Diagnosing cancer using genomic sequencing
First Claim
1. A method of analyzing a biological sample of a human for deletions or amplifications in one or more chromosomal regions associated with cancer, the biological sample including cell-free nucleic acid molecules originating from non-malignant cells and potentially from tumor cells associated with cancer, the method comprising:
- performing a random sequencing of nucleic acid molecules from biological sample by;
attaching adaptors to at least one end of the nucleic acid molecules; and
sequencing, using the adaptors, the nucleic acid molecules to obtain sequences, including at least 120,000 sequences;
receiving, at a computer system, the sequences obtained from the random sequencing of nucleic acid molecules contained in the biological sample;
aligning, by the computer system, at least a portion of the sequences to a human genome;
determining, by the computer system, a first amount of sequences identified as aligning to a first chromosomal region that is part of a first chromosome, wherein a deletion or an amplification in the first chromosomal region is associated with cancer;
determining, by the computer system, a second amount of sequences identified as aligning to one or more second chromosomal regions;
determining a first parameter from the first amount and the second amount, wherein the first parameter represents a relative amount between the first and second amounts; and
comparing the first parameter to one or more cutoff values to determine a classification of whether the first chromosomal region exhibits a deletion or an amplification associated with cancer in the human.
1 Assignment
0 Petitions
Accused Products
Abstract
Methods, systems, and apparatus determine whether a first chromosomal region exhibits a deletion or an amplification associated with cancer in a sample from a subject (e.g., where the sample includes a mixture of cell-free DNA from tumor cells and non-malignant cells. Nucleic acid molecules of the biological sample are sequenced. Respective amounts of a clinically-relevant chromosomal region and of background chromosomal region(s) are determined from results of the sequencing. A parameter derived from these amounts (e.g. a ratio) is compared to one or more cutoff values, thereby determining a classification of whether first chromosomal region exhibits a deletion or an amplification associated with cancer.
176 Citations
29 Claims
-
1. A method of analyzing a biological sample of a human for deletions or amplifications in one or more chromosomal regions associated with cancer, the biological sample including cell-free nucleic acid molecules originating from non-malignant cells and potentially from tumor cells associated with cancer, the method comprising:
-
performing a random sequencing of nucleic acid molecules from biological sample by; attaching adaptors to at least one end of the nucleic acid molecules; and sequencing, using the adaptors, the nucleic acid molecules to obtain sequences, including at least 120,000 sequences; receiving, at a computer system, the sequences obtained from the random sequencing of nucleic acid molecules contained in the biological sample; aligning, by the computer system, at least a portion of the sequences to a human genome; determining, by the computer system, a first amount of sequences identified as aligning to a first chromosomal region that is part of a first chromosome, wherein a deletion or an amplification in the first chromosomal region is associated with cancer; determining, by the computer system, a second amount of sequences identified as aligning to one or more second chromosomal regions; determining a first parameter from the first amount and the second amount, wherein the first parameter represents a relative amount between the first and second amounts; and comparing the first parameter to one or more cutoff values to determine a classification of whether the first chromosomal region exhibits a deletion or an amplification associated with cancer in the human. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29)
-
Specification