# US 2024/0200136 A1 · Methods and systems for genetic analysis

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- Number: US 2024/0200136 A1
- Document ID: US20240200136A1
- Status: Published application
- Kind: A1
- Application number: 18/593,406
- Filed: 2024-03-01
- Published: 2024-06-20
- Earliest claimed: 2016-05-27
- Assignees: Personalis, Inc.
- Applicants: Personalis, Inc.
- Inventors: John West; Christian Haudenschild; Richard Chen
- Web page: https://patentgrep.com/patent/US20240200136A1

## CPC

- C12Q 1/6874: involving nucleic acid arrays, e.g. sequencing by hybridisation
- C12Q 1/6806: Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay (C12Q1/6804 takes precedence)
- G16B 20/00: ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
- G16B 20/10: Ploidy or copy number detection
- G16B 20/20: Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
- G16B 30/00: ICT specially adapted for sequence analysis involving nucleotides or amino acids
- G16B 35/10: Design of libraries
- G16B 99/00: Subject matter not provided for in other groups of this subclass
- C12Q 1/6869: Methods for sequencing
- G16B 35/00: ICT specially adapted for in silico combinatorial libraries of nucleic acids, proteins or peptides
- G16C 20/60: In silico combinatorial chemistry
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- G16B: BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
- G16C: COMPUTATIONAL CHEMISTRY; CHEMOINFORMATICS; COMPUTATIONAL MATERIALS SCIENCE

## Abstract

This disclosure provides systems and methods for sample processing and data analysis. Sample processing may include nucleic acid sample processing and subsequent sequencing. Some or all of a nucleic acid sample may be sequenced to provide sequence information, which may be stored or otherwise maintained in an electronic storage location. The sequence information may be analyzed with the aid of a computer processor, and the analyzed sequence information may be stored in an electronic storage location that may include a pool or collection of sequence information and analyzed sequence information generated from the nucleic acid sample. Methods and systems of the present disclosure can be used, for example, for the analysis of a nucleic acid sample, for producing one or more libraries, and for producing biomedical reports. Methods and systems of the disclosure can aid in the diagnosis, monitoring, treatment, and prevention of one or more diseases and conditions.

## Claims

### Claim at position 1

1-20. (canceled)

### Claim 21

A method for personalized genetic testing, comprising:
(a) performing a first assay on nucleic acid molecules extracted from at least one biological sample from a subject to produce a first set of nucleic acid sequence data, wherein:
(i) the at least one biological sample comprises a tumor sample from the subject,
(ii) the first assay comprises whole genome sequencing, and
(iii) the whole genome sequencing comprises sequencing by synthesis;
(b) extracting a set of one or more genetic characteristics from the first set of nucleic acid sequence data by aligning the first set of nucleic acid sequence data to a reference genome, wherein the reference genome is from the subject;
(c) aggregating the set of one or more genetic characteristics to generate a signature of the subject;
(d) obtaining a personalized probe set for the subject, wherein the personalized probe set comprises the signature of aggregating step (c) or complements thereof;
(e) performing a second assay on nucleic acid molecules extracted from one or more plasma samples from the subject using a microarray to obtain a second set of nucleic acid sequence data, wherein the microarray comprises the personalized probe set; and
(f) outputting biomedical information of the subject based on an analysis comparing results from the first assay with results from the second assay.

### Claim 22 (depends on 21)

The method of claim 21, wherein the personalized probe set further comprises at least one fixed portion independent of the results of the first assay.

### Claim 23 (depends on 21)

The method of claim 21, wherein the obtaining of step (d) comprises printing the personalized probe set onto a surface of the microarray.

### Claim 24 (depends on 23)

The method of claim 23, wherein printing comprises contact printing or non-contact printing.

### Claim 25 (depends on 24)

The method of claim 24, wherein the printing comprises contact printing, and the contact printing comprises directly applying a probe solution comprising nucleic acid(s) onto the microarray surface using one or more print pins.

### Claim 26 (depends on 24)

The method of claim 24, wherein the printing comprises noncontact printing, and the noncontact printing comprises expelling small droplets of a probe solution comprising nucleic acid(s) onto the microarray surface using a bubble jet or an inkjet.

### Claim 27 (depends on 24)

The method of claim 24, wherein the personalized probe set further comprises at least one fixed portion independent of the results of the first assay.

### Claim 28 (depends on 21)

The method of claim 21, wherein the nucleic acid molecules extracted from the tumor sample comprise: (i) DNA, (ii) RNA, or (iii) cDNA derived from RNA.

### Claim 29 (depends on 21)

The method of claim 21, wherein the nucleic acid molecules extracted from the one or more plasma samples comprise: (i) DNA, (ii) RNA, (iii) cDNA derived from RNA, (iv) cfDNA, or (v) cfRNA.

