Methods and Systems for Medical Sequencing Analysis
First Claim
1. A method of identifying an inherited trait in a subject, comprisingcollecting a biological sample from the subject comprising a DNA sequence;
- aligning the DNA sequence to normal reference sequences and mutant reference sequences;
counting sequence reads aligning to normal references;
counting sequence reads aligning to mutant references; and
determining a ratio of aligned reads, wherein if the ratio is greater than a first value the inherited trait is a homozygous mutant, if the ratio is between a second value and a third value the inherited trait is a heterozygous mutant, and if the ratio is less than a fourth value the inherited trait is a homozygous wild-type.
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Accused Products
Abstract
Disclosed are methods of identifying elements associated with a trait, such as a disease. The methods can comprise, for example, identifying the association of a relevant element (such as a genetic variant) with a relevant component phenotype (such as a disease symptom) of the trait, wherein the association of the relevant element with the relevant component phenotype identifies the relevant element as an element associated with the trait, wherein the relevant component phenotype is a component phenotype having a threshold value of severity, age of onset, specificity to the trait or disease, or a combination, wherein the relevant element is an element having a threshold value of importance of the element to homeostasis relevant to the trait, intensity of the perturbation of the element, duration of the effect of the element, or a combination. The disclosed methods are based on a model of how elements affect complex diseases. The disclosed model is based on the existence of significant genetic and environmental heterogeneity in complex diseases. Thus, the specific combinations of genetic and environmental elements that cause disease vary widely among the affected individuals in a cohort. The disclosed model is an effective, general experimental design and analysis approach for the identification of causal variants in common, complex diseases by medical sequencing. Also disclosed herein are methods of identifying an inherited trait in a subject. The disclosed methods compare a reference sequence from a subject to a library of sequences that contain each mutation. For a given mutation, a normal sequence read aligns best to the normal library sequence. A read having the mutation aligns best to the mutant library sequence. The disclosed model and the disclosed methods based on the model can be used to generate valuable and useful information.
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Citations
20 Claims
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1. A method of identifying an inherited trait in a subject, comprising
collecting a biological sample from the subject comprising a DNA sequence; -
aligning the DNA sequence to normal reference sequences and mutant reference sequences; counting sequence reads aligning to normal references; counting sequence reads aligning to mutant references; and determining a ratio of aligned reads, wherein if the ratio is greater than a first value the inherited trait is a homozygous mutant, if the ratio is between a second value and a third value the inherited trait is a heterozygous mutant, and if the ratio is less than a fourth value the inherited trait is a homozygous wild-type. - View Dependent Claims (2)
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3. A method of determining a status of a subject with regard to an inherited trait comprising:
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assaying an element from a sample from a subject to determine a subject DNA sequence; comparing the subject DNA sequence to a set of DNA sequences by alignment wherein the set of DNA sequences comprises both normal, unaffected DNA sequences and mutated, variant DNA sequences; identifying the element as being associated with the inherited trait by the coincidence of the element and the trait within the sample by determining a ratio of the subject DNA sequence that matches normal, unaffected DNA sequences and the mutated variant DNA sequences. - View Dependent Claims (4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16)
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17. A system for identifying an inherited trait in a subject, comprising
a memory; - and
a processor, coupled to the memory, configured for, collecting a biological sample from the subject comprising a DNA sequence, aligning the DNA sequence to normal reference sequences and mutant reference sequences, counting sequence reads aligning to normal references, counting sequence reads aligning to mutant references, and determining a ratio of aligned reads, wherein if the ratio is greater than a first value the inherited trait is a homozygous mutant, if the ratio is between a second value and a third value the inherited trait is a heterozygous mutant, and if the ratio is less than a fourth value the inherited trait is a homozygous wild-type. - View Dependent Claims (18, 19, 20)
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Specification