New Library Normalization and Amplification Tools Support Oncology Sequencing

Repetitive and homopolymer-rich regions are particularly prone to insertion–deletion errors, while normalization steps are difficult to automate without introducing bias. A new set of technologies now targets these bottlenecks by combining an advanced library normalization method with an improved amplification system designed to increase accuracy in difficult-to-sequence regions.

Watchmaker Genomics (Boulder, CO, USA) will unveil EquiPlex Normalization Kit and Equinox Prime Library Amplification Master Mix at the European Society of Human Genetics (ESHG) 2026 meeting in Gothenburg, Sweden. The products are designed to address workflow scalability and amplification accuracy, with an emphasis on oncology-focused sequencing where data quality is critical. Both advances reflect an approach centered on protein engineering and integrated workflow design. The company will present the technologies in a featured workshop titled “From Multiomics to Multiplexing: Integrated Advances in DNA, RNA, and Epigenomic Profiling” on Monday, June 15.

EquiPlex repurposes Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9 as a stoichiometric molecular binding tool rather than a cutting enzyme. The method captures a fixed number of molecules from each library regardless of starting concentration, enabling rapid, automated normalization across applications and sample types. By design, it eliminates library concentration quality control (QC), dilution calculations, and variable-volume pipetting that complicate automation and can cause pooling variability and sequencing imbalance. EquiPlex is compatible with established DNA sequencing, RNA sequencing, and methylation workflows without requiring protocol redesign.

Equinox Prime is engineered to reduce polymerase slippage in homopolymer and other repetitive genomic regions prone to indel artifacts. It is described as improving variant-calling accuracy in applications where indel precision is critical, including somatic oncology workflows such as microsatellite instability profiling. Beyond indel performance, the master mix delivers low error rates, high library yields, and uniform guanine–cytosine (GC) coverage. The formulation is intended to support whole genome sequencing (WGS), whole exome sequencing (WES), and additional sequencing applications.

The CRISPR-enabled normalization strategy underpinning EquiPlex is also being adapted as a core component of a novel polymerase chain reaction (PCR)-free WGS solution to streamline fragmentation, normalization, and library construction. The workshop will highlight approaches to improve sequencing quality, simplify workflows, and enable scalability across DNA, RNA, and epigenomic applications, including the debut of both technologies.

“Normalization of libraries prior to pooling has always been an annoyance, especially when working at scale,” said Graham Wiley, PhD, Director of Clinical Genomics Center at Oklahoma Medical Research Foundation. “Our previous pipelines would often still have an amount of variability that left us needing to perform additional sequencing to reach coverage goals. With Equiplex we've finally found the level of pooling consistency we were searching for.”

“Researchers have historically had to make trade-offs in library amplification performance, balancing yield and coverage uniformity against sequencing accuracy depending on the application,” said Brian Kudlow, CSO of Watchmaker. “Equinox Prime was engineered to eliminate those compromises by delivering improved indel accuracy in repetitive regions alongside low error rates, high yields, and even GC coverage in a single solution.”

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