Resolving genome fractions using polymorphism counts

An apparatus for estimating a fraction of fetal DNA in DNA obtained from a bodily fluid of a pregnant individual carrying a fetus, the apparatus comprising system memory and one or more processors configured to:

• sequence DNA extracted from a sample of the bodily fluid comprising DNA of both a maternal genome and a fetal genome to produce DNA sequence reads containing a plurality of polymorphisms;
• map the DNA sequence reads to a plurality of polymorphism sites on a reference sequence corresponding to the plurality of polymorphisms;
• determine allele frequencies of the mapped DNA sequence reads for the plurality of polymorphisms;
• and
• apply the allele frequencies to a mixture model to estimate the fraction of fetal DNA in the DNA obtained from the bodily fluid of the individual carrying the fetus.

A computer program product comprising a non-transitory machine readable medium storing program code that, when executed by one or more processors of a computer system, causes the computer system to implement a method of estimating a fraction of fetal DNA in DNA obtained from a bodily fluid of a pregnant individual carrying a fetus, said program code comprising:

• (a) code for sequencing DNA obtained from the bodily fluid of the pregnant individual using a nucleic acid sequencer under conditions that produce DNA sequence reads containing a plurality of polymorphisms;
• (b) code for mapping the DNA sequence reads to a plurality of polymorphism sites on a reference sequence corresponding to the plurality of polymorphisms;
• (c) code for determining allele frequencies of the DNA sequence reads for the plurality of polymorphisms;
• and
• (d) code for applying the allele frequencies to a mixture model to estimate the fraction of fetal DNA in the DNA obtained from the bodily fluid of the individual carrying the fetus, wherein the mixture model employs factorial moments to calculate the fraction of fetal DNA.