Method and System for DNA Mixture Analysis

Abstract

The present invention pertains to a process for automatically analyzing mixed DNA samples. Specifically, the process comprises the steps of obtaining a mixed DNA sample; amplifying the DNA sample to produce a product; detecting the product to produce a signal; and analyzing the signal to determine information about the composition of the mixed DNA sample. This DNA mixture analysis is useful for finding criminals and convicting them. This mixture analysis provides high quality estimates, and can determine genotypes, mixture weights, and likelihood ratios. This analysis provides confidence measures in the results it computes, and generates reports and intuitive visualizations. The process automates a tedious manual procedure, thereby reducing the cost, time, and effort involved in DNA forensic analysis. The system can greatly accelerate the rate of DNA crime analysis, and be used to exonerate innocent people.

What is claimed is: 
     
         1 . A method of analyzing a biological sample comprised of the steps:
 (a) obtaining a biological sample that contains DNA;   (b) amplifying the DNA to produce a product;   (c) detecting the product to generate data, where the data can be explained by more than one genotype value;   (d) assuming a genotype value which is stored in a nontransient memory; and   (e) determining a likelihood using a computer in communication with the memory, where the likelihood is defined as a probability of observing the detected data, and said probability is conditioned on the genotype value and other parameters.   
     
     
         2 . A method as described in  claim 1  where after the determining step there is the step of computing a probability of the genotype value using the determined likelihood. 
     
     
         3 . A method as described in  claim 1  where after the determining step there is the step of calculating a likelihood ratio of a hypothesis using the determined likelihood. 
     
     
         4 . A method as described in  claim 1  where the determined likelihood includes as a conditional parameter a number of contributors to the biological sample. 
     
     
         5 . A method as described in  claim 1  where the determined likelihood accounts for DNA amplification artifacts. 
     
     
         6 . A method as described in  claim 1  where the genotype relates to a short tandem repeat (STR) genetic locus. 
     
     
         7 . A method as described in  claim 1  where the genotype relates to a single nucleotide polymorphism (SNP) genetic locus. 
     
     
         8 . A method as described in  claim 1  where the biological sample is a mixture of DNA from two or more individuals. 
     
     
         9 . A method as described in  claim 1  where the amplification step is repeated to obtain additional data for determining the likelihood. 
     
     
         10 . A method as described in  claim 5  where the artifact is polymerase chain reaction (P CR) stutter. 
     
     
         11 . A method as described in  claim 5  where the artifact is relative amplification. 
     
     
         12 . A method as described in  claim 1  where after the determining step there is the step of calculating a likelihood ratio for two different hypotheses using the determined likelihood. 
     
     
         13 . A method as described in  claim 3  where the hypothesis is that an individual has contributed their DNA to the biological sample. 
     
     
         14 . A method as described in  claim 2  where genotype probability is computed for all feasible genotype values to form a genotype probability distribution. 
     
     
         15 . A method as described in  claim 14  where the genotype probability distribution corresponds to an individual who contributed their DNA to the biological sample. 
     
     
         16 . A method of storing genotypes of biological samples on a database comprised of the steps:
 (a) obtaining a biological sample that contains DNA;   (b) amplifying the DNA to produce a product;   (c) detecting the product to generate data, where the data can be explained by more than one genotype value;   (d) assuming a genotype value which is stored in a nontransient memory;   (e) determining a likelihood using a computer in communication with the memory, where the likelihood is defined as a probability of observing the detected data, and said probability is conditioned on the genotype value and other parameters;   (f) computing a probability of the genotype value using the determined likelihood;   (g) inferring a genotype for a contributor to the biological evidence, where the genotype is a probability distribution over genotype values; and   (h) uploading the genotype to a database of genotypes.   
     
     
         17 . A method as described in  claim 16  where after the uploading step there is the further step of comparing genotypes to genotypes on the database. 
     
     
         18 . A method as described in  claim 17  where after the comparing step there is the further step of downloading genotype comparisons from the database. 
     
     
         19 . A method as described in  claim 17  where the genotype comparison identifies an investigative lead between biological samples. 
     
     
         20 . A method of securely transmitting a signal comprised of the steps:
 (a) obtaining a genotype;   (b) deriving an encryption key from the genotype;   (c) specifying a message comprised of text;   (d) encoding the message as a mixed signal of the text together with the encryption key;   (e) securely transmitting the encoded message as the mixed signal; and   (f) decoding the message from the mixed signal using the encryption key derived from the genotype.