[ABSTRACT]
Somatic mutations can reveal cell lineages during development, health, ageing and disease; however, the rare nature of such mutations makes identifying them time and resource consuming. Short Tandem Repeats (STRs) are highly mutable genomic elements composed of repetitive short motifs, widely distributed within the human’s genome and as such, they are the most promising source for genomic variance among the cells of an individual. Earlier we presented a single-cell mutation discovery platform utilizing chip-based multiplex PCR targeting thousands of STRs. Here we present a significant improvement over the platform that combines efficient synthesis of duplex Molecular Inversion Probes (MIPs), high throughput targeting sequencing technologies together with tailored analysis and adaptive error correction all within an integrated bioinformatics Database Management System (DBMS). By applying this platform to various types of human cells, we demonstrated efficient acquisition of tens-of-thousands targets in single-cell whole-genome amplified DNA and discovered lineage relations among these cells.