Liquid Biopsy Enters 3.0 Era: How Gene Big Data Is Driving Clinical and Multi-Domain Innovation

In mid-July, the bustling Suzhou Industrial Park once again hosted a major event—the 7th Annual Conference on Big Data in Genomics (BDCG-7). Guided by the National Center for Biopharmaceutical Technology Innovation and co-organized by Gene+ Research Institute and Suzhou BioBAY, the conference brought together more than 300 experts and representatives from diverse fields, including oncology, infectious diseases, pathology, laboratory medicine, new drug development, complex diseases, and health management. Together, they contributed their expertise and insights to advance precision medicine in the era of multi-omics.

The conference theme is clear from the outset—“Exploring New ‘Liquid’ States in Omics Applications”—encompassing key terms that best represent the advancement of precision medicine, such as multi-omics, big data, liquid biopsy, and NGS applications, while also providing a platform for exchange and collaboration to explore new technologies, applications, and values.

In recent years, NGS technologies, represented by liquid biopsy, have also become a highly innovative frontier in the field of genetic research. With continuous breakthroughs in omics technologies, the application scope of liquid biopsy continues to expand, demonstrating immense potential across multiple fields including oncology, infectious diseases, and complex disorders. As Dr. Yi Xin, CEO of Gene+, stated at the conference: “Liquid biopsy 1.0 is applied in the oncology field, with landmark applications being ctDNA detection and MRD detection; version 2.0 is applied in the pathogen field, utilizing mNGS, tNGS, and other technologies; while the current version 3.0 represents a breakthrough in the field of complex diseases.

Technological Iteration and Updates,How vast is the potential envisioned by the industry for Liquid Biopsy 3.0? How can real-world data-based genomic big data feed back into clinical practice and scientific research? How do new technologies facilitate precision diagnosis and treatment, thereby realizing the dream of “Medicine for All”?This annual conference, grounded in genomic big data, focuses on the latest research advances and application cases of liquid biopsy in oncology, infectious diseases, complex disorders, and health management. It aims to integrate these fragmented knowledge points and insights, empowering us to usher in a new era characterized by systematic, personalized, and precision approaches.

As an emerging non-invasive testing modality, liquid biopsy is characterized by its non-invasiveness, high safety profile, and repeatability. It can comprehensively reflect the overall mutational landscape of tumors to a certain extent, provide timely and comprehensive assessments of disease progression, and enable real-time monitoring. These advantages have broadened its application scope and expanded the eligible patient population. In 2015, liquid biopsy was named one of the “Top 10 Breakthrough Technologies of the Year” by MIT Technology Review, maintaining its momentum thereafter. In 2017, it was included in the World Economic Forum’s “Top 10 Emerging Technologies of 2017.”

The first major theme of the annual conference was “New Applications of Liquid Biopsy Technology.” Professor Chen Xiang from Xiangya School of Medicine, Central South University; Professor Zhou Qing from Guangdong Provincial People’s Hospital; Professor Ma Fei from the Cancer Hospital, Chinese Academy of Medical Sciences; and Professor Kang Mei from West China Hospital, Sichuan University, shared recent research advances in liquid biopsy technology for skin diseases, lung cancer, breast cancer, and bloodstream infections.

Professor Chen Xiang approached the topic from clinical perspectives, emphasizing that addressing skin diseases requires interdisciplinary integration based on big data, and that basic research into disease mechanisms should be extended to clinical translation. Professor Zhou Qing elaborated on the advances and development of minimal residual disease (MRD) detection technologies in lung cancer, highlighting the importance of MRD detection techniques and strategic selection. Professor Ma Fei addressed whole-course MRD monitoring in breast cancer, stating that the time has matured for MRD detection technology to guide clinical practice. Breakthroughs have been achieved in using test results to inform treatment strategies for high-risk breast cancer subtypes, further improving survival rates among breast cancer patients. In the field of oncology, liquid biopsy has evolved from detecting drug resistance in advanced-stage tumors to assessing MRD in resectable tumors, demonstrating prognostic value that surpasses traditional TNM staging.

One of the breakout sessions at the Annual Conference on Genomic Big Data, “Redefining tNGS for Pathogen Diagnosis,” focused on technological applications in infectious disease scenarios. Experts including Professor Chen Chuanxi from the First Affiliated Hospital of Sun Yat-sen University, Professor Xu Jie from the Ninth People’s Hospital affiliated with Shanghai Jiao Tong University School of Medicine, Professor Lu Binghuai from China-Japan Friendship Hospital, and Dr. Yang Zhenyu from Gene+ engaged in in-depth discussions on topics such as diagnostic and therapeutic needs for ICU bloodstream infections, challenges in diagnosing and treating infections in immunocompromised patients, tNGS as a pathogen detection technology that balances breadth, depth, and accuracy, and its clinical implementation within hospitals.

