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Whole-genome sequencing (WGS)

A high-resolution view of the entire genome using NGS technology

What is whole-genome sequencing?

Whole-genome sequencing (WGS) is a comprehensive method for analyzing entire genomes. Genomic information has been instrumental in identifying inherited disorders, characterizing the mutations that drive cancer progression, and tracking disease outbreaks. Rapidly dropping sequencing costs and the ability to produce large volumes of data with today’s sequencers make whole-genome sequencing a powerful tool for genomics research.

While this method is commonly associated with sequencing human genomes, the scalable, flexible nature of next-generation sequencing (NGS) technology makes it equally useful for sequencing any species, such as agriculturally important livestock, plants, or disease-related microbes.

Close up, side view of a female scientist interacting with the touch screen monitor on a NovaSeq 6000, selecting from the sequencing screen; green status bar; blurry image in the foreground

Advantages of whole-genome sequencing

  • Provides a high-resolution, base-by-base view of the genome
  • Captures both large and small variants that might be missed with targeted approaches
  • Identifies potential causative variants for further follow-up studies of gene expression and regulation mechanisms
  • Delivers large volumes of data in a short amount of time to support assembly of novel genomes

An uncompromised view of the genome

Unlike focused approaches such as exome sequencing or targeted resequencing, which analyze a limited portion of the genome, whole-genome sequencing delivers a comprehensive view of the entire genome. It is ideal for discovery applications, including identifying causative variants and novel genome assembly.

Whole-genome sequencing can detect single nucleotide variants, insertions/deletions, copy number changes, and large structural variants. Due to recent technological innovations, the latest genome sequencers can perform whole-genome sequencing more efficiently than ever.

Key whole-genome sequencing methods

Large whole-genome sequencing

Sequencing large genomes (> 5 Mb), such as plant, animal, or human genomes, can provide valuable information for disease research and population genetics.

Small whole-genome sequencing

Small genome sequencing (≤ 5 Mb) involves sequencing the entire genome of a bacterium, virus, or other microbe. Without requiring bacterial culture, researchers can sequence thousands of small organisms in parallel using NGS.

De novo sequencing

De novo sequencing refers to sequencing a novel genome where there is no reference sequence available. NGS enables fast, accurate characterization of any species.

Phased sequencing

Phased sequencing, or genome phasing, distinguishes between alleles on homologous chromosomes to resolve their inheritance, resulting in whole-genome haplotypes. This information is often important for genetic disease studies.

Human whole-genome sequencing

Previously a challenging application, human whole-genome sequencing has never been simpler. It offers the most detailed view into our genetic code.

Long-read sequencing

Long reads can help resolve challenging regions of the genome, such as those containing highly variable or highly repetitive elements.

Expanding possibilities in genome sequencing

Learn how Illumina innovations are redefining the limits of what's possible in genome sequencing.
Dr Steve Barnard, Dr Joe Devaney, and Dr Bekim Sadikovic discuss groundbreaking technologies that simplify workflows and expand the frontiers of discovery.

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Featured whole-genome sequencing workflow

This user-friendly three-step WGS workflow provides a fully featured, rapid solution for labs and delivers high-quality insights across the entire genome for all variant classes.

1
Library preparation
2
Sequencing
3
Data analysis

Featured products

Illumina DNA Prep

A fast, integrated workflow for a wide range of applications, from human whole-genome sequencing to amplicons, plasmids, and microbial species.

NovaSeq 6000 Reagent Kit

Reagent kits for the NovaSeq 6000 System provide ready-to-use cartridge-based reagents for cluster generation and SBS.

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Multiomics multiplies your discovery power

See how you can use multiomics to better connect genotype to phenotype and obtain a full cellular readout not found through single omic approaches.

Learn more about multiomics

How scientists use WGS

The time is now for microbiome studies

Whole-genome shotgun sequencing and transcriptomics provide researchers and pharmaceutical companies with data to refine drug discovery and development.

