Methods of monitoring conditions by sequence analysis
AssigneeAdaptive Biotechnologies Corporation
InventorsMalek Faham, Thomas Willis
Life of this patent
Estimating the term…
Abstract
There is a need for improved methods for determining the diagnosis and prognosis of patients with conditions, including autoimmune disease and cancer. Provided herein are methods for using DNA sequencing to identify personalized biomarkers in patients with autoimmune disease and other conditions. Identified biomarkers can be used to determine the disease state for a subject with an autoimmune disease or other condition.
Claims19
A method of assessing transplant rejection in an organ transplant recipient, comprising:
- (a) amplifying molecules of nucleic acids comprising sequences of complementarity determining region 3 (CDR3) from T-cell receptor or B-cell receptor genes in a sample of lymphocytes obtained from the transplant recipient pre-transplant;
- (b) isolating and sequencing the amplified molecules in the lymphocyte sample to provide a repertoire of CDR3 sequences comprising at least 1000 sequence reads of at least 30 bp;
- (c) amplifying molecules of nucleic acids comprising sequences of CDR3 from T-cell receptor or B-cell receptor genes in a biopsy sample of the transplant graft obtained from the transplant recipient post-transplant;
- (d) isolating and sequencing the amplified molecules in the biopsy sample to provide a repertoire of CDR3 sequences comprising at least 1000 sequence reads of at least 30 bp, and identifying correlating clonotypes more prevalent in the biopsy sample compared to the lymphocyte sample;
- (e) amplifying molecules of nucleic acids comprising sequences of CDR3 from T-cell receptor or B-cell receptor genes in a blood sample obtained from the transplant recipient post-transplant;
- (f) isolating and sequencing the amplified molecules in the blood sample to provide a repertoire of CDR3 sequences comprising at least 1000 sequence reads of at least 30 bp;
- and,
- (g) assessing whether rejection of the transplant is occurring by confirming the presence and/or level of correlating clonotypes identified in step (d) among the sequences generated in step (f).
A method of quantitatively measuring clonotypes correlating to transplant rejection in an organ transplant recipient, comprising:
- (a) amplifying molecules of nucleic acids comprising sequences of complementarity determining region 3 (CDR3) from T-cell receptor or B-cell receptor genes in a sample of lymphocytes obtained from the transplant recipient pre-transplant;
- (b) isolating and sequencing the amplified molecules in the lymphocyte sample to provide a repertoire of CDR3 sequences comprising at least 1000 sequence reads of at least 30 bp;
- (c) amplifying molecules of nucleic acids comprising sequences of CDR3 from T-cell receptor or B-cell receptor genes in a biopsy sample of the transplant graft obtained post-transplant;
- (d) isolating and sequencing the amplified molecules in the biopsy sample to provide a repertoire of CDR3 sequences comprising at least 1000 sequence reads of at least 30 bp, and identifying clonotypes more prevalent in the biopsy sample compared to the lymphocyte sample as clonotypes correlating to transplant rejection;
- and
- (e) producing a quantitative profile of clonotypes identified in step (d) that correlate to transplant rejection in the organ transplant recipient.
Dependencies are inferred from the claim text.