Detection and prediction of infectious disease

A method of preparing a biological fluid sample from a host for a fragmentomics analysis, the method comprising:

• (a) denaturing a nucleic acid in the biological fluid sample to produce a denatured nucleic acid in the biological fluid sample;
• (b) adding an adapter to the biological fluid sample, wherein the denatured nucleic acid in the biological fluid sample comprises a plurality of microbial cell-free nucleic acid fragments, and wherein the adapter comprises a nucleic acid residue overhang;
• (c) attaching the adapter to a microbial cell-free nucleic acid fragment of the plurality of microbial cell-free nucleic acid fragments while the plurality of microbial cell-free nucleic acid fragments are in the biological fluid sample from the host, to produce an adapted nucleic acid, wherein the microbial cell-free nucleic acid fragment is not extracted from the biological fluid sample before the attaching the adapter;
• (d) annealing a primer to the adapted nucleic acid to produce an annealed primer;
• (e) extending the annealed primer with a polymerase to produce an extended nucleic acid;
• (f) sequencing at least the extended nucleic acid to produce a plurality of microbial cell-free nucleic acid sequence reads;
• and
• (g) analyzing the plurality of microbial cell-free nucleic acid sequence reads for a fragment length characteristic selected from the group consisting of:
• a shape of a distribution, a segment amplitude, a peak shape, a fragment count ratio for two or more segments, a height of helical phasing peaks, a fragment count ratio at two different fragment lengths, a ratio of fragment counts within two different fragment length ranges, a fragment length range within a segment, a ratio of maximum amplitudes for two or more segments, and a fragment length distribution within a subset of reads.