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Heat selection enables highly scalable methylome profiling in cell-free DNA for noninvasive monitoring of cancer patients [CRC]

ABSTRACT: Heat selection enables highly scalable methylome profiling in cell-free DNA for noninvasive monitoring of cancer patients [CRC]

PROVIDER: PRJNA860193 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR20314900_1.fastq.gz	Fastqsanger.gz
	SRR20314900_2.fastq.gz	Fastqsanger.gz
	SRR20314901_1.fastq.gz	Fastqsanger.gz
	SRR20314901_2.fastq.gz	Fastqsanger.gz
	SRR20314902_1.fastq.gz	Fastqsanger.gz

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Heat selection enables highly scalable methylome profiling in cell-free DNA for noninvasive monitoring of cancer patients [CRC]

Project description:Genome-wide analysis of cell-free DNA (cfDNA) methylation profile has been recognized as a promising approach for sensitive and specific detection of many cancers. However, scaling such genome-wide assays for clinical translation is impractical due to the high cost of whole genome bisulfite sequencing. We have shown that the small fraction of GC-rich genome is highly enriched in CpG sites and disproportionately harbors the majority of cancer-specific methylation signature. Here, we report on the simple but effective Heat enrichment of CpG-rich regions for Bisulfite Sequencing (Heatrich-BS) platform that allows for focused methylation profiling in these highly informative regions. Our novel method and bioinformatics algorithm enable accurate tumor burden estimation with high sensitivity and quantitative tracking of colorectal cancer patient’s response to treatment, at much reduced sequencing cost suitable for frequent monitoring. We also show, for the first time, tumor epigenetic subtyping from cfDNA using Heatrich-BS, which could enable patient stratification from non-invasive liquid biopsy. As such, Heatrich-BS holds great potential for highly scalable screening and regular monitoring of cancer using liquid biopsy.

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Heat selection enables highly scalable methylome profiling in cell-free DNA for noninvasive monitoring of cancer patients

2022-05-13 | GSE202606 | GEO

Heat selection enables highly scalable methylome profiling in cell-free DNA for noninvasive monitoring of cancer patients

Project description:Heat selection enables highly scalable methylome profiling in cell-free DNA for noninvasive monitoring of cancer patients

| PRJNA836767 | ENA

Heat selection enables highly scalable methylome profiling in cell-free DNA for noninvasive monitoring of cancer patients

Project description:Genome-wide analysis of cell-free DNA (cfDNA) methylation profile has been recognized as a promising approach for sensitive and specific detection of many cancers. However, scaling such genome-wide assays for clinical translation is impractical due to the high cost of whole genome bisulfite sequencing. We have shown that the small fraction of GC-rich genome is highly enriched in CpG sites and disproportionately harbors the majority of cancer-specific methylation signature. Here, we report on the simple but effective Heat enrichment of CpG-rich regions for Bisulfite Sequencing (Heatrich-BS) platform that allows for focused methylation profiling in these highly informative regions. Our novel method and bioinformatics algorithm enable accurate tumor burden estimation with high sensitivity and quantitative tracking of colorectal cancer patientÃ¢Â€Â™s response to treatment, at much reduced sequencing cost suitable for frequent monitoring. We also show, for the first time, tumor epigenetic subtyping from cfDNA using Heatrich-BS, which could enable patient stratification from non-invasive liquid biopsy. As such, Heatrich-BS holds great potential for highly scalable screening and regular monitoring of cancer using liquid biopsy.

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Heat selection enables highly scalable methylome profiling in cell-free DNA for noninvasive monitoring of cancer patients.

Project description:Genome-wide analysis of cell-free DNA methylation profile is a promising approach for sensitive and specific detection of many cancers. However, scaling such assays for clinical translation is impractical because of the high cost of whole-genome bisulfite sequencing. We show that the small fraction of GC-rich genome is highly enriched in CpG sites and disproportionately harbors most of the cancer-specific methylation signature. Here, we report on the simple and effective heat enrichment of CpG-rich regions for bisulfite sequencing (Heatrich-BS) platform that allows for focused methylation profiling in these highly informative regions. Our novel method and bioinformatics algorithm enable accurate tumor burden estimation and quantitative tracking of colorectal cancer patient's response to treatment at much reduced sequencing cost suitable for frequent monitoring. We also show tumor epigenetic subtyping using Heatrich-BS, which could enable patient stratification. Heatrich-BS holds great potential for highly scalable screening and monitoring of cancer using liquid biopsy.

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Transplant tissue specfic exosome platform for noninvasive monitoring of immunologic rejection

Project description:Transplant tissue specfic exosome platform for noninvasive monitoring of immunologic rejection

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Multiplexed Perturbation Enables Scalable Pooled Screens

Project description:Multiplexed Perturbation Enables Scalable Pooled Screens

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CRC

Project description:CRC Metagenome

| PRJNA1289688 | ENA

Transplant tissue specfic exosome platform for noninvasive monitoring of immunologic rejection [miRNA]

Project description:In transplantation, there is a critical need for non-invasive biomarker platforms for monitoring immunologic rejection. We hypothesized that transplanted tissues release donor specific exosomes into recipient circulation/ bodily fluids, and that the quantitation and profiling of their intra-exosomal cargoes would constitute a novel biomarker platform for monitoring rejection. We tested this hypothesis in a human into mouse xenogeneic islet transplant model, and validated the concept in clinical settings of islet and renal transplantation. In the xenogeneic model, islet transplant exosomes in recipient blood were quantified over long-term follow-up using anti-human leukocyte antigen (HLA) antibody that is only expressed on human islets (p=1.6x10-14). Transplant islet exosomes were purified using anti-HLA antibody conjugated beads and their cargoes contained bona fide islet endocrine hormone markers insulin, glucagon, and somatostatin. Rejection led to significant decrease in transplant islet exosome signal (p=4x10-15), along with distinct changes in its microRNA and proteomic profiles prior to appearance of hyperglycemia. In the clinical settings of islet (n=5) and renal (n=5) transplantation, donor exosomes with respective tissue specificity for islet β cells and renal epithelial cells were reliably characterized in recipient plasma over follow-up (up to 5 years; p=0.0001). Collectively, these findings demonstrate the biomarker potential of transplant exosome characterization for providing a non-invasive window into the conditional state of the transplant tissue.

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