DETERMINATION OF SOURCE CONTRIBUTIONS USING BINOMIAL PROBABILITY CALCULATIONS
This invention relates to calculation of percent contribution of data from a major source and a minor source in a sample.
1 . A computer-implemented process for estimating a contribution of cell free nucleic acids from at least one of a major source and a minor source in a mixed sample, wherein at least one processor coupled to a memory executes a software component that performs the process, comprising:
accessing by the software component a first data set comprising frequency data for one or more informative loci from a major source;
accessing by the software component a second data set comprising frequency data for one or more informative loci from a minor source;
calculating by the software component an estimated contribution of cell free nucleic acids from the at least one of the major source and the minor source based on a binomial distribution of distinguishing regions from first and second data sets; and
outputting by the software component the estimated contribution of cell free nucleic acids from the at least one of the major source and the minor source.
2 . The process of claim 1 , wherein the mixed sample comprises cell free nucleic acids from both normal and putative genetically atypical cells.
3 . The process of claim 1 , wherein the mixed sample comprises cell free nucleic acids from two or more different organisms.
4 . The process of claim 1 , wherein the mixed sample comprises cell free nucleic acids from a donor cell source and a host recipient cell source.
5 . The process of claim 1 , wherein the software component quantifies the contribution by calculating the maximum likelihood estimate based on a quantity of the one or more informative loci from the major source and the minor source.
6 . The process of claim 5 , wherein the maximum likelihood estimate is modeled by the equation:
Binomial
(
A
,
B
,
p
)
=
(
A
+
B
)
!
A
!
B
!
p
A
(
1
-
p
)
B
wherein A is the quantity of an informative locus from the minor source, B is the quantity of an informative locus from the major source, and p is the maximum likelihood estimate for the binomial distribution with quantities A and B.
7 . The process of claim 6 , wherein the p corresponding to the maximum likelihood estimate is calculated using an optimization algorithm.
8 . The process of claim 5 , wherein frequency data for two or more informative loci from the major source and the minor source are used.
9 . The process of claim 8 , wherein the maximum likelihood estimate is modeled by the equation:
∏
i
Binomial
(
A
i
,
B
i
,
p
)
.
wherein A is the quantity of the informative loci from the minor source, B is the quantity of informative loci from the major source, and p is the maximum likelihood estimate for the binomial distribution with quantities A and B.
10 . The process of claim 9 , wherein the p corresponding to the maximum likelihood estimate is calculated using an optimization algorithm.
11 . A computer-implemented process for calculating a contribution of cell free nucleic acids from at least one of a minor source and major source in a mixed sample, wherein at least one processor coupled to a memory executes a software component that performs the process, comprising:
accessing by the software component a first data set comprising frequency data based on identification of distinguishing regions of one or more major source informative loci in the sample;
accessing by the software component a second data set comprising frequency data based on identification of distinguishing regions of one or more minor source informative loci in the sample;
calculating by the software component an estimated contribution of cell free nucleic acids from the at least one of the minor source and the major source based on a binomial distribution of the counts of distinguishing regions from first and second data sets; and
outputting by the software component the estimated contribution of cell free nucleic acids from the at least one of the major source and the minor source.
12 . The process of claim 11 , wherein the mixed sample comprises cell free nucleic acids from both normal and putative genetically atypical cells.
13 . The process of claim 11 , wherein the mixed sample comprises cell free nucleic acids from two or more different organisms.
14 . The process of claim 11 , wherein the mixed sample comprises cell free nucleic acids from a donor cell source and a host recipient cell source.
15 . The process of claim 11 , wherein the distinguishing regions comprise single nucleotide polymorphisms.
16 . The process of claim 11 , wherein the distinguishing regions comprise differences in methylation.
17 . The process of claim 11 , wherein the distinguishing regions comprise short tandem repeats.
18 . The process of claim 11 , wherein software component quantifies the contribution by calculating the maximum likelihood estimate based on the quantity of the informative loci from the major source and the minor source.
19 . The process of claim 18 , wherein the maximum likelihood estimate is modeled by the equation:
Binomial
(
A
,
B
,
p
)
=
(
A
+
B
)
!
A
!
B
!
p
A
(
1
-
p
)
B
wherein A is the quantity of an informative locus from the minor source, B is the quantity of an informative locus from the major source, and p is the maximum likelihood estimate for the binomial distribution with quantities A and B.
