Simultaneous sequencing of genetic and epigenetic bases in DNA DOI Creative Commons
Jens Füllgrabe,

Walraj Gosal,

Páidí Creed

et al.

Nature Biotechnology, Journal Year: 2023, Volume and Issue: 41(10), P. 1457 - 1464

Published: Feb. 6, 2023

DNA comprises molecular information stored in genetic and epigenetic bases, both of which are vital to our understanding biology. Most sequencing approaches address either genetics or epigenetics thus capture incomplete information. Methods widely used detect bases fail common C-to-T mutations distinguish 5-methylcytosine from 5-hydroxymethylcytosine. We present a single base-resolution methodology that sequences complete the two most cytosine modifications workflow. is copied enzymatically converted. Coupled decoding across original copy strand provides phased digital readout. demonstrated on human genomic cell-free blood sample patient with cancer. The approach accurate, requires low input has simple workflow analysis pipeline. Simultaneous, reading more picture genomes applications throughout biomedicine.

Language: Английский

Cancer biomarkers: Emerging trends and clinical implications for personalized treatment DOI Open Access
Antonio Passaro, Maise Al Bakir, Emily G. Hamilton

et al.

Cell, Journal Year: 2024, Volume and Issue: 187(7), P. 1617 - 1635

Published: March 1, 2024

Language: Английский

Citations

130
Circulating cell-free DNA for cancer early detection DOI Creative Commons
Qiang Gao, Qiang Zeng, Zhijie Wang

et al.

The Innovation, Journal Year: 2022, Volume and Issue: 3(4), P. 100259 - 100259

Published: May 6, 2022

Effective screening modalities are currently available for only a small subset of cancers, and they generally have suboptimal performance with complicated procedures. Therefore, there is an urgent need to develop simple, accurate, non-invasive methods early detection cancers. Genetic epigenetic alterations in plasma circulating cell-free DNA (cfDNA) shown the potential revolutionize cancers facilitate subsequent diagnosis improve survival patients. The medical interest cfDNA assays has been inspired by emerging single- multi-early studies. This review summarizes current technological clinical advances, hopes providing insights into development applications various scenarios. key phases biomarkers highlighted, future developments cfDNA-based liquid biopsies outlined. It hoped that this study can boost integration workflow.

Language: Английский

Citations

121
Early-stage multi-cancer detection using an extracellular vesicle protein-based blood test DOI Creative Commons
Juan Pablo Hinestrosa, Razelle Kurzrock, Jean M. Lewis

et al.

Communications Medicine, Journal Year: 2022, Volume and Issue: 2(1)

Published: March 17, 2022

Detecting cancer at early stages significantly increases patient survival rates. Because lethal solid tumors often produce few symptoms before progressing to advanced, metastatic disease, diagnosis frequently occurs when surgical resection is no longer curative. One promising approach detect early-stage, curable cancers uses biomarkers present in circulating extracellular vesicles (EVs). To explore the feasibility of this approach, we developed an EV-based blood biomarker classifier from EV protein profiles I and II pancreatic, ovarian, bladder cancer.Utilizing alternating current electrokinetics (ACE) platform purify EVs plasma, use multi-marker EV-protein measurements develop a machine learning algorithm that can discriminate cases controls. The ACE isolation method requires small sample volumes, streamlined process permits integration into high-throughput workflows.In case-control pilot study, comparison 139 pathologically confirmed stage representing or patients against 184 control subjects yields area under curve (AUC) 0.95 (95% CI: 0.92 0.97), with sensitivity 71.2% 63.2 78.1) 99.5% (97.0 99.9) specificity. Sensitivity similar both [stage I: 70.5% (60.2 79.0) II: 72.5% (59.1 82.9)]. Detection reaches 95.5% 74.4% ovarian (73.1% Stage IA) 43.8% cancer.This work demonstrates EV-based, multi-cancer test has potential clinical value for detection warrants future expanded studies involving prospective cohorts multi-year follow-up.

Language: Английский

Citations

108
Cell-Free DNA–Based Multi-Cancer Early Detection Test in an Asymptomatic Screening Population (NHS-Galleri): Design of a Pragmatic, Prospective Randomised Controlled Trial DOI Open Access
Richard D Neal, Peter Johnson, Christina A. Clarke

et al.

Cancers, Journal Year: 2022, Volume and Issue: 14(19), P. 4818 - 4818

Published: Oct. 1, 2022

We report the design of NHS-Galleri trial (ISRCTN91431511), aiming to establish whether a multi-cancer early detection (MCED) test that screens asymptomatic individuals for cancer can reduce late-stage incidence. This randomised controlled has invited approximately 1.5 million persons and enrolled over 140,000 from general population England (50–77 years; ≥3 years without diagnosis or treatment; not undergoing investigation suspected cancer). Blood is being collected at up three annual visits. Following baseline blood collection, participants are 1:1 intervention (blood tested by MCED test) control stored) arm. Only in arm with signal detected have results returned referred urgent investigations potential treatment. Remaining both arms stay blinded return their next visit. Participants encouraged continue other NHS screening programmes seek help new unusual symptoms. The primary objective demonstrate statistically significant reduction incidence rate stage III IV cancers diagnosed versus 3–4 after randomisation. will determine clinical utility an test.

