A5067443364- Cancer Genomics and Diagnostics
- Lung Cancer Treatments and Mutations
- Genetic factors in colorectal cancer
- Molecular Biology Techniques and Applications
- RNA modifications and cancer
- Liver Disease Diagnosis and Treatment
- Genomic variations and chromosomal abnormalities
- Hepatocellular Carcinoma Treatment and Prognosis
- Pancreatic and Hepatic Oncology Research
- Advanced biosensing and bioanalysis techniques
- Genetic Associations and Epidemiology
- Ovarian cancer diagnosis and treatment
- RNA Interference and Gene Delivery
- Genomics and Rare Diseases
- Prenatal Screening and Diagnostics
- Epigenetics and DNA Methylation
- Lung Cancer Research Studies
- Cancer-related molecular mechanisms research
- Cancer Cells and Metastasis
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Cleft Lip and Palate Research
- Gastrointestinal disorders and treatments
- Immunotherapy and Immune Responses
- Lung Cancer Diagnosis and Treatment
- Cytomegalovirus and herpesvirus research
Johns Hopkins University
2016-2025
Johns Hopkins Medicine
2022-2025
Sidney Kimmel Comprehensive Cancer Center
2017-2025
University of Baltimore
2018-2024
Noninvasive liquid biopsy analysis of circulating tumor DNA permits direct detection early-stage cancers.
Abstract Non-invasive approaches for cell-free DNA (cfDNA) assessment provide an opportunity cancer detection and intervention. Here, we use a machine learning model detecting tumor-derived cfDNA through genome-wide analyses of fragmentation in prospective study 365 individuals at risk lung cancer. We validate the using independent cohort 385 non-cancer 46 patients. Combining features, clinical factors, CEA levels, followed by CT imaging, detected 94% patients with across stages subtypes,...
Abstract Liver cancer is a major cause of mortality worldwide. Screening individuals at high risk, including those with cirrhosis and viral hepatitis, provides an avenue for improved survival, but current screening methods are inadequate. In this study, we used whole-genome cell-free DNA (cfDNA) fragmentome analyses to evaluate 724 from the United States, European Union, or Hong Kong hepatocellular carcinoma (HCC) who were average high-risk HCC. Using machine learning model that incorporated...
With the advent of precision oncology, there is an urgent need to develop improved methods for rapidly detecting responses targeted therapies. Here, we have developed ultrasensitive measure cell-free tumor load using and whole-genome sequencing approaches assess tyrosine kinase inhibitors in patients with advanced lung cancer. Analyses 28 treated anti-EGFR or HER2 therapies revealed a bimodal distribution circulating DNA (ctDNA) after therapy initiation, molecular responders having nearly...
Somatic mutations are a hallmark of tumorigenesis and may be useful for non-invasive diagnosis cancer. We analyzed whole-genome sequencing data from 2,511 individuals in the Pan-Cancer Analysis Whole Genomes (PCAWG) study as well 489 four prospective cohorts found distinct regional mutation type-specific frequencies tissue cell-free DNA patients with cancer that were associated replication timing other chromatin features. A machine-learning model using genome-wide mutational profiles...
Circulating cell-free DNA (cfDNA) is emerging as an avenue for cancer detection, but the characteristics of cfDNA fragmentation in blood are poorly understood. We evaluate effect methylation and gene expression on genome-wide through analysis 969 individuals. fragment ends more frequently contained CCs or CGs, fragments ending with CGs CCGs enriched depleted, respectively, at methylated CpG positions. Higher levels larger sizes associated reduced expression. These effects validated mice...
Abstract Circulating cell-free DNA (cfDNA) assays for monitoring individuals with cancer typically rely on prior identification of tumor-specific mutations. Here, we develop a tumor-independent and mutation-independent approach (DELFI-tumor fraction, DELFI-TF) using low-coverage whole genome sequencing to determine the cfDNA tumor fraction validate method in two independent cohorts patients colorectal or lung cancer. DELFI-TF scores strongly correlate circulating levels (ctDNA) (r = 0.90, p...
Abstract Ovarian cancer is a leading cause of death for women worldwide, in part due to ineffective screening methods. In this study, we used whole-genome cell-free DNA (cfDNA) fragmentome and protein biomarker [cancer antigen 125 (CA-125) human epididymis 4 (HE4)] analyses evaluate 591 with ovarian cancer, benign adnexal masses, or without lesions. Using machine learning model the combined features, detected specificity >99% sensitivities 72%, 69%, 87%, 100% stages I IV,...
The diagnostic workup of individuals suspected having lung cancer can be complex and protracted because conventional symptoms have low specificity sensitivity.Among with cancer, a blood-based approach to analyze cell-free DNA (cfDNA) fragmentation (the evaluation fragments for early interception [DELFI] score) enhance the possible presence cancer?Adults were referred Bispebjerg Hospital (Copenhagen, Denmark) initial imaging anomalies consistent cancer. Numbers types extracted from medical...
<p>Supplementary Figure S1. Evaluation of screening model DELFI-Pro scores and comorbidities in individuals without cancer. Supplementary S2. score evaluation available clinical characteristics patients with S3. Stability analysis across fold repeats collection source. S4. Detection ovarian cancer subtypes using model. S5. ROC analyses asymptomatic the or diagnostic models Discovery Cohort. S6. Performance ichorCNA median cfDNA fragment lengths Cohorts. S7. at high specificity. S8....
