Systems and methods for using sequencing data for pathogen detection
Systems and methods are provided for training a classifier to discriminate between a first cancer condition associated with an oncogenic pathogenic infection a second cancer condition that is not associated with an oncogenic pathogenic infection. Systems and methods are provided for distinguishing cancers associated with oncogenic pathogenic infections that contribute to the cancer pathology and cancers that are not associated with oncogenic pathogenic infections. Systems and methods are provided for treating cancer based on whether the cancer is associated with an oncogenic pathogenic infection.
1. A method for discriminating between a first cancer condition and a second cancer condition in a subject with cervical cancer, wherein the first cancer condition is associated with human papilloma virus (HPV) infection and the second cancer condition is associated with an HPV-free status, the method comprising:
at a computer system comprising at least one processor and a memory storing at least one program for execution by the at least one processor
(A) obtaining a dataset for the subject, the dataset comprising a plurality of abundance values, wherein each respective abundance value in the plurality of abundance values quantifies a level of expression of a corresponding gene, in a discriminating gene set, in a cancerous tissue from the subject;
(B) inputting the dataset to a classifier trained to discriminate between at least the first cancer condition and the second cancer condition based on abundance values for the discriminating gene set in a cancerous tissue of a subject, thereby determining a cancer condition of the subject; and
(C) treating the subject for cancer by:
when the classifier result indicates that the subject has cervical cancer associated with an HPV infection, administering a first therapy tailored for treatment of cervical cancer associated with an HPV infection, and
when the classifier result indicates that the subject has cervical cancer not associated with an HPV infection, administering a second therapy tailored for treatment of cervical cancer not associated with an HPV infection.
2. The method of claim 1 , wherein the dataset further comprises a variant allele count for one or more variant alleles at one or more locus in the genome of the cancerous tissue from the subject.
3. The method of claim 1 , wherein the discriminating gene set comprises at least five genes selected from the group consisting of KRT86, CRISPLD1, DSG1, SESN3, ADAMTS20, IRX1, SMC1B, CDKN2A, EFNB3, CXCL14, ZFR2, RNF212, MKRN3, SYCP2, MYL1, MYO3A, RNASE10, GALNT13, C19orf26, MUC4, PCDHGB1, CCND1, LCE1F, and KCNS1.
4. The method of claim 3 , wherein the discriminating gene set comprises at least ten genes selected from the group consisting of KRT86, CRISPLD1, DSG1, SESN3, ADAMTS20, IRX1, SMC1B, CDKN2A, EFNB3, CXCL14, ZFR2, RNF212, MKRN3, SYCP2, MYL1, MYO3A, RNASE10, GALNT13, C19orf26, MUC4, PCDHGB1, CCND1, LCE1F, and KCNS1.
5. The method of claim 3 , wherein the discriminating gene set comprises at least twenty genes selected from the group consisting of KRT86, CRISPLD1, DSG1, SESN3, ADAMTS20, IRX1, SMC1B, CDKN2A, EFNB3, CXCL14, ZFR2, RNF212, MKRN3, SYCP2, MYL1, MYO3A, RNASE10, GALNT13, C19orf26, MUC4, PCDHGB1, CCND1, LCE1F, and KCNS1.
6. The method of claim 3 , wherein the discriminating gene set comprises KRT86, CRISPLD1, DSG1, SESN3, ADAMTS20, IRX1, SMC1B, CDKN2A, EFNB3, CXCL14, ZFR2, RNF212, MKRN3, SYCP2, MYL1, MYO3A, RNASE10, GALNT13, C19orf26, MUC4, PCDHGB1, CCND1, LCE1F, and KCNS1.
7. The method of claim 3 , wherein the dataset further comprises a variant allele count for TP53 (ENSG00000141510) and CDKN2A (ENSG00000147889) in the genome of the cancerous tissue from the subject.
8. The method of claim 1 , wherein the first therapy tailored for treatment of cervical cancer associated with an HPV infection comprises a therapeutic vaccine or an adoptive cell therapy.
9. The method of claim 8 , wherein the second therapy tailored for treatment of cervical cancer not associated with an HPV infection is a chemotherapy regimen.
10. The method of claim 9 , wherein the chemotherapy regimen comprises co-administration of cisplatin and a therapeutic agent selected from the group consisting of 5-fluorouracil, paclitaxel, and bevacizumab.
11. The method of claim 1 , wherein the second therapy tailored for treatment of cervical cancer not associated with an HPV infection is a chemotherapy regimen.
12. The method of claim 11 , wherein the chemotherapy regimen comprises co-administration of cisplatin and a second therapeutic agent selected from the group consisting of 5-fluorouracil, paclitaxel, and bevacizumab.
13. The method of claim 1 , wherein the classifier was trained by a method comprising:
(1) obtaining a dataset comprising, for each respective subject in a plurality of subjects of a species: (i) a corresponding plurality of abundance values, wherein each respective abundance value in the corresponding plurality of abundance values quantifies a level of expression of a corresponding gene, in a plurality of genes, in a tumor sample of the respective subject, and (ii) an indication of cancer condition of the respective subject, wherein the indication of cancer condition identifies whether the respective subject has the first cancer condition or the second cancer condition, and wherein the plurality of subjects includes a first subset of subjects that are afflicted with the first cancer condition and a second subset of subjects that are afflicted with the second condition;
(2) identifying the discriminating gene set using the corresponding plurality of abundance values and respective indication of the cancer condition of respective subjects in the plurality of subjects, wherein the discriminating gene set comprises a subset of the plurality of genes; and
(3) using the respective abundance values for the discriminating gene set and the respective indication of cancer condition across the plurality of subjects to train a classifier to discriminate between the first cancer condition and the second cancer condition as a function of respective abundance values for the discriminating gene set.