Methods and compositions for tracking nucleic acid fragment origin for nucleic acid sequencing

Abstract

The present disclosure provides methods and compositions for tracking nucleic acid fragment origin by target-specific barcode tagging when original nucleic acid targets break into small fragments. Nucleic acid targets are captured in vitro on a solid support with clonally localized nucleic acid barcode templates. Many nucleic acid targets can be processed simultaneously in a massively parallel fashion without partition. These nucleic acid target tracking methods can be used for a variety of applications in both whole genome sequencing and targeted sequencing in order to accurately identify genomic variants, haplotype phasing and assembly, for example.

What is claimed: 
     
         1 . A method of detecting a sequencing error in a barcode among a population of unique barcodes wherein each unique barcode is designed to comprise a plurality of barcode reads comprising
 a. identifying a first unique barcode among the population of unique barcodes, wherein the first unique barcode comprises only one barcode read;   b. comparing the sequence of the first unique barcode with the population of unique barcodes; and   c. identifying a second unique barcode among the population of unique barcodes, wherein the second unique barcode differs from the first unique barcode with less than four degenerate base mismatches and wherein the second unique barcode comprises a plurality of barcode reads.   
     
     
         2 . The method of  claim 1 , wherein the second unique barcode differs from the first unique barcode in less than three degenerate base mismatches. 
     
     
         3 . The method of  claim 1 , wherein the second unique barcode differs from the first unique barcode in less than two degenerate base mismatches. 
     
     
         4 . The method of  claim 1 , further comprising correcting the mismatches in the first unique barcode. 
     
     
         5 . The method of  claim 1 , wherein each barcode read is associated with a barcode. 
     
     
         6 . The method of  claim 1 , wherein the barcode read is in the form of information other than sequence, so long as the information is associated with the barcode. 
     
     
         7 . The method of  claim 6 , wherein the information is selected from the list consisting of color, index, ID, cluster, location, container, compartment information, and a combination thereof.