A cell-free DNA metagenomic sequencing assay that integrates the host injury response to infection.

Abstract:

:High-throughput metagenomic sequencing offers an unbiased approach to identify pathogens in clinical samples. Conventional metagenomic sequencing, however, does not integrate information about the host, which is often critical to distinguish infection from infectious disease, and to assess the severity of disease. Here, we explore the utility of high-throughput sequencing of cell-free DNA (cfDNA) after bisulfite conversion to map the tissue and cell types of origin of host-derived cfDNA, and to profile the bacterial and viral metagenome. We applied this assay to 51 urinary cfDNA isolates collected from a cohort of kidney transplant recipients with and without bacterial and viral infection of the urinary tract. We find that the cell and tissue types of origin of urinary cfDNA can be derived from its genome-wide profile of methylation marks, and strongly depend on infection status. We find evidence of kidney and bladder tissue damage due to viral and bacterial infection, respectively, and of the recruitment of neutrophils to the urinary tract during infection. Through direct comparison to conventional metagenomic sequencing as well as clinical tests of infection, we find this assay accurately captures the bacterial and viral composition of the sample. The assay presented here is straightforward to implement, offers a systems view into bacterial and viral infections of the urinary tract, and can find future use as a tool for the differential diagnosis of infection.

authors

Cheng AP,Burnham P,Lee JR,Cheng MP,Suthanthiran M,Dadhania D,De Vlaminck I

doi

10.1073/pnas.1906320116

subject

Has Abstract

pub_date

2019-09-10 00:00:00

pages

18738-18744

issue

37

eissn

0027-8424

issn

1091-6490

pii

1906320116

journal_volume

116

pub_type

杂志文章
  • Co-occupancy by multiple cardiac transcription factors identifies transcriptional enhancers active in heart.

    abstract::Identification of genomic regions that control tissue-specific gene expression is currently problematic. ChIP and high-throughput sequencing (ChIP-seq) of enhancer-associated proteins such as p300 identifies some but not all enhancers active in a tissue. Here we show that co-occupancy of a chromatin region by multiple...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1016959108

    authors: He A,Kong SW,Ma Q,Pu WT

    更新日期:2011-04-05 00:00:00

  • IL-15 is a component of the inflammatory milieu in the tumor microenvironment promoting antitumor responses.

    abstract::Previous studies have provided evidence that IL-15 expression within human tumors is crucial for optimal antitumor responses; however, the regulation of IL-15 within the tumor microenvironment (TME) is unclear. We report herein, in analyses of mice implanted with various tumor cell lines, soluble IL-15/IL-15Rα complex...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1814642116

    authors: Santana Carrero RM,Beceren-Braun F,Rivas SC,Hegde SM,Gangadharan A,Plote D,Pham G,Anthony SM,Schluns KS

    更新日期:2019-01-08 00:00:00

  • Purification and characterization of a ubiquitin carrier protein kinase from HeLa cells.

    abstract::Protein ubiquitination plays an important role in ATP-dependent protein turnover, and it also may regulate other cellular events. Covalent attachment of ubiquitin to other proteins is catalyzed by three different enzymes, E1, E2, and E3. We have previously shown that protein ubiquitination can be regulated by phosphor...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.91.24.11601

    authors: Kong SK,Chock PB

    更新日期:1994-11-22 00:00:00

  • Glutamate antagonists limit tumor growth.

    abstract::Neuronal progenitors and tumor cells possess propensity to proliferate and to migrate. Glutamate regulates proliferation and migration of neurons during development, but it is not known whether it influences proliferation and migration of tumor cells. We demonstrate that glutamate antagonists inhibit proliferation of ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.091113598

    authors: Rzeski W,Turski L,Ikonomidou C

    更新日期:2001-05-22 00:00:00

  • Hypersensitivity of Ku80-deficient cell lines and mice to DNA damage: the effects of ionizing radiation on growth, survival, and development.

    abstract::We recently have shown that mice deficient for the 86-kDa component (Ku80) of the DNA-dependent protein kinase exhibit growth retardation and a profound deficiency in V(D)J (variable, diversity, and joining) recombination. These defects may be related to abnormalities in DNA metabolism that arise from the inability of...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.94.25.13588

    authors: Nussenzweig A,Sokol K,Burgman P,Li L,Li GC

    更新日期:1997-12-09 00:00:00

  • Kras mutant genetically engineered mouse models of human cancers are genomically heterogeneous.

