This study characterized somatic mutations in chronic traumatic encephalopathy (CTE) and performed whole-genome sequencing of single neurons isolated from prefrontal cortex (PFC) of postmortem human brain of individuals with CTE, repetitive head impacts but without CTE (RHI), or non-disease control, along with bulk whole-genome sequencing performed on each individual as a reference genome for variant calling. Single neuron genomes were amplified using primary template-directed amplification (PTA) or multiplexed end-tagging amplification of complementary strands (META-CS).

Single-neuron amplified genome libraries were sequenced (WGS) on Illumina instruments and aligned to the human reference genome GRCh37. Two sequencing modalities were used, including PTA and META-CS, which is a duplex consensus sequencing method, to perform somatic mutation calling in single neurons with the matched bulk. The single-cell dataset includes a total of 349 single-neuron genome sequences (88 PTA, 261 META-CS). Sequence files are in either .bam (PTA) or .fastq.gz (META-CS) format.