SYSTEM AND METHOD FOR CLEANING NOISY GENETIC DATA FROM TARGET INDIVIDUALS USING GENETIC DATA FROM GENETICALLY RELATED INDIVIDUALS
A system and method for determining the genetic data for one or a small set of cells, or from fragmentary DNA, where a limited quantity of genetic data is available, are disclosed. Genetic data for the target individual is acquired and amplified using known methods, and poorly measured base pairs, missing alleles and missing regions are reconstructed using expected similarities between the target genome and the genome of genetically related subjects. In accordance with one embodiment of the invention, incomplete genetic data is acquired from embryonic cells, fetal cells, or cell-free fetal DNA isolated from the mother's blood, and the incomplete genetic data is reconstructed using the more complete genetic data from a larger sample diploid cells from one or both parents, with or without genetic data from haploid cells from one or both parents, and/or genetic data taken from other related individuals.
1 . A method for determining genetic data for DNA from cancer cells, the method comprising:
isolating cell-free DNA from a biological sample and amplifying a plurality of target loci from the isolated cell-free DNA to obtain amplification products;
sequencing the amplification products by sequencing-by-synthesis to obtain genetic data for the plurality of target loci; and
determining the most likely genetic data for DNA from cancer cells based on the genetic data.
2 . The method of claim 1 , wherein the biological sample is a blood sample.
3 . The method of claim 1 , wherein the amplification comprises targeted amplification to amplify the target loci.
4 . The method of claim 1 , wherein the amplification further comprises universal amplification.
5 . The method of claim 1 , wherein the sequencing-by-synthesis comprises clonal amplification and measurement of sequences of the clonally amplified DNA.
6 . The method of claim 1 , wherein the target loci comprise SNP loci.
7 . The method of claim 6 , wherein the confidence that each SNP is correctly called is at least 95%.
8 . The method of claim 6 , wherein the confidence that each SNP is correctly called is at least 99%.
9 . The method of claim 1 , wherein the genetic data obtained is noisy and comprises allele drop out errors.
10 . The method of claim 1 , wherein the genetic data obtained is noisy and comprises measurement bias.
11 . The method of claim 1 , wherein the genetic data obtained is noisy and comprises incorrect measurements.
12 . The method of claim 1 , further comprising normalizing the genetic data for differences in amplification and/or measurement efficiency between the loci.