    abstract::KRAS mutant tumors are largely recalcitrant to targeted therapies. Genetically engineered mouse models (GEMMs) of Kras mutant cancer recapitulate critical aspects of this disease and are widely used for preclinical validation of targets and therapies. Through comprehensive profiling of exomes and matched transcriptome...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1708391114

    authors: Chung WJ,Daemen A,Cheng JH,Long JE,Cooper JE,Wang BE,Tran C,Singh M,Gnad F,Modrusan Z,Foreman O,Junttila MR

    更新日期:2017-12-19 00:00:00

  • Development of potent gastrin-releasing peptide antagonists having a D-Pro-psi(CH2NH)-Phe-NH2 C terminus.

    abstract::Gastrin-releasing peptide (GRP) is a 27-amino acid neuroendocrine hormone that may play a role in the pathophysiology of small cell lung carcinoma. GRP and bombesin, a structurally related peptide, stimulate the growth of some cultured cell types. C-terminal GRP peptide analogs were developed that inhibited 6 nM bombe...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.90.5.1922

    authors: Leban JJ,Kull FC Jr,Landavazo A,Stockstill B,McDermed JD

    更新日期:1993-03-01 00:00:00

  • Kinetics of mature T-cell development in the thymus.

    abstract::We have reexamined the balance between cell birth, cell maturation, and cell death in the thymus by labeling dividing thymocytes and their progeny in vivo with [3H]-thymidine, isolating clearly defined subpopulations by fluorescence-activated cell sorting, and determining the distribution of label by autoradiography. ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.87.7.2579

    authors: Egerton M,Scollay R,Shortman K

    更新日期:1990-04-01 00:00:00

  • Thermodynamics of aqueous sodium chloride to 823 K and 1 kilobar (100 MPa).

    abstract::It is shown that a very simple semiempirical equation represents quite accurately the thermodynamic properties of aqueous sodium chloride from 373 to 823 K. The equation comprises one Margules term and a Debye-Hückel term. Just the one Margules parameter is freely adjustable because the Debye-Hückel parameter is deter...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.80.24.7689

    authors: Pitzer KS,Li YG

    更新日期:1983-12-01 00:00:00

  • Bax degradation by the ubiquitin/proteasome-dependent pathway: involvement in tumor survival and progression.

    abstract::Previously we reported that proteasome inhibitors were able to overcome Bcl-2-mediated protection from apoptosis. Here we show that inhibition of the proteasome activity in Bcl-2-overexpressing cells accumulates the proapoptotic Bax protein to mitochondria/cytoplasm, where it interacts to Bcl-2 protein. This event was...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.070047997

    authors: Li B,Dou QP

    更新日期:2000-04-11 00:00:00

  • Revealing the structure of a catalytic combustion active-site ensemble combining uniform nanocrystal catalysts and theory insights.

    abstract::Supported metal catalysts are extensively used in industrial and environmental applications. To improve their performance, it is crucial to identify the most active sites. This identification is, however, made challenging by the presence of a large number of potential surface structures that complicate such an assignm...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.2002342117

    authors: Yang AC,Choksi T,Streibel V,Aljama H,Wrasman CJ,Roling LT,Goodman ED,Thomas D,Bare SR,Sánchez-Carrera RS,Schäfer A,Li Y,Abild-Pedersen F,Cargnello M

    更新日期:2020-06-30 00:00:00

  • (2'-5')Oligoadenylate in rat liver: modulation after partial hepatectomy.

    abstract::(2'-5')Oligoadenylate synthetase [(2'-5')A synthetase], which synthesizes a series of oligoadenylates ppp-(A2'p)n5'A [collectively referred to as (2'-5')A], has been described previously in rat liver cells, where its concentration varied with the growth status of this organ--i.e., it decreased during the early phase o...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.80.15.4609

    authors: Etienne-Smekens M,Vandenbussche P,Content J,Dumont JE

    更新日期:1983-08-01 00:00:00

  • Interleukin 12 and B7-1 costimulatory molecule expressed by an adenovirus vector act synergistically to facilitate tumor regression.

    abstract::Stimulation of antitumor immune mechanisms is the primary goal of cancer immunotherapy, and accumulating evidence suggests that effective alteration of the host-tumor relationship involves immunomodulating cytokines and also the presence of costimulatory molecules. To examine the antitumor effect of direct in vivo gen...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.94.20.10889

    authors: Pützer BM,Hitt M,Muller WJ,Emtage P,Gauldie J,Graham FL

    更新日期:1997-09-30 00:00:00

  • Stabilization of electron spin resonance probes for photosynthesis studies.

    abstract::The major obstacle to the study of functional/structural interrelationships of spinach chloroplasts by using spin labels has been the rapid loss of the electron paramagnetic resonance (EPR) signals upon illumination with visible light. The present study demonstrates that the addition of ferredoxin and NADP+ in the pre...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.72.8.3107

    authors: Sun AS,Calvin M

    更新日期:1975-08-01 00:00:00

  • Restoring GABAergic inhibition rescues memory deficits in a Huntington's disease mouse model.

