- Cancer Genomics and Diagnostics
- Single-cell and spatial transcriptomics
- Renal Transplantation Outcomes and Treatments
- Molecular Biology Techniques and Applications
- Genomics and Phylogenetic Studies
- Prenatal Screening and Diagnostics
- Antimicrobial Resistance in Staphylococcus
- Bacterial Identification and Susceptibility Testing
- Epigenetics and DNA Methylation
- Kawasaki Disease and Coronary Complications
- Hematopoietic Stem Cell Transplantation
- Infective Endocarditis Diagnosis and Management
- Pancreatic and Hepatic Oncology Research
- Gut microbiota and health
- Antibiotic Use and Resistance
- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Antibiotics Pharmacokinetics and Efficacy
- Cytomegalovirus and herpesvirus research
- Antibiotic Resistance in Bacteria
- Clostridium difficile and Clostridium perfringens research
- RNA and protein synthesis mechanisms
- Ocular Infections and Treatments
- Genomics and Rare Diseases
- Genetic factors in colorectal cancer
New York Genome Center
2021-2025
Cornell University
2018-2025
Centre Hospitalier de l’Université de Montréal
2025
École de Technologie Supérieure
2025
Weill Cornell Medicine
2021-2022
Polytechnique Montréal
2016-2022
Wayne State University
2019-2020
Presbyterian Hospital
2019-2020
New York Hospital Queens
2019-2020
NewYork–Presbyterian Hospital
2019-2020
High-throughput metagenomic sequencing offers an unbiased approach to identify pathogens in clinical samples. Conventional sequencing, however, does not integrate information about the host, which is often critical distinguish infection from infectious disease, and assess severity of disease. Here, we explore utility high-throughput cell-free DNA (cfDNA) after bisulfite conversion map tissue cell types origin host-derived cfDNA, profile bacterial viral metagenome. We applied this assay 51...
Chitosan is a family of glucosamine and N-acetyl polysaccharides with poorly understood immune modulating properties. Here, functional U937 macrophage responses were analyzed in response to novel library twenty chitosans controlled degree deacetylation (DDA, 60-98%), molecular weight (1 >100 kDa), acetylation pattern (block vs. random). Specific chitosan preparations (10 or 190 kDa 80% block DDA 3, 5, 10 98% DDA) either induced macrophages release CXCL10 IL-1ra at 5-50 μg/mL, activated the...
Significance Hematopoietic cell transplantation is the gold standard treatment for many blood disorders, including cancers. Nonetheless, frequent post-transplant complications limit long-term benefit of HCT. Here, we find that circulating cell-free DNA a highly versatile analyte monitoring most important HCT: Graft-Versus-Host Disease, infection, graft failure and disease relapse. We show these different therapeutic can be informed from single sequencing assay followed by disease-specific...
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 viruses, creating opportunities for the diagnosis infection via metagenomic sequencing. The total biomass microbial-derived clinical isolates low, which makes sequencing susceptible to contamination alignment noise. Results Here, we report low background correction (LBBC), bioinformatics noise filtering tool informed by...
Differential host responses in coronavirus disease 2019 (COVID-19) and multisystem inflammatory syndrome children (MIS-C) remain poorly characterized. Here, we use next-generation sequencing to longitudinally analyze blood samples from pediatric patients with COVID-19 or MIS-C across three hospitals. Profiling of plasma cell-free nucleic acids uncovers distinct signatures cell injury death between MIS-C, increased multiorgan involvement encompassing diverse types, including endothelial...
Abstract Metagenomic DNA sequencing is a powerful tool to characterize microbial communities but sensitive environmental contamination, in particular when applied samples with low biomass. Here, we present Sample-Intrinsic Found by Tagging and (SIFT-seq) metagenomic assay that robust against contamination introduced during sample preparation. The core idea of SIFT-seq tag the prior isolation library preparation label can be recorded sequencing. Any contaminating after tagging then...
ABSTRACT In solid tumor oncology, circulating DNA (ctDNA) is poised to transform care through accurate assessment of minimal residual disease (MRD) and therapeutic response monitoring. To overcome the sparsity ctDNA fragments in low fraction (TF) settings increase MRD sensitivity, we previously leveraged genome-wide mutational integration plasma whole genome sequencing (WGS). We now introduce MRD-EDGE, a composite machine learning-guided WGS single nucleotide variant (SNV) copy number (CNV)...
