolated cfDNA comprising a plurality of cfDNA fragments;
- b. tagging a unique molecular identifier (UMI) to each isolated cfDNA fragment, the UMI comprising an oligomer of at least two nucleotides;
- c. determining pairs of sequences associated with at least a portion of the plurality of UMI-tagged cfDNA fragments;
- d. determining the subset of these pairs of sequences for which the sequence associated with the cfDNA fragment has more than one genomic location within a reference genome;
- e. determining at least some of the tissues and/or cell types giving rise to the cfDNA fragments as a function of this subset of pairs of sequences;
- and
- f. identifying the disease or disorder as a function of the determined tissues and/or cell types giving rise to the cfDNA.
The method of any preceding claim wherein the reference genome is associated with a human.
The method of any preceding claim comprising generating a report comprising a statement identifying the disease or disorder.
The method of any preceding claim wherein the biological sample comprises, consists essentially of, or consists of whole blood, peripheral blood plasma, urine, or cerebral spinal fluid.
Dependencies are inferred from the claim text.