<div>Abstract<p>Ovarian cancer is a leading cause of death for women worldwide, in part due to ineffective screening methods. In this study, we used whole-genome cell-free DNA (cfDNA) fragmentome and protein biomarker [cancer antigen 125 (CA-125) human epididymis 4 (HE4)] analyses evaluate 591 with ovarian cancer, benign adnexal masses, or without lesions. Using machine learning model the combined features, detected specificity >99% sensitivities 72%, 69%, 87%, 100% stages I...
Abstract Diagnostic delays in patients with brain cancer are common and can impact patient outcome. Development of a blood-based assay for detection cancers could accelerate diagnosis. In this study, we analyzed genome-wide cell-free (cfDNA) fragmentomes, including fragmentation profiles repeat landscapes, from the plasma individuals (n=148) or without (n=357) cancer. Machine learning analyses cfDNA fragmentome features detected across all grade gliomas (AUC=0.90, 95% CI: 0.87-0.93) these...
Determining response to therapy for patients with pancreatic cancer can be challenging. We evaluated methods assessing therapeutic using cell-free DNA (cfDNA) in plasma from metastatic the CheckPAC trial (NCT02866383). Patients were before and after initiation of tumor-informed whole-genome sequencing (WGMAF) tumor-independent genome-wide cfDNA fragmentation profiles repeat landscapes (ARTEMIS-DELFI). Using WGMAF, molecular responders had a median overall survival (OS) 319 days compared 126...
8074 Background: Liquid biopsies provide an opportunity for non-invasive lung cancer detection and tumor subtyping when tissue is not available. Here we evaluate a blood-based liquid biopsy approach its relationship to clinical subtype characteristics of cases using cohort 578 individuals from prospective trial (LEMA, NCT02894853). Methods: Pre-treatment plasma samples were processed the DELFI assay, cell-free DNA (cfDNA) genome-wide fragmentomics based machine learning classifier. Clinical...
Hyperuricemia is associated with multiple diseases, including gout, cardiovascular disease, and renal disease. Serum urate highly heritable, yet association studies of single nucleotide polymorphisms (SNPs) serum uric acid explain a small fraction the heritability. Whether copy number (CNPs) contribute to levels unknown. We assessed on genome-wide scale among 8,411 individuals European ancestry (EA) who participated in Atherosclerosis Risk Communities (ARIC) study. CNPs upstream transporter...
ABSTRACT By sequencing the exomes of distantly related individuals in multiplex families, rare mutational and structural changes to coding DNA can be characterized their relationship disease risk assessed. Recently, several single nucleotide variants (SNVs) were associated with an increased nonsyndromic oral cleft, highlighting importance sequence clefts illustrating strength family‐based study designs. However, extent which deletions regions genome occur contribute is not well understood....
Abstract Noninvasive approaches for detection of tumor-specific mutations in cell-free DNA (cfDNA) have the potential to track a patient’s response treatment, enabling effective and timely decisions on therapy. However, cfDNA arising from clonal hematopoeisis (CH) are common tumor biopsies definitive identification origin these not always available. Sequencing matched cells buffy coat absence has been used rule-out white blood cell (WBC) mutations, but uneven sequencing depths between...
8519 Background: Lung cancer incidence and mortality are increasing worldwide despite more effective treatments. This is primarily due to the late stage of diagnosis when treatments less effective. Although large randomized trials have demonstrated a significant decrease in lung through screening high-risk individuals with chest low dose computed tomography (LDCT), LDCT has made little impact community, mainly lack accessibility. There therefore an unmet clinical need for development...
Abstract Introduction: Ovarian cancer is the leading cause of death from gynecological related cancers worldwide. Most patients are diagnosed at late stages due to asymptomatic disease and lack effective screening modalities. Additionally, in women with an ovarian mass diagnosis can be challenging many having surgery only discover a benign pathology. Liquid biopsies, including analyses cell-free DNA (cfDNA) fragmentomes circulation, have shown promise for early detection may provide useful...
Genome-wide association studies (GWAS) using single nucleotide polymorphisms (SNPs) have identified more than 50 loci associated with estimated glomerular filtration rate (eGFR), a measure of kidney function. However, significant SNPs account for small proportion eGFR variability. Other forms genetic variation not been comprehensively evaluated eGFR. In this study, we assess whether changes in germline DNA copy number are GFR from serum creatinine, eGFRcrea. We used hidden Markov models...
Abstract Cell-free DNA (cfDNA) in the bloodstream is increasingly gaining attention as a diagnostic tool for early detection of cancer. Nevertheless, characteristics and sources cfDNA fragmentation blood remain poorly understood. In this study, we sought to unravel impact methylation gene expression on naturally occurring genome-wide cfDNA. We performed comprehensive analysis plasma samples from 969 individuals, including 182 individuals diagnosed with cancer (pancreatic, colorectal,...
Abstract Introduction: Pancreatic cancer has a poor prognosis especially when identified at advanced stages. Globally in 2020, &gt;450,000 people died from the disease. For those with locally or metastatic cancer, standard of care treatment is chemotherapy. Preliminary studies show that some patients advanced-stage disease respond to immune checkpoint blockade treatment. Determining response therapy using imaging techniques can be challenging. There clinical unmet need for noninvasive...
Abstract INTRODUCTION: Clonal hematopoiesis (CH) is the result of clonal expansion hematopoietic stem cells which acquire and pass on somatically gained mutations, including SNVs as well arm level losses gains, defined here mosaic deletions amplifications (mDAs). The proportion blood in circulation containing CH alterations increases with age environmental exposures such smoking, leading to a higher prevalence many high-risk cancer screening populations. remains major confounder for...