Bloodstream infections with Staphylococcus aureus are clinically significant and often treated empirical methicillin resistance (MRSA, methicillin-resistant S. aureus) coverage. However, vancomycin has associated harms. We hypothesized that MRSA screening correlated in bacteremia could help determine the requirement for therapy. reviewed consecutive bacteremias over a 5-year period at two tertiary care hospitals. colonization was evaluated three ways: as tested within 30 days of (30-day...
Abstract Urine is a rich source of nucleic acid biomarkers including cell-free DNA (cfDNA) and RNA for monitoring the health kidney allografts. In this study, we aimed to evaluate whether urine filtration can serve as an alternative commonly used method centrifugation collect urinary fluid cell pellets isolating cfDNA cellular messenger (mRNA). We collected specimens from allograft recipients obtained supernatant pellet each specimen using both paired analyses. performed sequencing...
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 COVID-19, using genome-wide methylation profiling circulating cell-free DNA in plasma. We assessed utility this identify subjects severe two independent, longitudinal cohorts hospitalized patients. Cell-free was performed on 104 plasma samples from 33 patients compared other...
Metagenomic sequencing of microbial cell-free DNA (cfDNA) in blood and urine is increasingly used as a tool for unbiased infection screening. The sensitivity metagenomic cfDNA assays determined by the efficiency which assay recovers vs host-specific cfDNA. We hypothesized that choice methods isolation, library preparation, would affect sequencing.
ABSTRACT Circulating cell-free DNA (ccfDNA) sequencing for low-burden cancer monitoring is limited by sparsity of circulating tumor (ctDNA), the abundance genomic material within a plasma sample, and pre-analytical error rates due to library preparation, errors. Sequencing costs have historically favored development deep targeted approaches overcoming in ctDNA detection, but these techniques are ccfDNA samples, which imposes ceiling on maximal depth coverage panels. Whole genome (WGS) an...
Bloodstream infections with Staphylococcus aureus are clinically significant and often treated empirical methicillin resistance (MRSA, methicillin-resistant S. aureus) coverage. However, vancomycin has associated harms. We hypothesized that MRSA screening correlated in bacteremia could help determine the requirement for therapy. reviewed consecutive bacteremias over a 5-year period at two tertiary care hospitals. colonization was evaluated three ways: as tested within 30 days of (30-day...
Abstract Several approaches for the detection of circulating tumor DNA (ctDNA) are anchored in accurate identification cancer-specific single nucleotide variants (SNVs) plasma. Such limited ultra-low fraction (TF) contexts, such as early cancer or postoperative minimal residual disease, where ctDNA SNVs difficult to distinguish against background sequencing error. these critical low TF contexts is further by sparse amount cell free (cfDNA) plasma (Zviran et al., 2020). To reduce...
Abstract Individual bulk tumor biopsies are invasive and may fail to capture clonal heterogeneity within primary tumors metastatic sites of disease. Further, analyses subclonal variants often hindered by background error rates related tissue preservation methods (e.g. FFPE) sequencing artifact. Use plasma-only ultrasensitive liquid biopsy approaches allow for noninvasive inference clonality dynamically track changes in burden. We previously developed MRD-EDGE, a tumor-informed machine...
Abstract Allogeneic hematopoietic cell transplantation (HCT) provides effective treatment for hematologic malignancies and immune disorders. Monitoring of post-transplant complications is critical, yet current diagnostic options are limited. Here, we show that cell-free DNA (cfDNA) in blood a highly versatile analyte monitoring the most important occur after HCT: graft-versus-host disease (GVHD), frequent complication HCT; infection; relapse underlying disease; graft failure. We demonstrate...
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 viruses, creating opportunities for the diagnosis infection via metagenomic sequencing. The total biomass microbial-derived clinical isolates low, which makes sequencing susceptible to contamination alignment noise. Results: Here, we report Low Biomass Background Correction (LBBC), bioinformatics noise filtering tool...
Conventional culture can be insensitive for the detection of rare infections and common in setting recent antibiotic usage. Patients receiving peritoneal dialysis (PD) with suspected peritonitis have a significant proportion negative conventional cultures. This study examines utility metagenomic sequencing effluent cell-free DNA (cfDNA) evaluating PD patients without peritonitis.Prospective cohort study.We prospectively characterized cfDNA 68 samples obtained from 33 at single center...
Withdrawal Statement The authors have withdrawn their manuscript owing to data from patients who had not been consented being inadvertently used in the preprint. This has corrected version of study published Cell Reports Medicine. Therefore, do wish this work be cited as reference for project. If you any questions, please contact corresponding author.