In clinical practice, the diagnosis of bloodstream infections (BSIs) remains a significant challenge. Traditional diagnostic methods rely on blood culture, which is the simplest, most accurate, and commonly used technique, serving as the microbiological foundation for confirming BSIs. However, its low positivity rate and prolonged turnaround time can adversely impact subsequent clinical treatment decisions. At this conference, Professor Kang Mei from West China Hospital of Sichuan University pointed out that current culture-independent molecular techniques, such as PCR, metagenomic next-generation sequencing (mNGS), and targeted next-generation sequencing (tNGS), can generate reports within 24 hours, significantly improving the timeliness of test results. Furthermore, tNGS technology based on hybrid capture holds promise as a superior diagnostic tool well-suited for infection surveillance.

The 3.0 Era of Liquid Biopsy Advances Toward the Diagnosis of Complex DiseasesComplex diseases, including metabolic disorders, neurodegenerative diseases, and autoimmune conditions, pose significant challenges for both diagnosis and treatment. As Dr. Chen Rongrong, Chief Medical Officer at Gene+, noted, the application of liquid biopsy in complex diseases remains in an exploratory stage, requiring collaborative efforts from research institutes, hospitals, and innovative companies.

At the “Complex Disease Research” sub-forum of the Annual Conference on Genetic Big Data, this issue was explored. Dr. Yanan Cao from Ruijin Hospital, Shanghai Jiao Tong University School of Medicine; Professor Jinchen Li from Xiangya Hospital, Central South University; Professor Guoliang Chai from Xuanwu Hospital, Capital Medical University; Professor Jie Hu from the Institute of Biophysics, Chinese Academy of Sciences; Professor Deming Gou from Shenzhen University; and Dr. Jing Bai from Gene+ engaged in in-depth discussions on topics including the China Metabolic Analytics Project (ChinaMAP), tools for interpreting genetic variants and their applications in autism and Parkinson’s disease, research on neuroimmune diseases, multi-omics technologies for detecting epigenetic mutations, and the application of high-sensitivity plasma cfRNA library preparation and sequencing technology in the clinical diagnosis and classification of pulmonary hypertension.

From oncology to infectious diseases and even complex disorders, the scope of liquid biopsy applications continues to expand. This growth is driven not only by continuous breakthroughs in omics technologies but also by the support provided by genomic big data technology. Genomic big data enables researchers to vertically broaden application areas, such as extending from hematologic malignancies to solid tumors, while also pioneering new frontiers, including ongoing explorations into complex diseases. These advancements provide more powerful scientific tools for understanding, diagnosing, and treating complex diseases.

The second major theme of the Annual Conference on Genetic Big Data was “Clinical Implementation of NGS Testing in Hospitals.” Professor Shi Leming from the School of Life Sciences at Fudan University, Professor Ji Yuan from Zhongshan Hospital Affiliated to Fudan University, and Professor Su Dan from Zhejiang Cancer Hospital shared insights into local implementation practices and research on how genetic big data empowers clinical care.

Professor Shi Leming introduced the latest progress of the HRD standardization project, which was jointly initiated by the National Cancer Center, the National Institutes for Food and Drug Control (NIFDC), and Fudan University, with in-depth participation from Gene+. The project aims to address issues such as the lack of standardized HRD detection methods, SNP site selection, and HRD score thresholds. Currently, the project has achieved phased results and will be further explored in clinical samples.

Professor Ji Yuan shared insights on genetic testing projects from the perspective of the new Laboratory Developed Tests (LDT) regulations. As an LDT pilot institution, Zhongshan Hospital Fudan University has established a working group led by the hospital president and relevant departments to comprehensively evaluate the in-hospital implementation of LDTs, thereby ensuring the quality of LDT reagents and the standard of clinical services. She pointed out that, in addition to policy, technology, and application considerations, healthcare institutions need to join forces with innovative biotechnology companies to accelerate the research, development, production, and use of LDT products, thus meeting urgent clinical needs.

Professor Su cited the practical experience of the Department of Pathology at Zhejiang Cancer Hospital in the application of Laboratory Developed Tests (LDTs), pointing out that the LDT model is a viable pathway for meeting the needs of Minimal Residual Disease (MRD) testing. She emphasized that hospitals must lay a solid foundation in laboratory system construction and the training of LDT-related personnel. Meanwhile, performance verification has been carried out for the Gene+ 1021+ MRD product as part of the hospital’s internal LDT program. She stressed the importance of leveraging the advantages of detection methods while fully understanding their limitations in practice, with a commitment to achieving better and more standardized MRD testing.

How to Accelerate the In-Hospital Implementation of New Technologies? Beyond ensuring sufficient reliability and efficacy, it is essential to align with regulatory policies and establish standardized protocols. The new Laboratory Developed Tests (LDT) policy has opened a new pathway for the rapid in-hospital adoption of novel technologies, concurrently raising standardization challenges. These include issues related to test accessibility, practical operational procedures, training of qualified personnel, and data analysis and interpretation.