    abstract::Huntington's disease (HD) is classically characterized as a movement disorder, however cognitive impairments precede the motor symptoms by ∼15 y. Based on proteomic and bioinformatic data linking the Huntingtin protein (Htt) and KCC2, which is required for hyperpolarizing GABAergic inhibition, and the important role o...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1716871115

    authors: Dargaei Z,Bang JY,Mahadevan V,Khademullah CS,Bedard S,Parfitt GM,Kim JC,Woodin MA

    更新日期:2018-02-13 00:00:00

  • Chromosome 14 transfer and functional studies identify a candidate tumor suppressor gene, mirror image polydactyly 1, in nasopharyngeal carcinoma.

    abstract::Chromosome 14 allelic loss is common in nasopharyngeal carcinoma (NPC) and may reflect essential tumor suppressor gene loss in tumorigenesis. An intact chromosome 14 was transferred to an NPC cell line using a microcell-mediated chromosome transfer approach. Microcell hybrids (MCHs) containing intact exogenously trans...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0900198106

    authors: Cheung AK,Lung HL,Ko JM,Cheng Y,Stanbridge EJ,Zabarovsky ER,Nicholls JM,Chua D,Tsao SW,Guan XY,Lung ML

    更新日期:2009-08-25 00:00:00

  • Force measurements on cargoes in living cells reveal collective dynamics of microtubule motors.

    abstract::Many cellular cargoes move bidirectionally along microtubules, driven by teams of plus- and minus-end-directed motor proteins. To probe the forces exerted on cargoes during intracellular transport, we examined latex beads phagocytosed into living mammalian macrophages. These latex bead compartments (LBCs) are encased ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1215462109

    authors: Hendricks AG,Holzbaur EL,Goldman YE

    更新日期:2012-11-06 00:00:00

  • The evolution of N-glycan-dependent endoplasmic reticulum quality control factors for glycoprotein folding and degradation.

    abstract::Asn-linked glycans (N-glycans) play important roles in the quality control (QC) of glycoprotein folding in the endoplasmic reticulum (ER) lumen and in ER-associated degradation (ERAD) of proteins by cytosolic proteasomes. A UDP-Glc:glycoprotein glucosyltransferase glucosylates N-glycans of misfolded proteins, which ar...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0704862104

    authors: Banerjee S,Vishwanath P,Cui J,Kelleher DJ,Gilmore R,Robbins PW,Samuelson J

    更新日期:2007-07-10 00:00:00

  • Interactions among Hageman factor, plasma prekallikrein, high molecular weight kininogen, and plasma thromboplastin antecedent.

    abstract::To investigate the earliest steps of the intrinsic clotting pathway, Hageman factor (Factor XII) was exposed to Sephadex gels to which ellagic acid had been adsorbed; Hageman factor was then separated from the gels and studied in the fluid phase. Sephadex-ellagic acid-exposed Hageman factor, whether purified or in pla...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.76.2.958

    authors: Ratnoff OD,Saito H

    更新日期:1979-02-01 00:00:00

  • Drosophila TFIIE: purification, cloning, and functional reconstitution.

    abstract::We present a physical and molecular genetic characterization of Drosophila melanogaster TFIIE (dTFIIE), a component of the basal RNA polymerase II transcription apparatus. We have purified dTFIIE to near homogeneity from nuclear extracts of Drosophila embryos and found that it is composed of two subunits with apparent...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.94.2.433

    authors: Wang X,Hansen SK,Ratts R,Zhou S,Snook AJ,Zehring W

    更新日期:1997-01-21 00:00:00

  • Structural basis for receptor specificity of influenza B virus hemagglutinin.

    abstract::Receptor-binding specificity of HA, the major surface glycoprotein of influenza virus, primarily determines the host ranges that the virus can infect. Influenza type B virus almost exclusively infects humans and contributes to the annual "flu" sickness. Here we report the structures of influenza B virus HA in complex ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0708363104

    authors: Wang Q,Tian X,Chen X,Ma J

    更新日期:2007-10-23 00:00:00

  • Aberrant AKT activation drives well-differentiated liposarcoma.

    abstract::Well-differentiated liposarcoma (WDLPS), one of the most common human sarcomas, is poorly responsive to radiation and chemotherapy, and the lack of animal models suitable for experimental analysis has seriously impeded functional investigation of its pathobiology and development of effective targeted therapies. Here, ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1106127108

    authors: Gutierrez A,Snyder EL,Marino-Enriquez A,Zhang YX,Sioletic S,Kozakewich E,Grebliunaite R,Ou WB,Sicinska E,Raut CP,Demetri GD,Perez-Atayde AR,Wagner AJ,Fletcher JA,Fletcher CD,Look AT

