Techniques for cancer detection using nucleic acid fragmentation site contexts

A system for determining whether a subject has cancer by analyzing fragmentation in a cell-free deoxyribonucleic acid (cfDNA) sample obtained from the subject, the system comprising:

• at least one computer hardware processor;
• and
• at least one non-transitory computer-readable storage medium storing instructions that, when executed by the at least one computer hardware processor, cause the at least one computer hardware processor to perform:
• accessing sequencing data, the sequencing data previously obtained from sequencing the cfDNA sample, the sequencing data comprising a plurality of reads of cfDNA fragments;
• aligning the plurality of reads to a reference;
• identifying, using results of aligning the plurality of reads to the reference, fragmentation sites of the cfDNA sample and nucleotide subsequences of the reference corresponding to the fragmentation sites;
• determining fragmentation site contexts of the cfDNA sample using the nucleotide subsequences of the reference corresponding to the fragmentation sites;
• generating, using the plurality of fragmentation site contexts, a data structure encoding information about a distribution of fragmentation site contexts of the cfDNA sample;
• and
• determining whether the subject has cancer using the data structure encoding information about the distribution of fragmentation site contexts of the cfDNA sample.

A non-transitory computer-readable storage medium storing instructions that, when executed by at least one computer hardware processor, cause the at least one computer hardware processor to perform a method for determining whether a subject has cancer by analyzing fragmentation in a cell-free deoxyribonucleic acid (cfDNA) sample obtained from the subject, the method comprising:

• accessing sequencing data, the sequencing data previously obtained from sequencing the cfDNA sample, the sequencing data comprising a plurality of reads of cfDNA fragments;
• aligning the plurality of reads to a reference;
• identifying, using results of aligning the plurality of reads to the reference, fragmentation sites of the cfDNA sample and nucleotide subsequences of the reference corresponding to the fragmentation sites;
• determining fragmentation site contexts of the cfDNA sample using the nucleotide subsequences of the reference corresponding to the fragmentation sites;
• generating, using the plurality of fragmentation site contexts, a data structure encoding information about a distribution of fragmentation site contexts of the cfDNA sample;
• and
• determining whether the subject has cancer using the data structure encoding information about the distribution of fragmentation site contexts of the cfDNA sample.