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Article ; Online: Biopsy-free screening for glioma.

Cheng, Alexandre Pellan / Burnham, Philip / De Vlaminck, Iwijn

2018 Volume 10, Issue 12

MeSH term(s)	Biopsy ; Cell-Free Nucleic Acids ; DNA Fragmentation ; Glioma ; Humans
Chemical Substances	Cell-Free Nucleic Acids
Language	English
Publishing date	2018-10-25
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	2467145-9
ISSN	1757-4684 ; 1757-4676
ISSN (online)	1757-4684
ISSN	1757-4676
DOI	10.15252/emmm.201809484
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Cell-free DNA profiling informs all major complications of hematopoietic cell transplantation.

Cheng, Alexandre Pellan / Cheng, Matthew Pellan / Loy, Conor James / Lenz, Joan Sesing / Chen, Kaiwen / Smalling, Sami / Burnham, Philip / Timblin, Kaitlyn Marie / Orejas, José Luis / Silverman, Emily / Polak, Paz / Marty, Francisco M / Ritz, Jerome / De Vlaminck, Iwijn

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

2022 Volume 119, Issue 4

MeSH term(s)	Biomarkers ; Cell-Free Nucleic Acids ; DNA Fingerprinting ; DNA Methylation ; Disease Progression ; Graft vs Host Disease/blood ; Graft vs Host Disease/diagnosis ; Graft vs Host Disease/etiology ; Hematopoietic Stem Cell Transplantation/adverse effects ; Hematopoietic Stem Cell Transplantation/methods ; Humans ; Liquid Biopsy/methods ; Organ Specificity/genetics ; Postoperative Complications/blood ; Postoperative Complications/diagnosis ; Postoperative Complications/etiology ; Recurrence ; Transplantation, Homologous
Chemical Substances	Biomarkers ; Cell-Free Nucleic Acids
Language	English
Publishing date	2022-01-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2113476118
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 1148: Show issues

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Article ; Online: Biopsy‐free screening for glioma

Alexandre Pellan Cheng / Philip Burnham / Iwijn De Vlaminck

EMBO Molecular Medicine, Vol 10, Iss 12, Pp n/a-n/a (2018)

2018

Abstract: Circulating tumor DNA (ctDNA) is a promising diagnostic marker for many cancers and can be noninvasively assayed from blood. For diagnosing glioma, this approach has unfortunately proven to be of limited use since glioma contribute minimal ctDNA to the ... ...

Abstract	Circulating tumor DNA (ctDNA) is a promising diagnostic marker for many cancers and can be noninvasively assayed from blood. For diagnosing glioma, this approach has unfortunately proven to be of limited use since glioma contribute minimal ctDNA to the blood circulation. A more promising avenue may therefore be to hunt for ctDNA in cerebrospinal fluid (CSF). The study by Mouliere et al in this issue of EMBO Molecular Medicine demonstrates that shallow whole‐genome sequencing of CSF‐cfDNA can be used to detect copy number alterations in glioma‐derived ctDNA, providing a low cost strategy to screen for glioma.
Keywords	Medicine (General) ; R5-920 ; Genetics ; QH426-470
Language	English
Publishing date	2018-12-01T00:00:00Z
Publisher	Wiley
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Cell-free DNA tissues of origin by methylation profiling reveals significant cell, tissue, and organ-specific injury related to COVID-19 severity.

Cheng, Alexandre Pellan / Cheng, Matthew Pellan / Gu, Wei / Sesing Lenz, Joan / Hsu, Elaine / Schurr, Erwin / Bourque, Guillaume / Bourgey, Mathieu / Ritz, Jerome / Marty, Francisco M / Chiu, Charles Y / Vinh, Donald C / De Vlaminck, Iwijn

Med (New York, N.Y.)

2021 Volume 2, Issue 4, Page(s) 411–422.e5

Abstract: Background: Coronavirus disease 2019 (COVID-19) primarily affects the lungs, but evidence of systemic disease with multi-organ involvement is emerging. Here, we developed a blood test to broadly quantify cell-, tissue-, and organ-specific injury due to ... ...

