Integrated multiomics signatures to optimize the accurate diagnosis of lung cancer

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 2, 2025

Diagnosing lung cancer from indeterminate pulmonary nodules (IPLs) remains challenging. In this multi-institutional study involving 2032 participants with IPLs, we integrate the clinical, radiomic circulating cell-free DNA fragmentomic features in 5-methylcytosine (5mC)-enriched regions to establish a multiomics model (clinic-RadmC) for predicting malignancy risk of IPLs. The clinic-RadmC yields an area-under-the-curve (AUC) 0.923 on external test set, outperforming single-omics models, and models that only combine clinical radiomic, or 5mC-enriched (p < 0.050 all). superiority maintains well even after adjusting clinic-radiological variables. Furthermore, clinic-RadmC-guided strategy could reduce unnecessary invasive procedures benign IPLs by 10.9% ~ 35%, avoid delayed treatment 3.1% 38.8%. summary, our indicates provides more effective noninvasive tool optimizing diagnoses, thus facilitating precision interventions. Diagnosis Here, authors develop multi-omics signature identify oncogenic nodules, prevent procedures.

Language: Английский

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Integrating multi‐omics features enables non‐invasive early diagnosis and treatment response prediction of diffuse large B‐cell lymphoma

Clinical and Translational Medicine, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 1, 2025

Abstract Background Multi‐omics features of cell‐free DNA (cfDNA) can effectively improve the performance non‐invasive early diagnosis and prognosis cancer. However, multimodal characterization cfDNA remains technically challenging. Methods We developed a comprehensive multi‐omics solution (COMOS) to specifically obtain an extensive fragmentomics landscape, presented by breakpoint characteristics nucleosomes, CpG islands, DNase clusters enhancers, besides typical methylation, copy number alteration cfDNA. The COMOS was tested on 214 plasma samples diffuse large B‐cell lymphoma (DLBCL) matched healthy controls. Results For diagnosis, improved area under curve (AUC) value .993 compared with individual omics model, sensitivity 95% at 98% specificity. Detection achieved 91% 99% specificity in early‐stage patients, while AUC values model were 0.942, 0.968, 0.989, 0.935, 0.921, 0.781 0.917, respectively, lower In treatment response cohort, yielded superior 88% 86% (AUC, 0.903). has excellent prediction. Conclusions Our study provides approach high accuracy for DLBCL, showing great potential future clinical application. Key points A Integrated could be used DLBCL. evaluate efficacy R‐CHOP before DLBCL treatment.

Language: Английский

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Artificial intelligence and machine learning in cell-free-DNA-based diagnostics

Genome Research, Journal Year: 2025, Volume and Issue: 35(1), P. 1 - 19

Published: Jan. 1, 2025

The discovery of circulating fetal and tumor cell-free DNA (cfDNA) molecules in plasma has opened up tremendous opportunities noninvasive diagnostics such as the detection chromosomal aneuploidies cancers posttransplantation monitoring. advent high-throughput sequencing technologies makes it possible to scrutinize characteristics cfDNA molecules, opening fields genetics, epigenetics, transcriptomics, fragmentomics, providing a plethora biomarkers. Machine learning (ML) and/or artificial intelligence (AI) that are known for their ability integrate high-dimensional features have recently been applied field liquid biopsy. In this review, we highlight various AI ML approaches cfDNA-based diagnostics. We first introduce biology basic concepts technologies. then discuss selected examples ML- or AI-based applications prenatal testing cancer These include deduction fraction, tissue mapping, localization. Finally, offer perspectives on future direction using leverage fragmentation patterns terms methylomic transcriptional investigations.

Language: Английский

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Genomic and fragmentomic landscapes of cell-free DNA for early cancer detection

Nature reviews. Cancer, Journal Year: 2025, Volume and Issue: unknown

Published: March 4, 2025

Language: Английский

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Multimodal analysis of methylomics and fragmentomics in plasma cell-free DNA for multi-cancer early detection and localization

eLife, Journal Year: 2023, Volume and Issue: 12

Published: July 25, 2023

Despite their promise, circulating tumor DNA (ctDNA)-based assays for multi-cancer early detection face challenges in test performance, due mostly to the limited abundance of ctDNA and its inherent variability. To address these challenges, published date demanded a very high-depth sequencing, resulting an elevated price test. Herein, we developed multimodal assay called SPOT-MAS (screening presence by methylation size) simultaneously profile methylomics, fragmentomics, copy number, end motifs single workflow using targeted shallow genome-wide sequencing (~0.55×) cell-free DNA. We applied 738 non-metastatic patients with breast, colorectal, gastric, lung, liver cancer, 1550 healthy controls. then employed machine learning extract multiple cancer tissue-specific signatures detecting locating cancer. successfully detected five types sensitivity 72.4% at 97.0% specificity. The sensitivities early-stage cancers were 73.9% 62.3% stages I II, respectively, increasing 88.3% stage IIIA. For tumor-of-origin, our achieved accuracy 0.7. Our study demonstrates comparable performance other ctDNA-based while requiring significantly lower depth, making it economically feasible population-wide screening.

