Abstract: Some embodiments relate to techniques for enriching eukaryotic DNA in a DNA sample containing eukaryotic DNA and prokaryotic DNA. A DNA sample comprising eukaryotic DNA and prokaryotic DNA can be accessed. The DNA sample can be treated with one or more restriction enzymes, where at least one of the one or more restriction enzymes is a methylation-specific restriction enzyme that selectively digests prokaryotic DNA by targeting methylation patterns characteristic of prokaryotic genomes, the methylation patterns being absent or rare in eukaryotic DNA. The treated DNA sample can be sequenced.