20 . The process of claim 19 , wherein the p corresponding to the maximum likelihood estimate is calculated using an optimization algorithm.
21 . The process of claim 18 , wherein frequency data for two or more informative loci from the major source and the minor source are used.
22 . The process of claim 21 , wherein the maximum likelihood estimate is modeled by the equation:
∏
i
Binomial
(
A
i
,
B
i
,
p
)
.
wherein A is the quantity of the informative loci from the minor source, B is the quantity of informative loci from the major source, and p is the maximum likelihood estimate for the binomial distribution with quantities A and B.
23 . The process of claim 22 , wherein the p corresponding to the maximum likelihood estimate is calculated using an optimization algorithm.
24 . A computer-implemented process for calculating a contribution of cell free nucleic acids from a maternal major source and a fetal minor source in a maternal sample, wherein at least one processor coupled to a memory executes a software component that performs the process, comprising:
accessing by the software component a first data set comprising frequency data based on identification of distinguishing regions from copies of one or more informative loci from the maternal major source;
accessing by the software component a second data set comprising frequency data based on identification of distinguishing regions from copies of one or more informative loci from the fetal minor source;
calculating by the software component an estimated contribution of cell free nucleic acids from the at least one of the maternal source and the fetal source based on a binomial distribution of the counts of the distinguishing regions from first and second data sets; and
outputting by the software component the estimated contribution of cell free nucleic acids from the at least one of the maternal major source and a fetal minor source.
25 . The process of claim 24 , wherein the distinguishing regions comprise single nucleotide polymorphisms.
26 . The process of claim 24 , wherein the distinguishing regions comprise differences in methylation.
27 . The process of claim 24 , wherein the distinguishing regions comprise short tandem repeats.
28 . The process of claim 24 , wherein the software component quantifies the contribution by calculating the maximum likelihood estimate based on the quantity of the informative loci from the major source and the minor source.
29 . The process of claim 28 , wherein the contribution is modeled by the equation:
Binomial
(
A
,
B
,
p
)
=
(
A
+
B
)
!
A
!
B
!
p
A
(
1
-
p
)
B
.
wherein A is the count of informative loci from the minor source, B is the is the count of informative loci from the major source, and p is the maximum likelihood estimate for the binomial distribution with quantities A and B.
30 . The process of claim 29 , wherein the p corresponding to the maximum likelihood estimate is calculated using an optimization algorithms.
31 . The process of claim 28 wherein frequency data for two or more informative loci from the major source and the minor source are used.
32 . The process of claim 28 , wherein the maximum likelihood estimate is modeled by the equation:
∏
i
Binomial
(
A
i
,
B
i
,
p
)
.
wherein A is the quantity of the informative loci from the minor source, B is the quantity of informative loci from the major source, and p is the maximum likelihood estimate for the binomial distribution with quantities A and B.
33 . The process of claim 32 , wherein the p corresponding to the maximum likelihood estimate is calculated using an optimization algorithm.
34 . An executable software product stored on a computer-readable medium containing program instructions for estimating nucleic acid contribution in a mixed sample, the program instructions for:
inputting a first data set comprising frequency data based on identification of distinguishing regions from copies of one or more informative loci from a major source;
inputting a second data set frequency data based on identification of distinguishing regions from copies of one or more informative loci from a minor source; and
calculating a percent contribution of cell free nucleic acids from at least one of the major source and the minor source based on a binomial distribution of the first and second data sets.
35 . A system, comprising:
a memory;
a processor coupled to the memory; and
a software component executed by the processor that is configured to:
receive a first data set comprising the frequency data based on identification of distinguishing regions from copies of one or more informative loci from a major source;
receive a second data set comprising the frequency data based on identification of distinguishing regions from copies of one or more informative loci from a minor source; and
calculate a percent contribution of cell free nucleic acids from at least one of the major source and the minor source based on a binomial distribution of the first and second data sets.
36 . A computer software product including a non-transitory computer-readable storage medium having fixed therein a sequence of instructions which when executed by a computer direct performance of steps of:
creating a first data set representing a quantity of informative loci from a minor source in a mixed sample;
creating a second data set representing a quantity of informative loci from a major source in the mixed sample; and
calculating a percent contribution of cell free nucleic acids from at least one of the major source and the minor source based on a binomial distribution of distinguishing regions from first and second data sets.