The in-hospital implementation of new technologies not only enables faster public access to their benefits but also empowers precision medicine research. According to Dr. Chen Rongrong, Chief Medical Officer at Gene+, over the past year or so, Gene+ has collaborated with major hospitals and experts to achieve multiple outcomes in oncology, pathogenic infections, and complex diseases based on genomic big data. She stated, ““With the hospital-based implementation of Gene+’s 1021+ MRD assay and the initiation of multiple series of studies, MRD is assisting clinicians in devising more precise treatment plans for cancer patients. Biopsy technology has also achieved product translation in infectious diseases. Meanwhile, tNGS has surpassed previous capabilities in breadth, depth, and accuracy, ranging from pathogen identification and typing to drug resistance analysis, thereby enabling faster and better clinical service.”

The Era of Liquid Biopsy 3.0 Is Advancing Vigorously Toward Broader and Deeper Applications, Requiring Close Collaboration Among Research Institutes, Hospitals, and Biotech Innovation Enterprises, with the Latter Playing an Even More Critical Role.

In 2017, Gene+ established its Genomics Research Institute and built a comprehensive system for oncology applied research and product development, leveraging technological platforms such as liquid biopsy, immunohistochemistry, single-cell analysis, and methylation. This system covers areas including clinical oncology, early health screening, pathogenic infection, organ transplantation and injury, and new drug development, and is currently expanding into the research of complex diseases.

To date, Gene+ has engaged in scientific research collaborations and clinical application studies with numerous medical institutions and research institutes both domestically and internationally. The company has undertaken over 700 collaborative projects, led or co-led 13 major special research programs, published more than 320 SCI-indexed papers in prestigious international academic journals such as Nature, Nature Medicine, Nature Communications, and Journal of Thoracic Oncology, with a cumulative impact factor exceeding 3,000. Additionally, Gene+ has been granted over 70 patents and registered more than 80 software copyrights.

As one of the earliest biotechnology innovators to implement MRD in clinical applications, Gene+ is also at the forefront in oncology, infectious diseases, and complex disorders.

In oncology, Gene+ has launched a fully upgraded 1021+ personalized custom MRD assay. The detection region has been expanded by approximately 50% to 2.3 Mb, with sequencing depth increased by 100%. Validated across more than 570,000 samples, the assay employs core probes plus personalized probes developed for lung, colorectal, breast, and pan-cancer applications, achieving an ultra-high depth of 100,000X. Powered by its proprietary ER-Seq technology, the assay enables effective multi-layer noise reduction. This newly upgraded 1021 personalized custom MRD assay is now available for clinical implementation within hospitals, covering initial MRD testing, prognostic prediction, recurrence monitoring, and treatment efficacy assessment.

In the realm of pathogen infection, Gene+ unveiled its new pathogen detection product, tNGS-Max, at the annual conference. This solution provides comprehensive coverage for bloodstream infections, respiratory tract infections, and central nervous system infectious syndromes. Utilizing species- and genus-level probes, it closely approximates the performance of mNGS, meeting 99% of pathogen detection needs. Its high-density tiled probe design achieves a limit of detection (LOD) as low as 5–25 copies/mL, enabling efficient detection of low-pathogen loads. Furthermore, through an integrated design of whole-genome probes for resistance genes combined with high-depth sequencing coverage, it can precisely identify drug-resistance loci.

Even in the more advanced and complex disease domains, Gene+ has initiated the construction of a baseline database for blood cfDNA methylation from Chinese health cohorts, as well as cell-specific methylation maps for the Chinese population. It has established baselines for 40 cell types and, leveraging its proprietary methylation technology, has collaborated with multiple institutions to explore research projects on organ injury. In this regard, Gene+ is truly a “Gene+ Pioneer” in translating scientific exploration into clinical applications.

Even more encouraging is our observation that many products and business models, traditionally confined to circles such as clinical practice, pathology, laboratory testing, and pharmaceutical companies, are increasingly expanding toward consumer-facing markets. For instance, MRD (Minimal Residual Disease) technology, previously accessible only in clinical diagnosis and treatment settings, is gradually becoming part of everyday life for the general public. At the conference, Gene+ officially launched the “Affordable Healing, Healthy Living: Five-Year Care and Public-Benefit Co-Creation” project, designed for postoperative cancer patients. Jointly initiated by Gene+ in collaboration with platforms including JD Health, Volcano Engine, Lighthouse Oncologists, Dongdong Oncology, and Patient Home, this project aims to provide early-stage postoperative patients with highly precise, ultra-affordable, and personalized postoperative rehabilitation plans centered on MRD testing (baseline plus serial monitoring), thereby improving patients’ quality of life and health outcomes.