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| Status |
Public on Jul 01, 2019 |
| Title |
Genome-scale DNA methylation analysis of tissue-of-origin of plasma cell-free DNA |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by high throughput sequencing
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| Summary |
Current methods for mapping the tissue-of-origin of circulating cell-free DNA (cfDNA) are still insufficient. Here, we have extended a previously developed methylated CpG tandems amplification and sequencing (MCTA-Seq) method for quantitative analysis of tissue-of-origin of plasma cfDNA. By comparing paired plasma cfDNA and white blood cell genomic DNA, we have demonstrated that the liver is the major non-hematopoietic tissue contributing to plasma cfDNA in healthy adults, accounting for approximately 2%. Furthermore, we have detected changes in liver-derived DNA in patients with benign liver diseases and increases in pancreas-derived DNA in acute pancreatitis patients. Interestingly, our results suggest that DNA derived from pathological tissues makes a minor contribution to the increased cfDNA in many clinical cases. Finally, we have identified a tissue-specific hypermethylated cfDNA marker located in the intragenic regions of tissue-specifichighlyexpressed genes. This study represents valuable progress in the field of cfDNA and offers promise for clinical research and medical diagnostics using the described method.
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| Overall design |
We performed MCTA-Seq on paired cfDNA and WBC gDNA obtained from 14 healthy individuals to find the significantly differentially methylated CGCGCGGs(dmCGCGCGGs) between plasma and WBC. To obtain the tissue-specific methylation pattern, we performed MCTA-Seq on eight major tissues, including liver, lung, stomach, colon, kidney, pancreas, muscle and skin. We found that most plasma dmCGCGCGGs were hypermethylated in the liver. Next, we sought to quantify the non-hematopoietic tissue DNA fractions in plasma cfDNA using deconvolution analysis. We quantify the tissue DNA fractions in plasma cfDNA from healthy individuals and non-malignant liver disease patients.
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| Contributor(s) |
Liu X, Ren J, Luo N, Wen L, Tang F, Peng J |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Aug 17, 2018 |
| Last update date |
Jul 01, 2019 |
| Contact name |
xiaomeng liu |
| E-mail(s) |
liuxiaomeng90@yeah.net
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| Organization name |
Sichuan Cancer Hospital & Institute, Sichuan Cancer Center
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| Street address |
No.55,Section 4,South Renmin Road
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| City |
Chengdu |
| ZIP/Postal code |
610000 |
| Country |
Colombia |
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| Platforms (3) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
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| Samples (107)
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| Relations |
| BioProject |
PRJNA493114 |
| SRA |
SRP162583 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE118690_all_samples_sumT_mepm.txt.gz |
5.2 Mb |
(ftp)(http) |
TXT |
| GSE118690_nor_samples.txt.gz |
2.3 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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