Detection and treatment of disease exhibiting disease cell heterogeneity and systems and methods for communicating test results

A diseased cell and heterogeneity technology, applied in biochemical equipment and methods, microbiological determination/testing, sequence analysis, etc., can solve problems such as reducing the quality of care for cancer patients

Active Publication Date: 2017-11-28
GUARDANT HEALTH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Some physicians have difficulty interpreting probabilistic data related to the clinical use of diagnostic tests, such as the positive or negative predictive value of laboratory tests
[0008] Error rates and biases in detecting cancer-associated de novo genomic alterations and inadequate genetic testing for cancer explain or imply reduced quality of care for cancer patients

Method used

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  • Detection and treatment of disease exhibiting disease cell heterogeneity and systems and methods for communicating test results
  • Detection and treatment of disease exhibiting disease cell heterogeneity and systems and methods for communicating test results
  • Detection and treatment of disease exhibiting disease cell heterogeneity and systems and methods for communicating test results

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0239] Example 1. Copy number variation detection method

[0240] blood collection

[0241] A 10-30 mL blood sample was collected at room temperature. Samples were centrifuged to remove cells. Plasma was collected after centrifugation.

[0242] cfDNA extraction

[0243] Samples were digested with proteinase K. Precipitate DNA with isopropanol. DNA was captured on a DNA purification column (eg, QIAamp DNABlood Mini Kit) and eluted in 100 μl of the solution. DNA below 500bp was selected by Ampure SPRI magnetic bead capture (PEG / salt). The resulting product was suspended in 30 μl HO 2O middle. The size distribution was examined (major peak = 166 nucleotides; minor peak = 330 nucleotides) and quantified. 5 ng of extracted DNA contained approximately 1700 haploid genome equivalents ("HGE"). The general relationship between the amount of DNA and HGE is as follows: 3 pg DNA = 1 HGE; 3 ng DNA = 1K HGE; 3 μg DNA = 1 M HGE; 10 pg DNA = 3HE; 10 ng DNA = 3K HGE;

[0244] ...

Embodiment 2

[0256] Example 2. Method of Correcting Base Calls by Determining the Total Number of Undiscovered Molecules in a Sample

[0257] After the fragments are amplified and the sequences of the amplified fragments are read and compared, the fragments are base called. Variation in the number of amplified fragments and undiscovered amplified fragments may introduce errors in base calling. These variations were corrected for by counting the number of amplified fragments not found.

[0258] When performing base calling on locus A (arbitrary locus), it is first assumed that there are N amplified fragments. Sequence reads may come from two types of fragments: double-stranded fragments and single-stranded fragments. The following is a theoretical example of calculating the total number of molecules not found in a sample.

[0259] N is the total number of molecules in the sample.

[0260] Assume that the number of duplexes detected is 1000.

[0261] Assume that the number of detected...

Embodiment 3

[0283] Example 3. Identification of genetic variants among cancer-associated somatic variants in patients

[0284] The assay is used to analyze a panel of genes to identify genetic variants in cancer-associated somatic variants with high sensitivity.

[0285] Cell-free DNA is extracted from the patient's plasma and amplified by PCR. Genetic variants are analyzed by massively parallel sequencing of amplified target genes. For a panel of genes, all exons were sequenced, as such sequencing coverage has been shown to have clinical utility (Table 3). For another set of genes, sequencing coverage included those exons with previously reported somatic mutations (Table 4). The smallest detectable mutant allele (limit of detection) depends on the patient's sample cell-free DNA concentration, which varies from less than 10 to more than 1,000 genome equivalents per mL of peripheral blood. In samples with lower amounts of cell-free DNA and / or low levels of gene copy amplification, amp...

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Abstract

This disclosure provides, among other things, methods for generating and applying therapeutic interventions. The methods involve, for example, (a) sequencing polynucleotides from cancer cells from a subject; (b) identifying and quantifying somatic mutations in the polynucleotides; (c) developing a profile of tumor heterogeneity in the subject indicating the presence and relative quantity of a plurality of the somatic mutations in the polynucleotides, wherein different relative quantities indicates tumor heterogeneity; and (d) determining a therapeutic intervention for a cancer exhibiting the tumor heterogeneity, wherein the therapeutic intervention is effective against a cancer having the profile of tumor heterogeneity determined.

Description

[0001] Cross References to Related Applications [0002] This application claims the benefit of U.S. Provisional Application No. 62 / 098,426, filed December 31, 2014, and U.S. Provisional Application No. 62 / 155,763, filed May 1, 2015, each of which is filed by Incorporated by reference in its entirety. Background technique [0003] Healthcare is only now beginning to effectively use information from the human genome to diagnose and treat disease. Nothing is more important than curing cancer, which kills 7.6 million people in the United States every year and spends $87 billion a year on cancer treatment in the United States. Cancer refers to the various malignant neoplasms characterized by the proliferation of degenerative cells prone to invade surrounding tissues and metastasize to new body sites, as well as any disorder characterized by the pathology of such growth. [0004] One of the reasons cancer is so difficult to treat is that current testing methods may not help doct...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/68C12N15/11G16B30/00
CPCC12Q1/6827C12Q2600/156C12Q1/6869G16B30/00C12Q1/6886C12Q2535/113C12Q2545/114C12Q2527/113C12Q2535/122C12Q2537/149C12Q2537/165C12N15/11C12Q2600/118
Inventor 埃尔米·埃尔图凯阿米尔阿里·塔拉萨兹巴赫拉姆·加法尔扎德·克曼尼纳姆迪·伊胡埃格布
Owner GUARDANT HEALTH
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