Abstract: Disclosed are methods for evaluating genetic models that are predictive of autoimmune disease phenotype or status. The methods comprise obtaining genotype data from bone marrow transplant recipients and donors. The autoimmune disease phenotype of the transplant recipient after the transplantation may be used evaluate the effect of genotype on the autoimmune disease. Phenotype comparisons may be made to the transplant donor and/or the transplant recipient prior to the transplantation. The methods may be used to validate genetic models associated with autoimmune disease. The genetic models may be based on one or more genetic variants associated with susceptibility to or protection from an autoimmune disease.

Abstract: Disclosed are methods for evaluating genetic models that are predictive of autoimmune disease phenotype or status. The methods comprise obtaining genotype data from bone marrow transplant recipients and donors. The autoimmune disease phenotype of the transplant recipient after the transplantation may be used evaluate the effect of genotype on the autoimmune disease. Phenotype comparisons may be made to the transplant donor and/or the transplant recipient prior to the transplantation. The methods may be used to validate genetic models associated with autoimmune disease. The genetic models may be based on one or more genetic variants associated with susceptibility to or protection from an autoimmune disease.

Abstract: Provided are methods of treating a viral infection, the methods comprising administering, to a subject infected with a virus, a genetic modifying agent that targets one or more regions of the viral genome that are maximally different from the host genome. Also provided are methods comprising administering, to a subject infected with a virus, a genetic modifying agent that targets one or more genes of host cells that harbor the virus, where the targeted gene(s) are necessary to the correct function and replication of the virus but are dispensable to the host cells. Also provided are methods comprising decreasing, in one or more cells in the subject, the amount of susceptibility genetic variant(s); and/or increasing, in one or more cells in the subject, the amount of one or more protective genetic variant(s). Also provided are methods of identifying viral genes associated with survival of a virus.

Abstract: Disclosed herein are systems and methods for evaluating segments of DNA within a single strand or chromosome using matched filtering. DNA within a cell of interest, such as a gamete or embryonic cell, may be imaged at high resolution to provide an input signal. Matched filters may be created for reference signals from reference samples of cells having homologous chromosomes that share the same haplotypes as the DNA within the cell of interest. By applying a matched filter for a given haplotype to the input signal it can be determined whether the DNA within the cell of interest shares the same haplotype as the reference sample. The nucleotide sequence of one or more segments of DNA from the cell of interest may be reconstructed by identifying the haplotypes present in the DNA.

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.

Abstract: Provided are methods for outputting a non-Mendelian risk score, comprising: receiving from a first dataset (i) genotype data for a subject and (ii) genotype data and phenotype data for one or more blood relatives of a subject having a gene of interest; receiving from a second dataset genotype population data and phenotype population data, wherein the population comprises two or more blood relatives; training a model on the first and second datasets to determine a genetic risk in the subject associated with one or more non-Mendelian gene of interest; and outputting a phenotypic risk score for the subject. Also provided are systems and non-transitory machine-readable media for outputting a polygenic risk score for a subject.

Abstract: Provided are methods treating a subject having an autoimmune disorder comprising, for instance, decreasing, in one or more cells in the subject, the amount of one or more genetic variants associated with susceptibility to the autoimmune disorder; and/or increasing, in one or more cells in the subject, the amount of one or more genetic variants protective against the autoimmune disorder. Also provided are methods for decreasing, in the subject, the number of cells that have one or more genetic variants associated with susceptibility to the autoimmune disorder; and/or increasing, in the subject, the number of cells that have one or more genetic variants protective against the autoimmune disorder. Also provided are compositions and isolated cells for use in accordance with the methods.