Global Launch of the First Personal Reference Genome Service Project (PRGSP) to Unveil More Secrets of Life

On the evening of March 31, 2018 (Beijing Time), at the 5th NGS Innovation Developers Conference held in Nanjing, GrandOmics Biosciences Co., Ltd. (hereinafter referred to as “GrandOmics”) and GeneKang (Beijing) Technology Co., Ltd. (hereinafter referred to as “GeneKang”) jointly announced the launch of the “Personal Reference Genome Service Project,” beginning to offer a new “Personal Reference Genome” service to the global market.

This service plan will employ the latest sequencing platforms, including ONT GridION/PromethION, Bionano Saphyr, Illumina, and 10X Genomics, as well as high-resolution biochip platforms, to analyze each sample using multiple platforms. Through genome assembly and phasing, a diploid personal reference genome can be obtained. Finally, five types of variants—SNPs, InDels, SVs, STRs, and methylation—will be detected simultaneously.

On this basis, they may become the first to redefine the technical standards for “Whole Genome Sequencing (WGS)” on a global scale, ushering in the era of the “Personal Reference Genome.”

Next-generation sequencing (NGS) is currently the mainstream approach. Whole-genome sequencing (WGS) generally refers to performing 30× coverage NGS on a sample, followed by alignment of the sequencing data to the human reference genome sequence to identify single nucleotide polymorphisms (SNPs) and insertions/deletions (InDels), as well as a subset of copy number variations (CNVs) and short tandem repeats (STRs). This type of testing has become the de facto highest sequencing standard in applications such as NGS-based diagnosis of genetic disorders and preconception carrier screening.

However, we are also well aware that more than 50% of the human genome consists of repetitive sequences. Whole-genome sequencing (WGS) based on next-generation sequencing (NGS) cannot effectively detect genomic variations in repetitive regions.

Furthermore, a critical yet long-overlooked aspect is that human genomic variation encompasses not only single-nucleotide variants (SNVs) but also extensive structural variants (SVs/CNVs), short tandem repeats (STRs), and DNA methylation modifications. Whole-genome sequencing (WGS) based on next-generation sequencing technologies fails to detect a substantial proportion of these variant types, resulting in the so-called “genomic dark matter” phenomenon. This also explains why the positive diagnostic yield of WGS in the field of genetic disease diagnosis remains far below ideal targets.

The “Personal Reference Genome,” highlighted by third-generation sequencing and optical mapping, utilizes ultra-long read data: Oxford Nanopore data are assembled to generate high-completeness contigs; Bionano DLS data are then used for scaffolding; Illumina data are subsequently applied to correct partial errors in the reference genome; finally, 10X Genomics data are integrated for phasing, thereby yielding a high-quality, diploid personal reference genome map.

Based on a personal reference genome, Illumina data were used for SNP and InDel identification, Nanopore data for SV/STR/methylation detection, and Bionano data for SV identification. These variants were further validated using biochip data. By integrating all these data and results, a “Personal Pan-Genomic Variant Set” was generated.

Personal reference genomes will serve as foundational data for newborns in the future, providing a critical comparative resource for early cancer screening. They can also be applied to the diagnosis of complex genetic disorders and preconception carrier screening. Furthermore, certain “individual-specific” sequences within personal reference genomes will play a significant role in advancing our understanding of human evolution and individual traits.

According to the current plan, GrandOmics Biosciences and GeneKang will build a large-scale sequencing and analysis platform, aiming to achieve personal reference genome service capacity for 10,000 samples (Phase I: 10K) within 2–3 years, and for 10 million samples (Phase II: 10M) within 3–10 years. Due to production and R&D costs, the “Personal Reference Genome” service is currently priced at RMB 100,000 per sample in China and USD 20,000 per sample in other countries worldwide. This cutting-edge technical service is now available globally.

From left to right: Hao Xiangwen, Founder of GeneKang; Wang Depeng, CEO of GrandOmics Biosciences; and Cao Han, Founder of Bionano.

GrandOmics Biosciences CEO Wang Depeng defines the company as an enterprise that “does not imitate, does not follow, but strives to create and pioneer the future.” It is a world-leading company specializing in the application of third-generation sequencing technologies for genetic disease and tumor detection.

He stated, “As early as 2016, we had already participated in and completed the first reference-sequence-level Chinese reference genome project, ‘Huaxia No. 1.’ The launch of this ‘Personal Reference Genome Service Program’ aims to leverage updated technologies and more comprehensive protocols to detect and annotate the full spectrum of personal genomic variants, ushering in a new era in the field of genomic medicine.”

“GeneKang specializes in the analysis and interpretation of personal whole-genome data, as well as the development of genetic applications. We continue to invest in building a knowledge base for whole-genome interpretation and developing corresponding technical tools, with the aim of making genetic data an infrastructure for healthy living and improving public health,” said Hao Xiangwen, CEO of GeneKang. “Unveiling the ‘true face’ of individual genomes and interpreting the information they contain aligns perfectly with our original mission through the ‘Personal Reference Genome Service Initiative.’ We believe this project will undoubtedly advance the field of genomics, reveal more of life’s ‘inner workings,’ and ensure that genetic testing technology truly benefits the general public.”