Abstract: Disclosed herein are methods of using non-error-propagating phasing techniques in combination with sequencing data obtained through more conventional error-propagating approaches to improve phasing of a genome and correct allele balance signals, which may allow for improved determinations of ploidy status of chromosomal segments. Further disclosed herein are methods of using allele balance and depth of read in combination to make improved ploidy status determinations. The techniques described herein may be used in a minimally invasive manner to make ploidy status determinations for an embryo or fetus and to identify chromosomal instability in tumor DNA.

Abstract: Provided are methods for determining a disease risk associated with an embryo that comprise constructing the genome of the embryo based on (i) one or more genetic variants in the embryo, (ii) a paternal haplotype, (iii) a maternal haplotype (iv) a transmission probability of the paternal haplotype, and (v) a transmission probability of the maternal haplotype; assigning a polygenic risk score to the embryo based on the constructed genome of the embryo; determining the disease risk associated with the embryo based on the polygenic risk score; and determining transmission of disease causing genetic variants and/or haplotypes from the paternal genome and/or maternal genome to the embryo. Also provided are methods of determining a range of disease risk for potential children for a mother and a potential sperm donor. Also provided are methods of determining disease risk in an individual.

Abstract: Provided are methods of determining the pathogenicity of a genetic variant, the method comprising: selecting a gene of interest; identifying a network of genes or gene variants that are up-regulated, down-regulated, or co-expressed with the gene of interest, and/or that interact directly or indirectly with the gene of interest; and determining the pathogenicity of the gene of interest based on the presence, absence, and/or expression levels of the network of genes. Also provided are methods of constructing a pathogenicity classifier for a genetic variant, the method comprising training a pathogenicity classifier.