HiFi Genome Sequencing Advances Reproductive Genetics

PacBio, announced the publication of a preprint describing the first major study from the HiFi Solves Sub-fertility Consortium in Asia Pacific. The study highlights how HiFi whole genome sequencing could give researchers a more complete view of reproductive genetics in one workflow, while enabling institutions across Asia-Pacific to analyze data through a shared, federated framework.

Subfertility affects approximately 1 in 6 couples globally, yet genetic evaluation often remains fragmented, requiring multiple sequential tests that can take months or years and still leave couples without a clear genetic explanation. For many couples, genetic testing is not a single answer-seeking moment in time. It is a sequence of separate investigations, each looking at only part of the genome. HiFi sequencing offers a more comprehensive approach by assessing multiple variant types in one workflow, which may help reduce repeat testing, shorten the path to insight, and support more informed reproductive counseling.

In this multicenter study, researchers recruited 96 individuals (47 couples and 2 individual participants) across five leading institutions in Singapore, South Korea, Thailand, and Taiwan. The study focused on couples with unexplained subfertility (>= 1 year) or recurrent pregnancy loss after standard clinical evaluations had ruled out known causes.

Of these, 84 individuals underwent PacBio HiFi whole genome sequencing, enabling comprehensive analysis of multiple forms of genomic variation in a single assay. HiFi sequencing enabled improved resolution of complex and repetitive genomic regions that are difficult to assess using conventional approaches, while also allowing characterization of variants across both partners, reflecting the shared genetic contribution to subfertility. To support collaboration across countries and institutions, the consortium used DNAstack’s federated analysis framework to harmonize analysis while keeping data securely managed by participating sites.

“Subfertility and recurrent pregnancy loss often involve heterogeneous and complex genetic factors that are not fully captured by conventional testing approaches,” said Dr. Saumya Jamuar, corresponding senior author of the study. “Through the HiFi Solves Subfertility Consortium in Asia-Pacific, we were able to bring together multiple leading centers to apply a standardized long-read sequencing approach across diverse patient populations. This collaborative framework enables us to generate robust, comparable datasets at scale, which is critical for understanding the genetic architecture of these conditions. By using HiFi long-read genome sequencing, we can assess multiple variant types in a single test, which may help reduce the need for sequential investigations and, as more evidence is generated, could support evaluation of this approach as a first-line genomic test in subfertility.”

Even in a highly selected cohort where standard evaluations had already ruled out known causes, HiFi sequencing identified clinically relevant genomic findings in approximately one in 10 couples. Likely diagnostic genetic findings were identified in 4.8% of individuals, while additional variants of uncertain significance may inform future research.

“PacBio HiFi long-read sequencing provides a powerful and reliable approach for resolving complex reproductive genetic cases that remain unexplained using conventional testing,” said Professor Ming Chen, Professor and Laboratory Director at Changhua Christian Hospital Medical Center, Taiwan. “This study highlights the importance of collaborative, multi-center efforts in advancing reproductive genomics and improving our understanding of subfertility and recurrent pregnancy loss.”

“This is exactly why HiFi Solves exists,” said Christian Henry, President and Chief Executive Officer of PacBio. “When leading institutions contribute data, expertise and infrastructure, the field can move faster. This study shows how a single, comprehensive HiFi sequencing workflow can help researchers generate stronger evidence for complex reproductive genetics.”

The HiFi Solves Sub-fertility Consortium in Asia Pacific was launched at PRISM Asia 2024 to advance long-read sequencing in reproductive genomics. Its first major findings will now be presented at PRISM 2026 in Fukuoka, Japan, showing the consortium’s progress from formation to multi-center evidence generation.

Next, the consortium plans to expand recruitment across additional Asia-Pacific centers, evaluate broader multi-omic approaches, and explore scalable sequencing workflows that could improve accessibility and cost-efficiency for future reproductive genomics studies. As PacBio advances scalable workflows such as SPRQ-Nx, the consortium expects to evaluate approaches that could support more accessible, cost-efficient reproductive genomics research at larger scale.

This study builds on the broader, global HiFi Solves Consortium, which aims to accelerate discovery, empower researchers, and improve outcomes in rare and genetically complex diseases through global collaboration.

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