title: Diagnosis of Sepsis with Cell-free DNA by Next-Generation Sequencing Technology in ICU Patients.
abstract: Bacteremia is a common serious manifestation of disease in the intensive care unit (ICU), which requires quick and accurate determinations of pathogens to select the appropriate antibiotic treatment. To overcome the shortcomings of traditional bacterial culture (BC), we have adapted next-generation sequencing (NGS) technology to identify pathogens from cell-free plasma DNA.
  
  
  
  In this study, 78 plasma samples from ICU patients were analyzed by both NGS and BC methods and verified by PCR amplification/Sanger sequencing and ten plasma samples from healthy volunteers were analyzed by NGS as negative controls to define or calibrate the threshold of the NGS methodology.
  
  
  
  Overall, 1578 suspected patient samples were found to contain bacteria or fungi by NGS, whereas ten patients were diagnosed by BC. Seven samples were diagnosed with bacterial or fungal infection both by NGS and BC. Among them, two samples were diagnosed with two types of bacteria by NGS, whereas one sample was diagnosed with two types of bacteria by BC, which increased the detectability of bacteria or fungi from 11 with BC to 17 with NGS. Most interestingly, 14 specimens were also diagnosed with viral infection by NGS. The overall diagnostic sensitivity was significantly increased from 12.82% (10/78) by BC alone to 30.77% (24/78) by NGS alone for ICU patients, which provides more useful information for establishing patient treatment plans.
  
  
  
  NGS technology can be applied to detect bacteria in clinical blood samples as an emerging diagnostic tool rich in information to determine the appropriate treatment of septic patients.
authors.affiliation: Department of Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Long
authors.affiliation: Binhai Genomics Institute, Tianjin Translational Genomics Center, BGI-Tianjin, BGI-Shenzhen, Tianjin, China; Shenzhen Key Laboratory of Unknown Pathogen Identification, Shenzhen, China; BGI-Shenzhen, Shenzhen, China.
authors.forename: Yinxin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Binhai Genomics Institute, Tianjin Translational Genomics Center, BGI-Tianjin, BGI-Shenzhen, Tianjin, China; Shenzhen Key Laboratory of Unknown Pathogen Identification, Shenzhen, China; BGI-Shenzhen, Shenzhen, China.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Gong
authors.affiliation: Binhai Genomics Institute, Tianjin Translational Genomics Center, BGI-Tianjin, BGI-Shenzhen, Tianjin, China; Shenzhen Key Laboratory of Unknown Pathogen Identification, Shenzhen, China; BGI-Shenzhen, Shenzhen, China.
authors.forename: Ruixue
authors.initials: R
authors.lastname: Sun
authors.affiliation: Department of Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Longxiang
authors.initials: L
authors.lastname: Su
authors.affiliation: Binhai Genomics Institute, Tianjin Translational Genomics Center, BGI-Tianjin, BGI-Shenzhen, Tianjin, China; Shenzhen Key Laboratory of Unknown Pathogen Identification, Shenzhen, China; BGI-Shenzhen, Shenzhen, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Lin
authors.affiliation: Binhai Genomics Institute, Tianjin Translational Genomics Center, BGI-Tianjin, BGI-Shenzhen, Tianjin, China; Shenzhen Key Laboratory of Unknown Pathogen Identification, Shenzhen, China; BGI-Shenzhen, Shenzhen, China.
authors.forename: Ao
authors.initials: A
authors.lastname: Shen
authors.affiliation: Binhai Genomics Institute, Tianjin Translational Genomics Center, BGI-Tianjin, BGI-Shenzhen, Tianjin, China; Shenzhen Key Laboratory of Unknown Pathogen Identification, Shenzhen, China; BGI-Shenzhen, Shenzhen, China.
authors.forename: Jiali
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Binhai Genomics Institute, Tianjin Translational Genomics Center, BGI-Tianjin, BGI-Shenzhen, Tianjin, China; Shenzhen Key Laboratory of Unknown Pathogen Identification, Shenzhen, China; BGI-Shenzhen, Shenzhen, China.
authors.forename: Zhuoma
authors.initials: Z
authors.lastname: Caiji
authors.affiliation: Binhai Genomics Institute, Tianjin Translational Genomics Center, BGI-Tianjin, BGI-Shenzhen, Tianjin, China; Shenzhen Key Laboratory of Unknown Pathogen Identification, Shenzhen, China; BGI-Shenzhen, Shenzhen, China.
authors.forename: Xinying
authors.initials: X
authors.lastname: Wang
authors.affiliation: Binhai Genomics Institute, Tianjin Translational Genomics Center, BGI-Tianjin, BGI-Shenzhen, Tianjin, China; Shenzhen Key Laboratory of Unknown Pathogen Identification, Shenzhen, China; BGI-Shenzhen, Shenzhen, China.
authors.forename: Dongfang
authors.initials: D
authors.lastname: Li
authors.affiliation: Binhai Genomics Institute, Tianjin Translational Genomics Center, BGI-Tianjin, BGI-Shenzhen, Tianjin, China; Shenzhen Key Laboratory of Unknown Pathogen Identification, Shenzhen, China; BGI-Shenzhen, Shenzhen, China.
authors.forename: Honglong
authors.initials: H
authors.lastname: Wu
authors.affiliation: Binhai Genomics Institute, Tianjin Translational Genomics Center, BGI-Tianjin, BGI-Shenzhen, Tianjin, China; Complete Genomics, Inc., Mountain View, California, USA; Shenzhen Key Laboratory of Unknown Pathogen Identification, Shenzhen, China; BGI-Shenzhen, Shenzhen, China. Electronic address: bgi_tanhongdong@126.com.
authors.forename: Hongdong
authors.initials: H
authors.lastname: Tan
mesh_terms: D016470:Bacteremia / Q000097:blood / Q000175:diagnosis / Q000382:microbiology; D001424:Bacterial Infections / Q000097:blood / Q000175:diagnosis* / Q000382:microbiology; D016022:Case-Control Studies; D004269:DNA, Bacterial / Q000097:blood*; D004271:DNA, Fungal / Q000097:blood; D016469:Fungemia / Q000097:blood / Q000175:diagnosis / Q000382:microbiology; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007362:Intensive Care Units; D009181:Mycoses / Q000097:blood / Q000175:diagnosis / Q000382:microbiology; D018805:Sepsis / Q000097:blood / Q000175:diagnosis* / Q000382:microbiology
chemical_list: D004269:DNA, Bacterial; D004271:DNA, Fungal
keywords: Bacteremia; Blood culture; Next-generation sequencing; Pathogen detection; cfDNA