Personalized genetic testing

Abstract

The present disclosure provides methods and systems for personalized genetic testing of a subject. In some embodiments, a sequencing assay is performed on a biological sample from the subject, which then leads to genetic information related to the subject. Next, nucleic acid molecules are array-synthesized or selected based on the genetic information derived from data of the sequencing assay. At least some of the nucleic acid molecules may then be used in an assay which may provide additional information on one or more biological samples from the subject or a biological relative of the subject.

1 .- 30 . (canceled) 
     
     
         31 . A method for personalized genetic testing, comprising:
 (a) obtaining sequencing data derived from nucleic acid molecules of at least one biological sample of at least one subject, wherein said sequencing data comprises: (i) sequence information for an exome, a panel of genes, a whole genome, or a population of complementary deoxyribonucleic acid (cDNA) molecules derived from ribonucleic acids (RNA) of said at least one subject and (ii) at least one set of genetic variants identified in said exome, said panel of genes, said whole genome, or said population of cDNA molecules derived from RNA of said at least one subject;   (b) using a personalized probe set, selectively enriching nucleic acid sequences comprising said at least one set of genetic variants over other sequences in at least one additional biological sample from said at least one subject, to generate a sequencing library, wherein said probe set is configured to selectively enrich nucleic acid sequences comprising said at least one set of genetic variants over other sequences in said at least one biological sample of said at least one subject; and   (c) subjecting said sequencing library to sequencing to identify a presence or absence of at least a subset of said at least one set of genetic variants in said at least one additional biological sample from said at least one subject, wherein a sequencing depth of said sequencing of (c) is greater than a sequencing depth of said sequencing of (a).   
     
     
         32 . The method of  claim 31 , wherein said nucleic acid array comprises at least 55,000 nucleic acid probes. 
     
     
         33 . The method of  claim 31 , wherein said nucleic acid array comprises less than 55,000 nucleic acid probes. 
     
     
         34 . The method of  claim 31 , wherein said personalized probe set comprises at least 200 probes. 
     
     
         35 . The method of  claim 31 , wherein said at least one set of genetic variants comprises at least 200 genetic variants. 
     
     
         36 . The method of  claim 31 , wherein said personalized probe set comprises hybrid capture probes. 
     
     
         37 . The method of  claim 31 , wherein said at least one subject is a plurality of subjects, and wherein said at least one biological sample is a plurality of samples, to yield a multiplexed assay. 
     
     
         38 . The method of  claim 37 , wherein said personalized probe set comprises barcode sequences, wherein a barcode sequence corresponds to a biological sample from the plurality of biological samples or a subject from the plurality of subjects, respectively. 
     
     
         39 . The method of  claim 37 , wherein said multiplexed assay is demultiplexed by (i) hybridization to a nucleic acid array using nucleic acid barcodes incorporated into the array-synthesized sequences, (ii) PCR using primers incorporated into the array-synthesized sequences, (iii) electrophoresis, or (iv) mass spectroscopy. 
     
     
         40 . The method of  claim 31 , wherein said at least one set of genetic variants comprises one or more locations in or regions of a genome or portions thereof, and wherein said selective enriching of (b) comprises the depletion of locations or regions of the genome or portions thereof. 
     
     
         41 . The method of  claim 40 , wherein said locations or regions of the genome or portions thereof comprise modified nucleotides including methylated nucleotides or nucleotide analogs. 
     
     
         42 . The method of  claim 31 , wherein said at least one biological sample in (a) was obtained at substantially the same time as said at least one additional biological sample in (c). 
     
     
         43 . The method of  claim 31 , wherein said at least one biological sample in (a) and said at least one additional biological sample in (c) were derived from the same blood sample, buccal swab or tumor biopsy. 
     
     
         44 . The method of  claim 31 , wherein said at least one biological sample in (a) or (c) comprises cell-free nucleic acid molecules. 
     
     
         45 . The method of  claim 44 , wherein said cell-free nucleic acid molecules comprise circulating tumor nucleic acid molecules. 
     
     
         46 . The method of  claim 31 , wherein said at least one biological sample in (a) or (c) comprises nucleic acid molecules from a tumor biopsy. 
     
     
         47 . The method of  claim 31 , further comprising obtaining additional biological samples at one or more later timepoints. 
     
     
         48 . The method of  claim 31 , wherein said at least one biological sample in (a) comprises nucleic acid molecules from a tumor biopsy and wherein said at least one additional biological sample in (c) comprises cell-free nucleic acid molecules from blood and/or plasma. 
     
     
         49 . The method of  claim 31 , wherein said personalized probe set comprises at least one variable portion based on said sequence data of (a) and at least one fixed portion that is independent of said sequence data of (a). 
     
     
         50 . The method of  claim 31 , wherein said personalized probe set comprises nucleic acid barcodes. 
     
     
         51 . The method of  claim 31 , further comprising, in (b), computer processing said sequencing data to identify a plurality of genetic characteristics of said subject comprising levels of gene expression, sequence counts, or read-depth in said sequencing data generated from ribonucleic acid molecules or cDNA molecules derived from said at least one biological sample. 
     
     
         52 . The method of  claim 31 , wherein said personalized probe set comprises sequences configured to selectively enrich nucleic acids comprising V(D)J sequences derived from T-cells or B-cells of said subject. 
     
     
         53 . The method of  claim 52 , wherein said sequence data comprises sequence information derived from T-Cell repertoire nucleic acid sequences or B-Cell repertoire nucleic acid sequences. 
     
     
         54 . The method of  claim 53 , wherein said sequence data comprises sequence information derived from: (i) said T-Cell repertoire nucleic acids sequences or said B-Cell repertoire nucleic acid sequences and (ii) tumor nucleic acid sequences. 
     
     
         55 . The method of  claim 31 , wherein said personalized probe set comprises sequences configured to selectively enrich sequences of one or more pathogen-derived nucleic acid molecules. 
     
     
         56 . The method of  claim 55 , wherein said one or more pathogen-derived nucleic acid molecules are derived from a pathogen selected from the group consisting of: a virus, a fungus, a bacterium, a protozoan, and any combination thereof. 
     
     
         57 . The method of  claim 31 , wherein said probe set comprises sequences configured to selectively enrich one or more viral sequences. 
     
     
         58 . The method of  claim 57 , wherein said one or more viral sequences are derived from a virus selected from the group consisting of: adenovirus, coxsackievirus, Epstein-Barr virus, Hepatitis virus, herpes simplex virus (type 1 and 2), cytomegalovirus, herpes virus, HIV, influenza virus, measles virus, mumps virus, papillomavirus, parainfluenza virus, poliovirus, respiratory syncytial virus, rubella virus, varicella-zoster virus, and any combination thereof. 
     
     
         59 . The method of  claim 31 , wherein said personalized probe set comprises sequences configured to selectively enrich sequences of fetal mutations or genetic abnormalities. 
     
     
         60 . The method of  claim 31 , further comprising synthesizing said personalized probe set.