Provided herein are methods and systems for identifying chimeric nucleic acid fragments, e.g., organism-pathogen chimeric nucleic acid fragments and chromosomal rearrangement chimeric nucleic acid fragments. Also provided herein are methods and systems relating to determining a pathogen integration profile or a chromosomal rearrangement in a biological sample and determining a classification of pathology based at least in part on a pathogen integration profile or a chromosomal rearrangement in a biological sample. In certain aspects of the present disclosure, cell-free nucleic acid molecules from a biological sample are analyzed.