Detection of human leukocyte antigen loss of heterozygosity
AssigneeTempus Labs, Inc.
InventorJason Perera
Life of this patent
Estimating the term…
Abstract
Processes are provided for detecting loss of heterozygosity of Human Leukocyte Antigen (HLA) in a subject using analysis of next generation sequencing (NGS) data. The processes include aligning NGS data and identifying unmapped and mapped reads, updating reference data, and feeding one or more sequence reads to an HLA typing process for identifying candidate HLA alleles and feeding HLA type data to a loss of heterozygosity (LOH) modeling process for determining a LOH status for each HLA allele. A report may be generated of the LOH statuses for each of HLA allele.
Claims30
A computer-implemented method of detecting loss of heterozygosity (LOH) of a human leukocyte antigen (HLA) gene in a subject, the method comprising:
- receiving next generation sequencing data generated from a biological sample of the subject;
- aligning the next generation sequencing data against a reference genome to determine a mapped reads dataset and an unmapped reads dataset;
- providing at least the unmapped reads dataset to an HLA typing process to identify at least one candidate HLA allele for the HLA gene;
- identifying a HLA sequence associated with each identified candidate HLA allele;
- creating a HLA reference genome using each identified HLA sequence;
- aligning the next generation sequencing data against the HLA reference genome and adjusting the HLA reference genome to account for a variant identified during the aligning;
- aligning the next generation sequencing data against the adjusted HLA reference genome to determine at least one read depth coverage measures, wherein the at least one read depth coverage measures is associated with a segment of the adjusted HLA reference genome associated with one of the identified candidate HLA alleles;
- providing the at least one read depth coverage measures to a LOH modeling process;
- determining, using the LOH modeling process, a LOH status for the HLA gene;
- and
- generating and storing a report of the LOH status for the HLA gene.
A computer-implemented method of creating a HLA reference genome specific to a subject, the method comprising:
- receiving normal next generation sequencing data generated from a buffy coat preparation of a blood sample of the subject;
- aligning the next generation sequencing data against a reference genome to determine a normal mapped reads dataset and a normal unmapped reads dataset;
- receiving tumor next generation sequencing data generated from a tumor specimen of the subject;
- providing at least a portion of the normal unmapped reads dataset to an HLA typing process to identify at least one candidate HLA allele for the HLA gene;
- identifying a HLA sequence associated with each identified candidate HLA allele;
- and
- creating a HLA reference genome using each identified HLA sequence.
A computer-implemented method of detecting loss of heterozygosity (LOH) of a human leukocyte antigen (HLA) gene in a subject, the method comprising:
- receiving normal next generation sequencing data generated from a buffy coat preparation of a blood sample of the subject;
- aligning the next generation sequencing data against a reference genome to determine a normal mapped reads dataset and a normal unmapped reads dataset;
- receiving tumor next generation sequencing data generated from a tumor specimen of the subject;
- providing at least a portion of the normal unmapped reads dataset to an HLA typing process to identify at least one candidate HLA allele for the HLA gene;
- identifying a HLA sequence associated with each identified candidate HLA allele;
- creating a HLA reference genome using each identified HLA sequence;
- aligning the normal next generation sequencing dataset against the HLA reference genome and adjusting the HLA reference genome to account for a variant identified during the aligning;
- aligning the normal next generation sequencing dataset against the adjusted HLA reference genome to determine at least one normal read depth coverage measures, wherein the at least one normal read depth coverage measures is associated with a segment of the adjusted HLA reference genome associated with one of the identified candidate HLA alleles;
- aligning the tumor next generation sequencing dataset against the adjusted HLA reference genome to determine at least one tumor read depth coverage measures, wherein the at least one tumor read depth coverage measures is associated with a segment of the adjusted HLA reference genome associated with one of the identified candidate HLA alleles;
- providing the at least one normal read depth coverage measures and the at least one tumor read depth coverage measures to a LOH modeling process;
- determining, using the LOH modeling process, a LOH status for the HLA gene;
- and
- generating and storing a report of the LOH status for the HLA gene.
Dependencies are inferred from the claim text.