Longitudinal analysis of personal cfDNA methylome patterns in metastatic prostate cancer [plasma]
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PROVIDER: PRJNA660746 | ENA |
REPOSITORIES: ENA
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Project description:Disease progression and therapeutic resistance are hallmarks of advanced stage prostate cancer (PCa), which remains a major cause of cancer-related mortality around the world. Longitudinal studies, coupled with the use of liquid biopsies, offer a potentially new and minimally invasive platform to study the dynamics of tumour progression. Our study aimed to investigate the dynamics of personal methylomic profiles of metastatic PCa (mPCa) patients, during disease progression and therapy administration. 52 plasma samples from 9 patients with mPCa were collected, longitudinally, over 13-21 months. After cell-free DNA (cfDNA) isolation, DNA methylation was profiled using the Infinium MethylationEPIC BeadChip and analysed using the minfi software. The top 5% most variable probes across time, within each individual, were utilised to study dynamic methylation patterns during disease progression and therapeutic response. Statistical testing was carried out to identify and validate ctDNA differentially methylated genes (DMGs). Personal cfDNA global methylation patterns were temporally stable throughout disease course. A proportion of analysed CpG sites presented a dynamic temporal pattern that was consistent with clinical events, such as therapy administration, and were prominently associated with immune response pathways. Study of ctDNA identified >2,000 DMGs with dynamic methylation patterns. We concluded that longitudinal assessment of cfDNA methylation in mPCa patients unveiled dynamic patterns associated with the occurrence of specific clinical events, thus highlighting the potential of using liquid biopsies to study PCa progression.
2021-09-01 | GSE157273 | GEO
Project description:Epigenomics regulates gene expression and is as important as genomics in precision personal health, as it is heavily influenced by environment and lifestyle. We profiled whole genome DNA methylation and corresponding transcriptome of peripheral blood mononuclear cells collected from a human volunteer over a period of 36 months, generating 28 methylome and 57 transcriptome datasets. We found that DNA methylomic changes are associated with infrequent glucose levels alteration, whereas the transcriptome underwent dynamic changes during events such as viral infections. Most DNA meta-methylome changes occurred 80-90 days prior to clinically detectable glucose elevation. Analysis of the deep personal methylome dataset revealed an unprecedented number of allelic differentially methylated regions (aDMR) which remain stable longitudinally and are preferentially associated with allele-specific gene regulation. Our results revealed that different types of "omics" data associate with different aspects of conditions of this individual: DNA methylation with chronic disease and transcriptome with acute events.
2018-10-05 | GSE111405 | GEO
Project description:Longitudinal Personal DNA Methylome Dynamics in a Human with a Chronic Condition
| PRJNA436956 | ENA
Project description:We aimed to clarify the cell-free DNA (cfDNA) physiological role. We exposed THP1 cells to plasma from healthy individuals with and without cfDNA and compared their transcriptomes and proteomes.
2020-12-01 | E-MTAB-8574 | biostudies-arrayexpress
Project description:BackgroundDisease progression and therapeutic resistance are hallmarks of advanced stage prostate cancer (PCa), which remains a major cause of cancer-related mortality around the world. Longitudinal studies, coupled with the use of liquid biopsies, offer a potentially new and minimally invasive platform to study the dynamics of tumour progression. Our aim was to investigate the dynamics of personal DNA methylomic profiles of metastatic PCa (mPCa) patients, during disease progression and therapy administration.ResultsForty-eight plasma samples from 9 mPCa patients were collected, longitudinally, over 13-21 months. After circulating cell-free DNA (cfDNA) isolation, DNA methylation was profiled using the Infinium MethylationEPIC BeadChip. The top 5% most variable probes across time, within each individual, were utilised to study dynamic methylation patterns during disease progression and therapeutic response. Statistical testing was carried out to identify differentially methylated genes (DMGs) in cfDNA, which were subsequently validated in two independent mPCa (cfDNA and FFPE tissue) cohorts. Individual cfDNA global methylation patterns were temporally stable throughout the disease course. However, a proportion of CpG sites presented a dynamic temporal pattern that was consistent with clinical events, including different therapies, and were prominently associated with genes linked to immune response pathways. Additionally, study of the tumour fraction of cfDNA identified > 2000 DMGs with dynamic methylation patterns.ConclusionsLongitudinal assessment of cfDNA methylation in mPCa patients unveiled dynamic patterns associated with disease progression and therapy administration, thus highlighting the potential of using liquid biopsies to study PCa evolution at a methylomic level.
| S-EPMC8403420 | biostudies-literature
Project description:We performed all stimulatory experiments using THP1 cell line as a representative of primary human monocytes to show fundamental role of the cfDNA in healthy organisms. The experiments were conducted in duplicates using plasma containing cfDNA (NP) and the reference one with cfDNA removed by DNase (TP) to recognize unequivocally the effect of plasma cfDNA on transcriptome and proteome of monocytes. We used native human plasma samples obtained from healthy volunteers with no animal serum addition to cultivation medium in order to avoid the presence of uncharacterized animal cfDNA in the experiments.
2021-05-18 | PXD017285 | Pride
Project description:We evaluated whether targeted next-generation sequencing (NGS) using the Ion Torrent Personal Genome Sequencer of cfDNA could identify prognostic or predictive factors for overall survival (OS) or progression free survival (PFS) within a large cohort of patients with advanced lung adenocarcinoma enrolled in the GALAXY-1 trial.
2018-01-10 | E-MTAB-5749 | biostudies-arrayexpress
Project description:The genome-wide analysis of cfDNA fragmentation patterns in DENQCMs and maternal plasma was performed by deep sequencing using Illumina Novaseq to confirm their biological characteristics. We first performed deep whole genome sequencing of the cfDNA extracted from DENQCMs and maternal plasma cfDNA. Then we analyzed the sequencing data and compared various characteristics of cfDNA fragmentation patterns, such as dinucleotide composition, nucleosome protection length, and nucleosome occupancy based on a windowed protection score (WPS), to the submitter-provided processed data from a healthy individual IH01 (GEO accession GSM1833276).
2019-01-05 | GSE124686 | GEO
Project description:We provide the first in vivo evidence of global and local chromatin changes in human aging by analyzing cfDNA from the blood of individuals of different age groups. Our results show that nucleosome signals inferred from cfDNA are consistent with the redistribution of heterochromatin observed in cellular senescence and aging in other model systems. It also revealed age and deteriorating health status correlate with a low-level enrichment of signals from cells in the thyroid gland. In addition, we detected an overall nucleosome loss at several genomic locations, such as transcription start and termination sites, 5’UTR of L1HS retrotransposons and dimeric AluY elements with age.
2018-12-21 | GSE114511 | GEO
Project description:We surveyed the variation and dynamics of active regulatory elements genome-wide in CD4+ T cells, using Assay of Transposase Accessible Chromatin with sequencing (ATAC-seq) in longitudinal samples from healthy volunteers and during T cell activation. We created robust pipelines that enable accurate single molecule counting and allelic discrimination from clinical material. Over 4000 regulatory elements (7.2%) showed reproducible personal variation in activity. Gender was the most significant attributable source of regulome variation. ATAC-seq revealed novel elements that escape X chromosome inactivation and predicted gender-specific gene regulatory networks across autosomes, which coordinately impact genes with immune function. Noisy regulatory elements with personal variation in accessibility are significantly enriched for autoimmune disease loci. Over one third of regulome variation lacked genetic variation in cis, suggesting contributions from environmental or epigenetic factors. These results refine concepts of human individuality and provide foundational reference to compare disease-associated regulomes.
2015-06-23 | GSE60682 | GEO