Multicenter expert consensus on application of targeted nanopore pathogen sequencing technology in prevention and treatment of infections in organ transplantation_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

HUANG Yiming ^1,2 , SUN Yunke ³ , WANG Pusen ^1,2 , ZHAO Dong ^1,2 , QUE Weitao ^1,2 , FANG Taishi ^1,2 , CHEN Qijun ^1,2 , YANG Liang ³ , XIA Yu ⁴ , GAO Wei ⁵ , GUO Wenzhi ⁶ , FU Zhiren ⁷ , LI Guangming ⁸ , KONG Lingxiang ⁹ , WANG Shouping ⁹ , CAI Jinzhen ¹⁰ , LÜ Guoyue ¹¹ , WU Zhongjun ¹² , CHEN Gang ¹³ ,  YANG Jiayin ⁹ ,  ZHONG Lin ^1,2,3

1. Department of Liver Surgery and Organ Transplantation Center, Shenzhen Third People’s Hospital, Shenzhen, Guangdong 518112, P. R. China;
2. National Clinical Research Center for Infectious Disease, Shenzhen, Guangdong 518112, P. R. China;
3. School of Medcine, Southern University of Science and Technology, Shenzhen, Guangdong 518055, P. R. China;
4. School of Environment, Southern University of Science and Technology, Shenzhen, Guangdong 518055, P. R. China;
5. Department of Liver Transplantation, Organ Transplantation Center, Tianjin First Central Hospital, Tianjin 300190, P. R. China;
6. Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, P. R. China;
7. Department of General Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, P. R. China;
8. Department of Organ Transplantation, You’an Hospital, Capital Medical University, Beijing 100069, P. R. China;
9. Organ Transplant Center, West China Hospital, Sichuan University, Chengdu 610041, P. R. China;
10. Organ Transplant Center of Affiliated Hospital of Qingdao University, Qingdao, Shandong 266000, P. R. China;
11. Organ Transplant Center of The First Hospital of Jilin University, Changchun 130031, P. R. China;
12. Organ Transplant Center of The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P. R. China;
13. Organ Transplant Center of Tongji Hospital Affiliated to Huazhong University of Science and Technology, Wuhan 430014, P. R. China;

Corresponding author：

YANG Jiayin, Email: doctoryjy@scu.edu.cn; ZHONG Lin, Email: zhonglin1@medmail.com.cn

Keywords：

organ transplantation; targeted nanopore pathogensequencing; third-generation sequencing; postoperative infection; antimicrobial resistance gene prediction

DOI：

10.7507/1007-9424.202501067

Video：

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Organ transplantation is a critical treatment for end-stage organ diseases, yet postoperative infections significantly affect patient outcomes. Traditional diagnostic methods for infections often fall short in meeting the demands of precise prevention and treatment due to limitations in sensitivity, specificity, and speed. Targeted nanopore pathogen sequencing technology, characterized by its long-read capability, real-time detection, and adaptability, has shown unique potential in pathogen identification, structural variation analysis, and antimicrobial resistance gene profiling. This offers new insights into the prevention and management of postoperative infections. This expert consensus focuses on the standardized application of this technology in managing infections following organ transplantation, addressing its principles, clinical recommendations, and diagnostic workflows. By exploring its features and value in infectious disease diagnosis, the expert consensus provides standardized guidance on sample processing and result interpretation. The development of this consensus aims to promote the rational use of nanopore sequencing in diagnosing and treating post-transplant infections, enhance diagnostic accuracy and efficiency, improve patient outcomes, and facilitate the widespread adoption of this technology.

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2.	Gulati G, Song J, Florea AD, et al. Purpose and criteria for blood smear scan, blood smear examination, and blood smear review. Ann Lab Med, 2013, 33(1): 1-7.
3.	Peri AM, Harris PNA, Paterson DL. Culture-independent detection systems for bloodstream infection. Clin Microbiol Infect, 2022, 28(2): 195-201.
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14.	Burguete SR, Maselli DJ, Fernandez JF, et al. Lung transplant infection. Respirology, 2013, 18(1): 22-38.
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16.	Schmaldienst S, Dittrich E, Hörl WH. Urinary tract infections after renal transplantation. Curr Opin Urol, 2002, 12(2): 125-130.
17.	Deamer D, Akeson M, Branton D. Three decades of nanopore sequencing. Nat Biotechnol, 2016, 34(5): 518-524.
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26.	Nurk S, Meleshko D, Korobeynikov A, et al. metaSPAdes: a new versatile metagenomic assembler. Genome Res, 2017, 27(5): 824-834.

