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How does next-generation sequencing differ from Sanger sequencing?

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Diagram of a DNA double helix showing its twisted ladder structure, with a close-up of the sugar-phosphate backbone, paired nitrogenous bases (adenine, thymine, cytosine, guanine), and labeled nucleotides and hydrogen bonds. — human genome The human genome is made up of approximately three billion base pairs of deoxyribonucleic acid (DNA). The bases of DNA are adenine (A), thymine (T), guanine (G), and cytosine (C).

Next-generation sequencing (NGS) differs from first-generation Sanger sequencing primarily in its scale, speed, and cost-efficiency. While Sanger sequencing—developed in the 1970s—relies on the enzymatic synthesis of DNA chains that are terminated at specific nucleotides and separated by size, it is a relatively low-throughput process.12

In contrast, next-generation sequencing is characterized by massively parallel production. Key differences include:31

Throughput: NGS allows for the simultaneous sequencing of millions of DNA fragments at once, whereas Sanger sequencing typically processes far fewer sequences per run.12
Efficiency: NGS is significantly faster and more cost-effective than first-generation technologies, enabling the routine whole genome sequencing of organisms, including humans.31
Data Analysis: The high-throughput nature of NGS generates massive datasets in the gigabase range, necessitating advanced bioinformatics for data storage, assembly, and manipulation.12

While Sanger sequencing was foundational for early projects like the Human Genome Project, NGS has largely supplanted it for large-scale genomic analysis.312