Analyzing leukemia samples with WGS

A New England Journal of Medicine study found that using WGS to assess leukemia samples produced more accurate results, in less time, than karyotyping or fluorescence in situ hybridization.

Featured content

Mapped read technology

Unlock long-distance genomic information, resolve challenging-to-map regions, and simplify your sequencing workflow with proximity mapped read technology.

Whole-genome sequencing FAQ

WGS is a method that is used to gain comprehensive insights by analyzing entire genomes. Advancements in next-generation sequencing coupled with the flexible and scalable nature of NGS technologies make WGS useful for studying genetic material from humans, animals, plants, microbes, and viruses.1
Overview of an NGS workflow:

  1. DNA extraction—Isolate DNA from the sample.
  2. DNA fragmentation—Break DNA into smaller pieces for sequencing.
  3. DNA library preparation—Add adapters and prepare fragments for sequencing.
  4. DNA library sequencing—Run the prepared library on an NGS system.
  5. Data analysis and interpretation—Align reads, assemble the genome, and interpret results.

Whole-genome sequencing plays a critical role in human health. WGS helps researchers understand mutations in tumors that may drive cancer, assess inherited disease risk and carrier status, and gain insights into the genetic makeup of individuals for personalized medicine studies.

In public health, WGS is used to conduct infectious disease research, detect and track disease outbreaks, monitor the spread of infectious diseases, and identify emerging variants. WGS is also used in basic genetics research.1

Watch our WGS webinar and learn about accelerating precision medicine research with low-cost whole-genome sequencing technologies.

Sequencing approaches range from targeted to comprehensive. Targeted sequencing focuses on specific genes or genomic regions, typically selected based on a defined indication. Whole-exome sequencing broadens this scope by assessing multiple variant types across the protein coding regions of the genome. In contrast, whole-genome sequencing provides a comprehensive view of the entire genome, enabling detection of single nucleotide variants (SNVs), insertions and deletions, copy number variations, and large structural variants.

Some limitations of WGS include technical difficulties with data handling and interpretation of certain regions of the genome such as noncoding regions. There are also challenges with the use of some short-read technology for WGS and its ability to resolve long repetitive regions or structural variants.2



While technically a short-read technology, proximity mapped read technology, suitable for WGS needs, generates accurate long-range genomic insights.

The unique workflow maintains the link between the original long DNA template and the resulting short sequencing reads, enabling enhanced detection of structural variants, ultra-long phasing of genetic variants, and improved mapping in low-complexity regions.

Learn more about proximity mapped read technology and our DRAGEN secondary analysis pipeline.

To help you meet your research objectives, we offer a range of user-friendly primary, secondary, tertiary, and cloud-based sequencing data analysis solutions. For additional information, visit our sequencing data analysis resource hub or the DRAGEN secondary analysis pipeline page to find the right solution for your data needs.

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Related methods

Additional resources

Illumina sequencing platforms

Our innovative next-generation sequencing (NGS) platforms deliver exceptional data quality and accuracy at a massive scale. View benchtop and production-scale sequencers and find resources designed to help you choose the right platform.

Sequencing services

Find high-quality whole-genome and other sequencing services that deliver analyzed data to researchers.

Sequencing Method Explorer

Use this interactive tool to explore experimental NGS library preparation methods compiled from the scientific literature.

Speak to a specialist

Talk to an expert to learn more about solutions for whole-genome sequencing.

References

  1. Centers for Disease Control and Prevention (CDC). Whole Genome Sequencing (WGS). CDC PulseNet. https://www.cdc.gov/pulsenet/php/wgs/index.html. Updated February 28, 2024. Accessed November 6, 2025.
  2. Brlek P, Bulić L, Bračić M, et al. Implementing Whole Genome Sequencing (WGS) in Clinical Practice: Advantages, Challenges, and Future Perspectives. Cells. 2024;13(6):504. Published 2024 Mar 13. doi:10.3390/cells13060504