Abstract	Background: Coronavirus disease 2019 (COVID-19) primarily affects the lungs, but evidence of systemic disease with multi-organ involvement is emerging. Here, we developed a blood test to broadly quantify cell-, tissue-, and organ-specific injury due to COVID-19. Methods: Our test leverages genome-wide methylation profiling of circulating cell-free DNA in plasma. We assessed the utility of this test to identify subjects with severe disease in two independent, longitudinal cohorts of hospitalized patients. Cell-free DNA profiling was performed on 104 plasma samples from 33 COVID-19 patients and compared to samples from patients with other viral infections and healthy controls. Findings: We found evidence of injury to the lung and liver and involvement of red blood cell progenitors associated with severe COVID-19. The concentration of cell-free DNA correlated with the World Health Organization (WHO) ordinal scale for disease progression and was significantly increased in patients requiring intubation. Conclusions: This study points to the utility of cell-free DNA as an analyte to monitor and study COVID-19. Funding: This work was supported by NIH grants 1DP2AI138242 (to I.D.V.), R01AI146165 (to I.D.V., M.P.C., F.M.M., and J.R.), 1R01AI151059 (to I.D.V.), K08-CA230156 (to W.G.), and R33-AI129455 to C.Y.C., a Synergy award from the Rainin Foundation (to I.D.V.), a SARS-CoV-2 seed grant at Cornell (to I.D.V.), a National Sciences and Engineering Research Council of Canada fellowship PGS-D3 (to A.P.C.), and a Burroughs-Wellcome CAMS Award (to W.G.). D.C.V. is supported by a Fonds de la Recherche en Sante du Quebec Clinical Research Scholar Junior 2 award. C.Y.C. is supported by the California Initiative to Advance Precision Medicine, and the Charles and Helen Schwab Foundation.
MeSH term(s)	COVID-19 ; Cell-Free Nucleic Acids ; Humans ; Methylation ; SARS-CoV-2/genetics ; Virus Diseases
Chemical Substances	Cell-Free Nucleic Acids
Language	English
Publishing date	2021-01-16
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	2666-6340
ISSN (online)	2666-6340
DOI	10.1016/j.medj.2021.01.001
Database	MEDical Literature Analysis and Retrieval System OnLINE

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

Cheng, Alexandre Pellan / Burnham, Philip / Lee, John Richard / Cheng, Matthew Pellan / Suthanthiran, Manikkam / Dadhania, Darshana / De Vlaminck, Iwijn

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

2019 Volume 116, Issue 37, Page(s) 18738–18744

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 ... ...

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.
MeSH term(s)	Bacterial Infections/diagnosis ; Bacterial Infections/microbiology ; Bacterial Infections/urine ; Biomarkers/urine ; Cell-Free Nucleic Acids/genetics ; Cell-Free Nucleic Acids/isolation & purification ; Cell-Free Nucleic Acids/urine ; DNA Methylation/genetics ; DNA, Bacterial/genetics ; DNA, Bacterial/isolation & purification ; DNA, Bacterial/urine ; DNA, Viral/genetics ; DNA, Viral/isolation & purification ; DNA, Viral/urine ; Diagnosis, Differential ; Female ; High-Throughput Nucleotide Sequencing ; Host-Pathogen Interactions/genetics ; Host-Pathogen Interactions/immunology ; Humans ; Kidney/cytology ; Kidney/immunology ; Kidney/microbiology ; Kidney/pathology ; Kidney Failure, Chronic/surgery ; Kidney Transplantation/adverse effects ; Male ; Metagenome/genetics ; Metagenomics/methods ; Neutrophil Infiltration/immunology ; Postoperative Complications/diagnosis ; Postoperative Complications/immunology ; Postoperative Complications/microbiology ; Postoperative Complications/urine ; Transplant Recipients ; Urinary Bladder/cytology ; Urinary Bladder/immunology ; Urinary Bladder/microbiology ; Urinary Bladder/pathology ; Urinary Tract Infections/diagnosis ; Urinary Tract Infections/immunology ; Urinary Tract Infections/microbiology ; Urinary Tract Infections/urine ; Virus Diseases/diagnosis ; Virus Diseases/immunology ; Virus Diseases/urine ; Virus Diseases/virology
Chemical Substances	Biomarkers ; Cell-Free Nucleic Acids ; DNA, Bacterial ; DNA, Viral
Language	English
Publishing date	2019-08-26
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.1906320116
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Cell-Free DNA in Blood Reveals Significant Cell, Tissue and Organ Specific injury and Predicts COVID-19 Severity.

