Identification of dna fragments and structural variations
AssigneeComplete Genomics, Inc.
InventorsBahram Ghaffarzadeh Kermani, Radoje Drmanac, Oleg Alferov
Life of this patent
Estimating the term…
Abstract
Various short reads can be grouped and identified as coming from a same long DNA fragment (e.g., by using wells with a relatively low-concentration of DNA). A histogram of the genomic coverage of a group of short reads can provide the edges of the corresponding long fragment (pulse). The knowledge of these pulses can provide an ability to determine the haploid genome and to identify structural variations.
Claims37
A method of detecting a structural variation in a genome of a sample from an organism, the method comprising:
- receiving sequence data from a sequencing of a plurality of nucleic acid molecules of the sample, the sequence data including sequences of at least one portion of each nucleic acid molecule;
- for each nucleic acid molecule:
- aligning at least one sequence of the nucleic acid molecule to a reference genome;
- associating each aligned sequence with at least one other aligned sequence based on a presumption that the two sequences are potentially derived from a same fragment of DNA;
- calculating, with a computer system, each of a plurality of histograms for a first chromosomal region by:
- identifying a respective group of sequences as potentially being derived from a same fragment of DNA, the fragment including at least a portion of the first chromosomal region;
- for each genomic position of a plurality of genomic positions within the first chromosomal region:
- aggregating a number of instances that an aligned sequence of the respective group includes the genomic position;
- comparing the histograms to identify a common increase or decrease in the histograms within a same window of the first chromosomal region;
- identifying the common increase or decrease as a location of a structural variation in the first chromosomal region of the genome of the organism.
A computer product comprising a computer readable medium storing a plurality of instructions for controlling a computer system to perform an operation of detecting a structural variation in a genome of a sample from an organism, the instructions comprising:
- receiving sequence data from a sequencing of a plurality of nucleic acid molecules of the sample, the sequence data including sequences of at least one portion of each nucleic acid molecule;
- for each nucleic acid molecule:
- aligning at least one sequence of the nucleic acid molecule to a reference genome;
- associating each aligned sequence with at least one other aligned sequence based on a presumption that the two sequences are potentially derived from a same fragment of DNA;
- calculating each of a plurality of histograms for a first chromosomal region by:
- identifying a respective group of sequences as potentially being derived from a same fragment of DNA, the fragment including at least a portion of the first chromosomal region;
- for each genomic position of a plurality of genomic positions within the first chromosomal region:
- aggregating a number of instances that an aligned sequence of the respective group includes the genomic position;
- comparing the histograms to identify a common increase or decrease in the histograms within a same window of the first chromosomal region;
- identifying the common increase or decrease as a location of a structural variation in the first chromosomal region of the genome of the organism
A method of identifying DNA fragments from sequencing data of a sample of an organism, the method comprising:
- receiving sequence data from a sequencing of a plurality of nucleic acid molecules of a sample, the sequence data including sequences of at least one portion of each nucleic acid molecule;
- for each nucleic acid molecule:
- aligning at least one sequence of the nucleic acid molecule to a reference genome;
- associating each aligned sequence with at least one other aligned sequence based on a presumption that the two sequences are derived from a same fragment of DNA;
- calculating, with a computer system, a histogram for a first chromosomal region by:
- identifying a first group of aligned sequences as potentially being derived from a same fragment of DNA that includes at least a portion of the first chromosomal region;
- for each genomic position of a plurality of genomic positions within the first chromosomal region:
- aggregating a number of instances that an aligned sequence of the first group includes the genomic position;
- determining a genomic location of a pulse in the histogram, the genomic location of the pulse including a beginning of the pulse and an end of the pulse;
- and
- identifying the sample as having a first fragment of DNA that includes a sequence corresponding to the reference genome at the genomic location of the pulse.
Dependencies are inferred from the claim text.