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US 12,517,133 B2Granted
Macromolecule analysis employing nucleic acid encoding
OwnerMark S. Chee, Kevin L. Gunderson +1inventors
InventorsMark S. Chee, Kevin L. Gunderson, Michael Phillip Weiner
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Abstract
A method for analyzing macromolecules, including peptides, polypeptides, and proteins, employing nucleic acid encoding is disclosed.
Claims17
A method of analyzing a polypeptide of a spatial sample, the method comprising:
- (a) attaching the polypeptide to a nucleic acid recording tag within the spatial sample;
- (b) contacting the spatial sample with an array of spatial barcode molecules, wherein each of the spatial barcode molecules comprises a nucleic acid sequence that reflects a spatial position of the spatial barcode molecule within the array and further comprises a nucleic acid sequence configured to hybridize with a portion of the nucleic acid recording tag;
- (c) cleaving spatial barcode molecules from the array and allowing them to diffuse into the spatial sample and hybridize to the nucleic acid recording tag attached to the polypeptide within the spatial sample;
- (d) generating an extended nucleic acid recording tag attached to the polypeptide by transferring information of a hybridized spatial barcode molecule to the nucleic acid recording tag attached to the polypeptide;
- and
- (e) analyzing the extended nucleic acid recording tag, wherein the analyzing comprises a nucleic acid sequencing method, to obtain information about location of the polypeptide within the spatial sample.
3 more elements
A method of analyzing a polypeptide of a spatial sample, the method comprising:
- (a) attaching the polypeptide to a nucleic acid recording tag within the spatial sample;
- (b) contacting the spatial sample with an array of spatial barcode molecules, wherein each of the spatial barcode molecules comprises a nucleic acid sequence that reflects a spatial position of the spatial barcode molecule within the array and further comprises a nucleic acid sequence configured to hybridize with a portion of the nucleic acid recording tag;
- (c) fragmenting the polypeptide attached to the nucleic acid recording tag, thereby generating a peptide attached to the nucleic acid recording tag, and allowing the peptide and the attached nucleic acid recording tag to diffuse to the array and hybridize to one of the spatial barcode molecules within the array;
- (d) generating an extended nucleic acid recording tag attached to the peptide by transferring information of the hybridized spatial barcode molecule to the nucleic acid recording tag attached to the peptide;
- and
- (e) analyzing the extended nucleic acid recording tag, wherein the analyzing comprises a nucleic acid sequencing method, to obtain information about location of the polypeptide within the spatial sample.
3 more elements
Dependencies are inferred from the claim text.