### Claim 30 (depends on 21)

The method of claim 21, wherein the set of one or more genetic characteristics comprises: (i) Single Nucleotide Polymorphisms (SNPs), (ii) Multiple Nucleotide Polymorphisms (MNPs), (iii) insertions and/or deletions (inDels), (iv) copy number variations, (v) structural variations, (vi) HLA typing, or any combination thereof.

### Claim 31 (depends on 21)

The method of claim 21, wherein the at least one biological sample comprises a plurality of biological samples.

### Claim 32 (depends on 31)

The method of claim 31, wherein the plurality of biological samples comprises the tumor sample of step (a)(i) and a sample reflective of the germline genome of the subject.

### Claim 33 (depends on 32)

The method of claim 32, wherein the sample reflective of the germline genome of the subject comprises white blood cells.

### Claim 34 (depends on 32)

The method of claim 32, wherein the nucleic acid molecules extracted from the plurality of biological samples comprise: (i) DNA, (ii) RNA, or (iii) cDNA derived from RNA.

### Claim 35 (depends on 32)

The method of claim 32, wherein the set of one or more genetic characteristics comprises: (i) Single Nucleotide Polymorphisms (SNPs), (ii) Multiple Nucleotide Polymorphisms (MNPs), (iii) insertions and/or deletions (inDels), (iv) copy number variations, (v) structural variations, (vi) mosaic variants, (vii) somatic variants, (viii) HLA typing, (ix) V(D)J recombination, or any combination thereof.

### Claim 36 (depends on 21)

The method of claim 21, wherein the at least one biological sample is obtained at a first time point and the one or more plasma samples are obtained at one or more time points subsequent to the first time point.

### Claim 37 (depends on 21)

The method of claim 21, wherein the biomedical information comprises a biomedical report.

### Claim 38 (depends on 37)

The method of claim 37, wherein the biomedical report comprises reporting: (i) information of the subject that is predictive, prognostic, or diagnostic of one or more biomedical features, (ii) information of the subject that is predictive, prognostic, or diagnostic of a status or outcome of a disease or condition in the subject, or (iii) one or more biomedical outputs.

### Claim 39 (depends on 38)

The method of claim 38, wherein the one or more biomedical features comprise: (i) status of a disease or condition, (ii) genetic risk of a disease or condition, (iii) risk of an adverse drug reaction, (iv) efficacy of a drug therapy, (v) prediction of optimal drug dosage, (vi) transplant tolerance, or a combination thereof.

### Claim 40 (depends on 39)

The method of claim 39, wherein the disease or condition comprises cancer.

### Claim 41 (depends on 40)

The method of claim 40, wherein the cancer comprises recurrent cancer and/or refractory cancer.

### Claim 42 (depends on 40)

The method of claim 40, wherein the cancer comprises a sarcoma, a carcinoma, a lymphoma, or a leukemia.

### Claim 43 (depends on 38)

The method of claim 38, wherein the predictive, prognostic, or diagnostic information of the biomedical report comprises a member selected from the group consisting of: (i) diagnosing a disease or condition, (ii) identifying a disease or condition, (iii) determining stage of a disease or condition, (iv) assessing risk of a disease or condition, (v) assessing risk of disease recurrence, (vi) assessing efficacy of a drug, (vii) assessing risk of an adverse drug reaction, (viii) predicting optimal drug dosage, and (ix) predicting drug resistance.

### Claim 44 (depends on 43)

The method of claim 43, wherein the disease or condition comprises cancer.

### Claim 45 (depends on 44)

The method of claim 44, wherein the cancer comprises recurrent cancer and/or refractory cancer.

### Claim 46 (depends on 44)

The method of claim 44, wherein the cancer comprises a sarcoma, a carcinoma, a lymphoma, or a leukemia.

### Claim 47 (depends on 38)

The method of claim 38, wherein the one or more biomedical outputs suggest, select, designate, recommend, or otherwise determine a course of treatment and/or prevention of a disease or condition.

### Claim 48 (depends on 38)

The method of claim 38, wherein the one or more biomedical outputs recommend modifying or continuing one or more therapies.

### Claim 49 (depends on 48)

The method of claim 48, wherein modifying one or more therapies comprises administering, initiating, reducing, increasing, and/or terminating one or more therapies.

### Claim 50 (depends on 49)

The method of claim 49, wherein the one or more therapies comprise an anticancer therapy, wherein the anticancer therapy comprises surgery, chemotherapy, radiation therapy, immunotherapy/biological therapy, photodynamic therapy, monoclonal antibodies, cancer vaccines, gene therapy, or a combination thereof.