AsianScientist (Jul. 27, 2026) – Decoding the human genome through population genetics has produced valuable insights into human health and evolution. For decades, genotyping microarrays have been the go-to tools in population genetics, enabling landmark studies that have identified thousands of disease-linked variants. Yet, their limitations are increasingly difficult to ignore.
Array designs are based on known variants at the time of manufacture, and tend to be skewed toward populations of European ancestry. This ascertainment bias is a significant challenge in population genetics, especially when studying more diverse or underrepresented populations. It is an issue that initiatives like the Human Pangenome Reference Consortium are working to address, by building a richer, multi-ancestry map that better reflects the full breadth of human genetic diversity.
“Legacy microarrays fundamentally struggle to discover novel or rare variants. Because they were primarily designed using data from populations of European ancestry, they also perform poorly for Asian cohorts,” said Emily M. Leproust, PhD, CEO and co-founder of Twist Bioscience.
A global leader offering next-generation sequencing (NGS) products and services across the biological continuum, Twist Bioscience surpasses legacy array technology with an ecosystem of tools that deliver workflows ideal for population-scale sequencing. Leveraging probe panel design expertise and in-house enzyme engineering, Twist unleashes both scientifically superior and operationally feasible sequencing at scale.
“Twist brings the power of silicon-based DNA synthesis to NGS,” added Dr. Leproust. “We enable researchers to affordably sequence and build robust, representative genomic databases from the ground up, rather than relying on shoehorned legacy tools.”
Streamlining Library Preparation
One of these tools is the Twist FlexPrep™ UHT Library Preparation Kit, which simplifies and optimizes ultra-high-throughput sequencing. Built on Normalization by Ligation™ (NBL) technology powered by Twist’s high conversion efficiency ligase, the FlexPrep Kit removes the need for individual sample quantification and concentration adjustment prior to library preparation. In large-cohort studies, where DNA inputs can vary considerably across samples, that single step traditionally consumes enormous time and resources. With NBL, the chemistry self-normalizes across a wide range of genomic DNA inputs—from 30 to 300 nanograms—allowing researchers to skip upfront quantification entirely and pool samples early in the workflow.
The efficiency gains are substantial. Researchers can process up to 1,152 samples in a single 96-well plate sequencing run, while reducing costly pipette tip consumption by more than 75 percent—from over 17,000 to under 4,000 per plate. What previously required 12 deep-well plates of laborious plate management now resolves to three 384-well plates and a single 96-well plate by end of day.
The FlexPrep Kit’s real-world impact is best illustrated by the experience of US-based genetic testing firm, Gene by Gene, presented at a webinar. Facing growing sample volumes and the shrinking economics of microarrays, the company fully migrated its sample volume to an NGS-based workflow. After integrating the FlexPrep Kit with its sequencing platform, Gene by Gene shut down around 40 incubators and eliminated the hybridization steps that had previously required two full working days. With the same number of personnel, the lab was able to double or triple its processing output. Unlike fixed-probe arrays, the NGS-based workflow also allowed the team to tune sequencing depth by sample, from 0.5x coverage for straightforward ancestry applications to 4x for higher-confidence variant calls.
Genotyping at Scale
With library preparation streamlined, researchers face their next choice: what to sequence. For population genetics studies requiring coverage of hundreds of thousands of known variants across massive cohorts, the Twist Genotyping Panel – Human 600k provides a sequencing-based alternative to standard genotyping arrays.
Comprising 594,275 probes targeting over 600,000 genomic sites, the Twist Human Genotyping Panel covers the most commonly used variants in population screening studies and genome-wide association studies (GWAS). Critically, it achieves this using Twist Bioscience’s double-stranded DNA probe synthesis, which delivers the uniform coverage and low off-target rates that distinguish NGS-based genotyping from array-based methods. The panel is also easily customizable with a custom spike-in panel.
The NGS approach captures context around probe targets, enabling discovery of novel adjacent variants rather than simply confirming what was already known. When paired with the FlexPrep Kit, NGS can overcome barriers related to cost per sample and throughput.
“Researchers get deeper, more reliable data with fewer sequencing reads per sample compared to both arrays and competing NGS panels,” said Dr Leproust. “Biobanks, large-scale cohort researchers, and pharmacogenomics initiatives are finding the Twist Genotyping Panel incredibly valuable. Any community looking to upgrade from legacy array to sequencing data without breaking their budget is adopting it.”
Additionally, for researchers focused on multi-ancestry studies, they can consider the Twist Diversity SNP Panel. The panel has 600,000 probes covering approximately 1.4 million single-nucleotide polymorphisms (SNPs) curated to serve as an ethnicity-neutral genotyping standard, and can be used standalone or spiked into existing exome workflows.
Panels Tailored to Specific Needs
In population genetics, no two studies ask the same question. Whether it is to build representative databases for specific ethnic groups or carry out GWAS focused on disease variants prevalent in particular communities, many studies require content tailored to their unique goals—which Twist Bioscience can support through the customization of its catalog fixed panels.
With Twist Custom NGS Panels, researchers can design panels targeting virtually any genomic region of interest. Twist Bioscience’s proprietary algorithms optimize probe sequences for uniform capture efficiency. The scalability and flexibility of the panels allow them to support probe size as small as 100 to over a million probes per pool.
“A researcher can come to us with a concept or a list of targets, and we can iterate a design and manufacture a production-ready, highly uniform custom panel in a matter of weeks—significantly faster than traditional manufacturing methods,” shared Dr. Leproust.
For researchers whose questions extend beyond genotyping into rare variant discovery, disease gene identification or research-grade exome findings, Twist Exome 2.0 completes the NGS ecosystem. The panel enriches the human exome, approximately 36.5 megabases covering all major protein-coding regions, using probes designed against the latest genome assemblies and incorporating disease-causing variants from databases including ClinVar, ACMG73, GenCode and RefSeq.
In comparative studies conducted by a third-party laboratory, Twist Exome 2.0 achieved fold-80 scores of 1.3 against three competing panels—the uniform coverage of any commercially available exome enrichment product. It also covers 97 percent of target bases at 30x depth with only 6 Gb of sequencing.
For population-scale exome programs where per-sample sequencing costs are closely managed, that efficiency translates directly into larger cohorts and faster answers. In one instance, Twist Bioscience designed a custom spike-in panel as an expansion to Twist Exome 2.0 for the Human Pangenome Reference Consortium.
Complementing the sequencing ecosystem, Twist Bioscience collaborates with leading informatics partners such as SeqOne, an AI-powered NGS bioinformatics platform that provides end-to-end variant analysis.
Toward a Truly Inclusive Genomics
More than half of the world’s population lives in Asia, yet the continent remains underrepresented in the genomic databases that underpin drug development, disease risk prediction and public health policy. Addressing that gap requires both the scientific rigor to generate high-quality data and the operational scalability to generate it at a population level.
“The era of compromising with legacy microarrays is over,” said Dr. Leproust. “Twist Bioscience provides the ultra-high-throughput, cost-effective and highly uniform NGS tools necessary to build truly representative, multi-ethnic population genomics databases at a massive scale.”
From library preparation to genotyping, Twist Bioscience offers a streamlined, highly automated NGS workflow. For biobank initiatives and researchers committed to building a more equitable genomic science, Twist Bioscience’s NGS ecosystem may be exactly what the future of population genetics needs.
For Research Use Only. Not for use in diagnostic procedures.
Reach out to Twist Bioscience to learn more about its population genomics solutions here.
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Source: Twist Bioscience, Shutterstock/Sudarsan Thobias
Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.