Language: Английский

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Circulating tumor DNA methylation detection as biomarker and its application in tumor liquid biopsy: advances and challenges

MedComm, Journal Year: 2024, Volume and Issue: 5(11)

Published: Nov. 1, 2024

Abstract Circulating tumor DNA (ctDNA) methylation, an innovative liquid biopsy biomarker, has emerged as a promising tool in early cancer diagnosis, monitoring, and prognosis prediction. As noninvasive approach, overcomes the limitations of traditional tissue biopsy. Among various biomarkers, ctDNA methylation garnered significant attention due to its high specificity detection capability across diverse types. Despite immense potential, clinical application faces substantial challenges pertaining sensitivity, specificity, standardization. In this review, we begin by introducing basic biology common techniques methylation. We then explore recent advancements faced biopsies. This includes progress screening identification molecular subtypes, monitoring recurrence minimal residual disease (MRD), prediction treatment response prognosis, assessment burden, determination origin. Finally, discuss future perspectives applications. comprehensive overview underscores vital role enhancing diagnostic accuracy, personalizing treatments, effectively progression, providing valuable insights for research practice.

Language: Английский

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Multicancer Detection (MCD) Testing in Gastrointestinal Cancers: An Evolving Tool for Early Diagnosis

Current Gastroenterology Reports, Journal Year: 2025, Volume and Issue: 27(1)

Published: March 6, 2025

The current review aims to summarize the benefits and limitations of novel multicancer detection tests (MCD) for diagnosing gastrointestinal (GI) malignancies. Traditional cancer screening methods can reduce deaths in malignancies involving GI tract. For cancers, options vary by type often involve invasive techniques with limited sensitivity. MCDs offer a promising, non-invasive (simple blood draw) alternative analyzing biomarkers such as cell-free DNA RNA using advanced machine learning detect cancers across multiple organ sites. Large studies like PATHFINDER trial THUNDER study have demonstrated feasibility accuracy MCD assays identifying signals, high sensitivity specificity some organs that lack routine (e.g., liver, pancreas, stomach). Despite these advancements, testing faces challenges, including costs, FDA approval, false positives, data on clinical utility reducing cancer-specific mortality. should not be substitute age-appropriate screenings but may complement existing methods, particularly no tools, cholangiocarcinoma pancreatic cancer. Clinicians need discuss MCDs, potential overdiagnosis, patient anxiety, financial burden due insurance coverage gaps. is test augment traditional screening. As role evolves, further research essential establish how it will integrated into practice, ensuring informed, shared decision-making patients.

Language: Английский

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A deep-learning model for quantifying circulating tumour DNA from the density distribution of DNA-fragment lengths

Nature Biomedical Engineering, Journal Year: 2025, Volume and Issue: unknown

Published: March 7, 2025

Language: Английский

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Decoding the Dynamics of Circulating Tumor DNA in Liquid Biopsies

Cancers, Journal Year: 2024, Volume and Issue: 16(13), P. 2432 - 2432

Published: July 1, 2024

Circulating tumor DNA (ctDNA), a fragment of found in the bloodstream, has emerged as revolutionary tool cancer management. This review delves into biology ctDNA, examining release mechanisms, including necrosis, apoptosis, and active secretion, all which offer information about state nature tumor. Comprehensive profiling been enabled by methods such whole genome sequencing methylation analysis. The low abundance ctDNA fraction makes alternative techniques, digital PCR targeted next-generation exome sequencing, more valuable accurate for mutation detection. There are numerous clinical applications analysis, non-invasive liquid biopsies minimal residual disease monitoring to detect recurrence, personalized medicine therapy identification, early detection, real-time evaluation therapeutic response. Integrating analysis routine practice creates promising avenues successful care, from diagnosis treatment follow-up.

Language: Английский

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Prediction of methylation status using WGS data of plasma cfDNA for multi-cancer early detection (MCED)

Clinical Epigenetics, Journal Year: 2024, Volume and Issue: 16(1)

Published: Feb. 27, 2024

Abstract Background Cell-free DNA (cfDNA) contains a large amount of molecular information that can be used for multi-cancer early detection (MCED), including changes in epigenetic status cfDNA, such as cfDNA fragmentation profile. The is non-random and may related to methylation. This study provides clinical evidence the feasibility inferring methylation levels based on patterns. We performed whole-genome bisulfite sequencing (WGS) both healthy individuals cancer patients. Using levels, we investigated cytosine–phosphate–guanine (CpG) cleavage profile validated method predicting level individual CpG sites using WGS data. Results conducted biomarker analysis data from obtained unique or shared potential biomarkers each group built models accordingly. modeling results proved predict single model Conclusion By combining with machine learning algorithms, have identified specific sites. Therefore, profile, widely biomarker, assay MCED.

Language: Английский

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