Comparative analysis of whole genome amplification kits for single-cell genome analysis

Whole genome amplification (WGA) enables detailed analysis of genomic heterogeneity at the cellular level. Here, we systematically compare two commercially available WGA technologies on single cells; Multiple Displacement Amplification in the Qiagen REPLI-g kit (MDA/REPLI-g) and Primary Template-directed Amplification in the BioSkryb ResolveDNA kit (PTA/ResolveDNA). Beyond quality control and genomic profiling, we assessed a cost-effective array-based approach as a complement to low-pass sequencing. Consistent with available benchmarks, PTA/ResolveDNA sequencing libraries consistently outperformed MDA/REPLI-g across quality metrics, including genome coverage breadth and uniformity. CNV calls from PTA-cells showed higher accuracy and sensitivity, including reliable detection of small CNVs at low sequencing depth. SNP array-based analysis corroborated sequencing-based findings, and additionally provided allelic information. Notably, CNV detection from SNP arrays matched the performance of low-pass sequencing, supporting its utility as an cost-effective approach for WGA quality control and single-cell CNV profiling.