Language: Английский

Citations

108
Multi-cancer early detection test in symptomatic patients referred for cancer investigation in England and Wales (SYMPLIFY): a large-scale, observational cohort study DOI Creative Commons
Brian D Nicholson, Jason Oke, Pradeep S. Virdee

et al.

The Lancet Oncology, Journal Year: 2023, Volume and Issue: 24(7), P. 733 - 743

Published: June 20, 2023

Analysis of circulating tumour DNA could stratify cancer risk in symptomatic patients. We aimed to evaluate the performance a methylation-based multicancer early detection (MCED) diagnostic test patients referred from primary care.

Language: Английский

Citations

106
Large-scale pancreatic cancer detection via non-contrast CT and deep learning DOI Creative Commons
Kai Cao, Yingda Xia, Jiawen Yao

et al.

Nature Medicine, Journal Year: 2023, Volume and Issue: 29(12), P. 3033 - 3043

Published: Nov. 20, 2023

Pancreatic ductal adenocarcinoma (PDAC), the most deadly solid malignancy, is typically detected late and at an inoperable stage. Early or incidental detection associated with prolonged survival, but screening asymptomatic individuals for PDAC using a single test remains unfeasible due to low prevalence potential harms of false positives. Non-contrast computed tomography (CT), routinely performed clinical indications, offers large-scale screening, however, identification non-contrast CT has long been considered impossible. Here, we develop deep learning approach, pancreatic cancer artificial intelligence (PANDA), that can detect classify lesions high accuracy via CT. PANDA trained on dataset 3,208 patients from center. achieves area under receiver operating characteristic curve (AUC) 0.986-0.996 lesion in multicenter validation involving 6,239 across 10 centers, outperforms mean radiologist performance by 34.1% sensitivity 6.3% specificity identification, 92.9% 99.9% real-world multi-scenario consisting 20,530 consecutive patients. Notably, utilized shows non-inferiority radiology reports (using contrast-enhanced CT) differentiation common subtypes. could potentially serve as new tool screening.

Language: Английский

Citations

101
Detecting Liver Cancer Using Cell-Free DNA Fragmentomes DOI Creative Commons
Zachariah H. Foda, Akshaya V. Annapragada, Kavya Boyapati

et al.

Cancer Discovery, Journal Year: 2022, Volume and Issue: 13(3), P. 616 - 631

Published: Nov. 18, 2022

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 multifeature data, sensitivity detecting was 88% in average-risk population 98% specificity 85% among 80% specificity. We validated these results independent population. cfDNA fragmentation changes reflected genomic chromatin liver cancer, transcription factor binding sites. These findings provide biological basis patients accessible approach noninvasive detection. Significance: There great need sensitive approaches HCC have developed examining genome-wide features high-performing cost-effective See related commentary Rolfo Russo, p. 532. This article highlighted Issue feature, 517

Language: Английский

Citations

98
Biomarkers for immunotherapy of hepatocellular carcinoma DOI
Tim F. Greten, Augusto Villanueva, Firouzeh Korangy

et al.

Nature Reviews Clinical Oncology, Journal Year: 2023, Volume and Issue: 20(11), P. 780 - 798

Published: Sept. 19, 2023

Language: Английский

Citations

97
The potential of liquid biopsy in the management of cancer patients DOI
Athina Markou,

Eleni Tzanikou,

Evi Lianidou

et al.

Seminars in Cancer Biology, Journal Year: 2022, Volume and Issue: 84, P. 69 - 79

Published: March 21, 2022

Language: Английский

Citations

93
cfDNA methylome profiling for detection and subtyping of small cell lung cancers DOI Creative Commons
Francesca Chemi, Simon P. Pearce, Alexandra Clipson

et al.

Nature Cancer, Journal Year: 2022, Volume and Issue: 3(10), P. 1260 - 1270

Published: Aug. 8, 2022

Small cell lung cancer (SCLC) is characterized by morphologic, epigenetic and transcriptomic heterogeneity. Subtypes based upon predominant transcription factor expression have been defined that, in mouse models lines, exhibit potential differential therapeutic vulnerabilities, with epigenetically distinct SCLC subtypes also described. The clinical relevance of these unclear, due part to challenges obtaining tumor biopsies for reliable profiling. Here we describe a robust workflow genome-wide DNA methylation profiling applied both patient-derived patients' circulating cell-free (cfDNA). Tumor-specific patterns were readily detected cfDNA samples from patients correlated survival outcomes. discriminated between the subtypes, precedent liquid biopsy cfDNA-methylation approach molecularly subtype SCLC. Our data reveal utility as universally applicable sensitive detection, monitoring molecular subtyping

Language: Английский

Citations

84