De novo whole genome sequencing (WGS) is a combination of sequencing and computational techniques that generate complete genomes, which involves taking small fragments of DNA sequences, whether long or short, and then piecing them together without any prior knowledge of the correct order.

The process comprises several stages, such as sequence selection, error-correction, contig assembly, and scaffolding, using various algorithms and software tools. These steps work in tandem to deliver a contiguous genome assembly that can shed light on the genetic diversity, genome structure, and evolution of organisms. Whole-genome assembly using de novo sequencing is akin to solving a giant jigsaw puzzle comprising millions of pieces, where many fragmented sequences are assembled by finding shared reads up to the chromosome level.