Cheng, Alexandre Pellan / Cheng, Matthew Pellan / Gu, Wei / Lenz, Joan Sesing / Hsu, Elaine / Schurr, Erwin / Bourque, Guillaume / Bourgey, Mathieu / Ritz, Jerome / Marty, Francisco / Chiu, Charles Y / Vinh, Donald Cuong / Vlaminck, Iwijn De

medRxiv : the preprint server for health sciences

2020

Abstract: COVID-19 primarily affects the lungs, but evidence of systemic disease with multi-organ involvement is emerging. Here, we developed a blood test to broadly quantify cell, tissue, and organ specific injury due to COVID-19, using genome-wide methylation ... ...

Abstract	COVID-19 primarily affects the lungs, but evidence of systemic disease with multi-organ involvement is emerging. Here, we developed a blood test to broadly quantify cell, tissue, and organ specific injury due to COVID-19, using genome-wide methylation profiling of circulating cell-free DNA in plasma. We assessed the utility of this test to identify subjects with severe disease in two independent, longitudinal cohorts of hospitalized patients. Cell-free DNA profiling was performed on 104 plasma samples from 33 COVID-19 patients and compared to samples from patients with other viral infections and healthy controls. We found evidence of injury to the lung and liver and involvement of red blood cell progenitors associated with severe COVID-19. The concentration of cfDNA correlated with the WHO ordinal scale for disease progression and was significantly increased in patients requiring intubation. This study points to the utility of cell-free DNA as an analyte to monitor and study COVID-19.
Keywords	covid19
Language	English
Publishing date	2020-07-29
Publishing country	United States
Document type	Preprint
DOI	10.1101/2020.07.27.20163188
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: A metagenomic DNA sequencing assay that is robust against environmental DNA contamination.

Mzava, Omary / Cheng, Alexandre Pellan / Chang, Adrienne / Smalling, Sami / Djomnang Kounatse, Liz-Audrey / Lenz, Joan / Longman, Randy / Steadman, Amy / Salvatore, Mirella / Suthanthiran, Manikkam / Lee, John R / Mason, Christopher E / Dadhania, Darshana / De Vlaminck, Iwijn

bioRxiv : the preprint server for biology

2021

Abstract: Metagenomic DNA sequencing is a powerful tool to characterize microbial communities but is sensitive to environmental DNA contamination, in particular when applied to samples with low microbial biomass. Here, we present contamination-free metagenomic DNA ...

Abstract	Metagenomic DNA sequencing is a powerful tool to characterize microbial communities but is sensitive to environmental DNA contamination, in particular when applied to samples with low microbial biomass. Here, we present contamination-free metagenomic DNA sequencing (Coffee-seq), a metagenomic sequencing assay that is robust against environmental contamination. The core idea of Coffee-seq is to tag the DNA in the sample prior to DNA isolation and library preparation with a label that can be recorded by DNA sequencing. Any contaminating DNA that is introduced in the sample after tagging can then be bioinformatically identified and removed. We applied Coffee-seq to screen for infections from microorganisms with low burden in blood and urine, to identify COVID-19 co-infection, to characterize the urinary microbiome, and to identify microbial DNA signatures of inflammatory bowel disease in blood.
Language	English
Publishing date	2021-11-23
Publishing country	United States
Document type	Preprint
DOI	10.1101/2021.11.22.469599
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: A metagenomic DNA sequencing assay that is robust against environmental DNA contamination.

Mzava, Omary / Cheng, Alexandre Pellan / Chang, Adrienne / Smalling, Sami / Djomnang, Liz-Audrey Kounatse / Lenz, Joan Sesing / Longman, Randy / Steadman, Amy / Gómez-Escobar, Luis G / Schenck, Edward J / Salvatore, Mirella / Satlin, Michael J / Suthanthiran, Manikkam / Lee, John R / Mason, Christopher E / Dadhania, Darshana / De Vlaminck, Iwijn