1. Cassini A, Högberg LD, Plachouras D, et al. Attributable deaths and disability-adjusted life-years caused by infections with antibiotic-resistant bacteria in the EU and the European Economic Area in 2015: a population-level modelling analysis. Lancet Infect Dis, 2019, 19(1): 56-66.
2. Gulati G, Song J, Florea AD, et al. Purpose and criteria for blood smear scan, blood smear examination, and blood smear review. Ann Lab Med, 2013, 33(1): 1-7.
3. Peri AM, Harris PNA, Paterson DL. Culture-independent detection systems for bloodstream infection. Clin Microbiol Infect, 2022, 28(2): 195-201.
4. Garvey G, Shakarisaz D, Ruiz-Ruiz F, et al. Microretroreflector-sedimentation immunoassays for pathogen detection. Anal Chem, 2014, 86(18): 9029-9035.
5. Jain M, Olsen HE, Paten B, et al. The Oxford Nanopore MinION: delivery of nanopore sequencing to the genomics community. Genome Biol, 2016, 17(1): 239. doi: 10.1186/s13059-016-1103-0.
6. van Dijk EL, Jaszczyszyn Y, Naquin D, et al. The third revolution in sequencing technology. Trends Genet, 2018, 34(9): 666-681.
7. Sun Y, Li X, He J, et al. Rapid diagnosis of Mycoplasma pneumoniae and prediction of antibiotic resistance by nanopore adaptive sampling. iLABMED, 2024, 2(4): 266-276.
8. Cheng H, Sun Y, Yang Q, et al. A rapid bacterial pathogen and antimicrobial resistance diagnosis workflow using Oxford nanopore adaptive sequencing method. Brief Bioinform, 2022, 23(6): bbac453.
9. Larsson DGJ, Flach CF. Antibiotic resistance in the environment. Nat Rev Microbiol, 2022, 20(5): 257-269.
10. Pendleton KM, Erb-Downward JR, Bao Y, et al. Rapid pathogen identification in bacterial pneumonia using real-time metagenomics. Am J Respir Crit Care Med, 2017, 196(12): 1610-1612.
11. Trulock EP. Lung transplantation. Am J Respir Crit Care Med, 1997, 155(3): 789-818.
12. Rose TM. CODEHOP-mediated PCR— a powerful technique for the identification and characterization of viral genomes. Virol J, 2005, 2: 20. doi: 10.1186/1743-422X-2-20.
13. Kritikos A, Manuel O. Bloodstream infections after solid-organ transplantation. Virulence, 2016, 7(3): 329-340.
14. Burguete SR, Maselli DJ, Fernandez JF, et al. Lung transplant infection. Respirology, 2013, 18(1): 22-38.
15. Restrepo A, Clark NM; Infectious Diseases Community of Practice of the American Society of Transplantation. Nocardia infections in solid organ transplantation: Guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation. Clin Transplant, 2019, 33(9): e13509.doi: 10.1111/ctr.13509.
16. Schmaldienst S, Dittrich E, Hörl WH. Urinary tract infections after renal transplantation. Curr Opin Urol, 2002, 12(2): 125-130.
17. Deamer D, Akeson M, Branton D. Three decades of nanopore sequencing. Nat Biotechnol, 2016, 34(5): 518-524.
18. Technologies ON. Input DNA/RNA QC. https://nanoporetech.com/document/input-dna-rna-qc#assessing-input-rna. 2024: 13.
19. De Coster W, D’Hert S, Schultz DT, et al. NanoPack: visualizing and processing long-read sequencing data. Bioinformatics, 2018, 34(15): 2666-2669.
20. De Coster W, Rademakers R. NanoPack2: population-scale evaluation of long-read sequencing data. Bioinformatics, 2023, 39(5): btad311. doi: 10.1093/bioinformatics/btad311.
21. Li H. Minimap2: pairwise alignment for nucleotide sequences. Bioinformatics, 2018, 34(18): 3094-3100.
22. Li H. New strategies to improve minimap2 alignment accuracy. Bioinformatics, 2021, 37(23): 4572-4574.
23. Kim D, Song L, Breitwieser FP, et al. Centrifuge: rapid and sensitive classification of metagenomic sequences. Genome Res, 2016, 26(12): 1721-1729.
24. Wood DE, Lu J, Langmead B. Improved metagenomic analysis with Kraken 2. Genome Biol, 2019, 20(1): 257. doi: 10.1186/s13059-019-1891-0.
25. Wu Z, Che Y, Dang C, et al. Nanopore-based long-read metagenomics uncover the resistome intrusion by antibiotic resistant bacteria from treated wastewater in receiving water body. Water Res, 2022, 226: 119282. doi: 10.1016/j.watres.2022.119282.
26. Nurk S, Meleshko D, Korobeynikov A, et al. metaSPAdes: a new versatile metagenomic assembler. Genome Res, 2017, 27(5): 824-834.

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