A method of analyzing a biological sample of an organism, the biological sample including a mixture of cell-free DNA molecules from M tissues types, M being an integer greater than two, the method comprising: identifying N genomic sites, wherein N is an integer of at least 10, wherein, for one or more other samples, a first set of the N genomic sites each have a coefficient of variation of methylation levels of at least 0.15 across the M tissue types and each have a difference between a maximum and a minimum methylation level for the M tissue types that exceeds 0.1, the first set including at least 10 of the N genomic sites; for each of the M tissue types: obtaining N tissue-specific methylation levels at the N genomic sites, N being greater than or equal to M, wherein the N tissue-specific methylation levels form a matrix A of dimensions N by M; analyzing a plurality of cell-free DNA molecules from the biological sample, the plurality of cell-free DNA molecules being at least 1,000 cell-free DNA molecules, wherein analyzing a cell-free DNA molecule includes: identifying a location of the cell-free DNA molecule in a reference genome corresponding to the organism; measuring N mixture methylation levels at the N genomic sites using a first group of the plurality of cell-free DNA molecules that are each located at any one of N genomic sites of the reference genome corresponding to the organism, wherein the N mixture methylation levels form a methylation vector b; and solving for a composition vector x that provides the methylation vector b for the matrix A, wherein solving for the composition vector x includes solving Ax=b; and for each of one or more components of the composition vector x: using the component to determine an amount of a corresponding tissue type of the M tissue types in the mixture. identifying N genomic sites, wherein N is an integer of at least 10, wherein, for one or more other samples, a first set of the N genomic sites each have a coefficient of variation of methylation levels of at least 0.15 across the M tissue types and each have a difference between a maximum and a minimum methylation level for the M tissue types that exceeds 0.1, the first set including at least 10 of the N genomic sites; for each of the M tissue types: obtaining N tissue-specific methylation levels at the N genomic sites, N being greater than or equal to M, wherein the N tissue-specific methylation levels form a matrix A of dimensions N by M; analyzing a plurality of cell-free DNA molecules from the biological sample, the plurality of cell-free DNA molecules being at least 1,000 cell-free DNA molecules, wherein analyzing a cell-free DNA molecule includes: identifying a location of the cell-free DNA molecule in a reference genome corresponding to the organism; measuring N mixture methylation levels at the N genomic sites using a first group of the plurality of cell-free DNA molecules that are each located at any one of N genomic sites of the reference genome corresponding to the organism, wherein the N mixture methylation levels form a methylation vector b; and solving for a composition vector x that provides the methylation vector b for the matrix A, wherein solving for the composition vector x includes solving Ax=b; and for each of one or more components of the composition vector x: using the component to determine an amount of a corresponding tissue type of the M tissue types in the mixture. <EOS>