Nature communications

2022 Volume 13, Issue 1, Page(s) 4197

Abstract	Metagenomic DNA sequencing is a powerful tool to characterize microbial communities but is sensitive to environmental DNA contamination, in particular when applied to samples with low microbial biomass. Here, we present Sample-Intrinsic microbial DNA Found by Tagging and sequencing (SIFT-seq) a metagenomic sequencing assay that is robust against environmental DNA contamination introduced during sample preparation. The core idea of SIFT-seq is to tag the DNA in the sample prior to DNA isolation and library preparation with a label that can be recorded by DNA sequencing. Any contaminating DNA that is introduced in the sample after tagging can then be bioinformatically identified and removed. We applied SIFT-seq to screen for infections from microorganisms with low burden in blood and urine, to identify COVID-19 co-infection, to characterize the urinary microbiome, and to identify microbial DNA signatures of sepsis and inflammatory bowel disease in blood.
MeSH term(s)	COVID-19 ; DNA ; DNA Contamination ; DNA, Bacterial/genetics ; DNA, Environmental ; High-Throughput Nucleotide Sequencing ; Humans ; Metagenomics ; Sequence Analysis, DNA
Chemical Substances	DNA, Bacterial ; DNA, Environmental ; DNA (9007-49-2)
Language	English
Publishing date	2022-07-21
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-022-31654-0
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Cell-Free DNA in Blood Reveals Significant Cell, Tissue and Organ Specific injury and Predicts COVID-19 Severity

Cheng, Alexandre Pellan / Cheng, Matthew Pellan / Gu, Wei / Lenz, Joan Sesing / Hsu, Elaine / Schurr, Erwin / Bourque, Guillaume / Bourgey, Mathieu / Ritz, Jerome / Marty, Francisco M / Chiu, Charles Y / Vinh, Donald Cuong / De Vlaminck, Iwijn

medRxiv

Abstract	COVID-19 primarily affects the lungs, but evidence of systemic disease with multi-organ involvement is emerging. Here, we developed a blood test to broadly quantify cell, tissue, and organ specific injury due to COVID-19, using genome-wide methylation profiling of circulating cell-free DNA in plasma. We assessed the utility of this test to identify subjects with severe disease in two independent, longitudinal cohorts of hospitalized patients. Cell-free DNA profiling was performed on 104 plasma samples from 33 COVID-19 patients and compared to samples from patients with other viral infections and healthy controls. We found evidence of injury to the lung and liver and involvement of red blood cell progenitors associated with severe COVID-19. The concentration of cfDNA correlated with the WHO ordinal scale for disease progression and was significantly increased in patients requiring intubation. This study points to the utility of cell-free DNA as an analyte to monitor and study COVID-19.
Keywords	covid19
Language	English
Publishing date	2020-07-29
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2020.07.27.20163188
Database	COVID19

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Article ; Online: Separating the signal from the noise in metagenomic cell-free DNA sequencing

Philip Burnham / Nardhy Gomez-Lopez / Michael Heyang / Alexandre Pellan Cheng / Joan Sesing Lenz / Darshana M. Dadhania / John Richard Lee / Manikkam Suthanthiran / Roberto Romero / Iwijn De Vlaminck

Microbiome, Vol 8, Iss 1, Pp 1-

2020 Volume 9

Abstract: Abstract Background Cell-free DNA (cfDNA) in blood, urine, and other biofluids provides a unique window into human health. A proportion of cfDNA is derived from bacteria and viruses, creating opportunities for the diagnosis of infection via metagenomic ... ...

Abstract	Abstract Background Cell-free DNA (cfDNA) in blood, urine, and other biofluids provides a unique window into human health. A proportion of cfDNA is derived from bacteria and viruses, creating opportunities for the diagnosis of infection via metagenomic sequencing. The total biomass of microbial-derived cfDNA in clinical isolates is low, which makes metagenomic cfDNA sequencing susceptible to contamination and alignment noise. Results Here, we report low biomass background correction (LBBC), a bioinformatics noise filtering tool informed by the uniformity of the coverage of microbial genomes and the batch variation in the absolute abundance of microbial cfDNA. We demonstrate that LBBC leads to a dramatic reduction in false positive rate while minimally affecting the true positive rate for a cfDNA test to screen for urinary tract infection. We next performed high-throughput sequencing of cfDNA in amniotic fluid collected from term uncomplicated pregnancies or those complicated with clinical chorioamnionitis with and without intra-amniotic infection. Conclusions The data provide unique insight into the properties of fetal and maternal cfDNA in amniotic fluid, demonstrate the utility of cfDNA to screen for intra-amniotic infection, support the view that the amniotic fluid is sterile during normal pregnancy, and reveal cases of intra-amniotic inflammation without infection at term. Video abstract.
Keywords	Cell-free DNA ; Metagenomics ; Biomarkers ; Infectious disease ; Prenatal health ; Microbial ecology ; QR100-130
Language	English
Publishing date	2020-02-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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