    更新日期:2011-09-27 00:00:00

  • Distinct histone modifications in stem cell lines and tissue lineages from the early mouse embryo.

    abstract::A unique property of the mammalian embryo is that stem cells can be derived from its early tissue lineages. These lineages will give rise to the fetus as well as essential extraembryonic tissues. Understanding how chromatin regulation participates in establishment of these lineages in the embryo and their derived stem...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0914507107

    authors: Rugg-Gunn PJ,Cox BJ,Ralston A,Rossant J

    更新日期:2010-06-15 00:00:00

  • Electrophoretic resolution of three major insulin receptor structures with unique subunit stoichiometries.

    abstract::Plasma membrane insulin receptors, affinity labeled by covalent crosslinking to receptor-bound 125I-labeled insulin, are shown to appear as a heterogeneous population of three major disulfide-linked complexes (Mr 350,000, 320,000, and 290,000) upon electrophoresis in highly porous dodecyl sulfate/polyacrylamide gels i...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.77.12.7137

    authors: Massague J,Pilch PF,Czech MP

    更新日期:1980-12-01 00:00:00

  • Rapid polyether cleavage via extracellular one-electron oxidation by a brown-rot basidiomycete.

    abstract::Fungi that cause brown rot of wood are essential biomass recyclers and also the principal agents of decay in wooden structures, but the extracellular mechanisms by which they degrade lignocellulose remain unknown. To test the hypothesis that brown-rot fungi use extracellular free radical oxidants as biodegradative too...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.95.18.10373

    authors: Kerem Z,Bao W,Hammel KE

    更新日期:1998-09-01 00:00:00

  • Sequences near the termini are required for transposition of the maize transposon Ac in transgenic tobacco plants.

    abstract::Deletion derivatives of the maize transposable element Activator (Ac) were constructed in vitro and inserted into a kanamycin resistance gene. These constructions were then introduced into tobacco protoplasts derived from plants previously transformed with Ac. The ability of each deletion derivative to excise was meas...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.86.23.9385

    authors: Coupland G,Plum C,Chatterjee S,Post A,Starlinger P

    更新日期:1989-12-01 00:00:00

  • Vesicle capture, not delivery, scales up neuropeptide storage in neuroendocrine terminals.

    abstract::Neurons vary in their capacity to produce, store, and release neuropeptides packaged in dense-core vesicles (DCVs). Specifically, neurons used for cotransmission have terminals that contain few DCVs and many small synaptic vesicles, whereas neuroendocrine neuron terminals contain many DCVs. Although the mechanistic ba...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1322170111

    authors: Bulgari D,Zhou C,Hewes RS,Deitcher DL,Levitan ES

    更新日期:2014-03-04 00:00:00

  • Emergence of a bacterial clone with enhanced virulence by acquisition of a phage encoding a secreted phospholipase A2.

    abstract::The molecular basis of pathogen clone emergence is relatively poorly understood. Acquisition of a bacteriophage encoding a previously unknown secreted phospholipase A(2) (designated SlaA) has been implicated in the rapid emergence in the mid-1980s of a new hypervirulent clone of serotype M3 group A Streptococcus. Alth...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0607669103

    authors: Sitkiewicz I,Nagiec MJ,Sumby P,Butler SD,Cywes-Bentley C,Musser JM

    更新日期:2006-10-24 00:00:00

  • Biosynthesis of vitamin B12: structure of precorrin-6x octamethyl ester.

    abstract::13C-labeled precorrin-6x is biosynthesized by cell-free protein preparations from Pseudomonas denitrificans in separate experiments using delta-amino[5-13C]levulinic acid and the corresponding delta-amino[4-13C]- and delta-amino[3-13C]levulinic acid-labeled forms in conjunction with S-[methyl-13C]adenosylmethionine fo...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.87.22.8800

    authors: Thibaut D,Blanche F,Debussche L,Leeper FJ,Battersby AR

    更新日期:1990-11-01 00:00:00

  • Investigation of the validity of species status of Ixodes dammini (Acari: Ixodidae) using rDNA.

    abstract::The two internal transcribed spacers (ITS1 and ITS2) of rDNA of three members of the Ixodes ricinus "complex" (Acari: Ixodidae) were sequenced. Sequence variation was assessed for the North American species I. scapularis, I. dammini, and I. pacificus at three levels: within individual/population, between individuals o...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.90.21.10221

    authors: Wesson DM,McLain DK,Oliver JH,Piesman J,Collins FH

    更新日期:1993-11-01 00:00:00