Dynamic Epigenetic Changes during a Relapse and Recovery Cycle in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
Abstract
:1. Introduction
2. Results
2.1. Study Design and Participants
2.2. Dynamic Analysis of DNA Methylation Variation
2.3. Common ME-iVMFs Methylation Patterns in Patients
2.4. Identifying Methylation Pattern Associated with the Relapse Condition
2.5. Relapse Associated Methylation Signature Exhibits Striking Variation Compared to Control
2.6. Simulated Relapses for the Control Subject Identified Fewer Variable Methylated Genes Than the Patients
3. Discussion
3.1. Benefits of DNA Methylation for a Precision Investigation of ME/CFS
3.2. Inter-Individual Differences Indicate Increased Epigenetic Variation Linked to Disease Severity
3.3. Intra-Individual Variation Identifies Regulatory Regions
3.4. Immune and Inflammatory Changes Implicated in Relapse-Recovery Cycle
4. Materials and Methods
4.1. Cohort Recruitment
4.2. PBMC Isolation
4.3. DNA Extraction
4.4. Generating Methylation Map Using RRBS
4.5. High-Throughput Sequencing
4.6. DNA Methylation and Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Frag | Chr | Start | End | Position | GeneID | Genehancer | Regulatory Interactions | P1-a | P1-b | P1-c | P1-d | P1-e |
---|---|---|---|---|---|---|---|---|---|---|---|---|
1 | 19 | 33,885,306 | 33,885,381 | On Intron | PEPD | GH09J033388 | CEBPG:PEPD | 78 | 45 | 44 | 71 | 64 |
2 | X | 150,565,438 | 150,565,527 | On Intron | VMA21 | GH0XJ151395 | VMA21 | 50 | 33 | 31 | 45 | 49 |
3 | 19 | 55,464,080 | 55,464,189 | On Intron | NLRP7 | GH19J054952 | NLRP2 | 78 | 55 | 48 | 81 | 75 |
4 | 7 | 5,741,705 | 5,741,780 | On Intron | NF216 | GH07J005687 | ACTB:CCZ1:RNF216:USP42 | 86 | 60 | 74 | 84 | 88 |
5 | X | 135,579,269 | 135,579,310 | On Intron | HTATSF1 | - | - | 39 | 28 | 22 | 46 | 40 |
6 | X | 152,908,188 | 152,908,279 | On Intron | DUSP9 | - | DUSP9 | 46 | 18 | 30 | 37 | 45 |
7 | 17 | 45,925,149 | 45,925,204 | On Exon | SP6 | GH17J047846 | SP2:CDK5RAP3: OSBPL7:SCRN2 | 46 | 28 | 29 | 46 | 44 |
8 | X | 23,761,294 | 23,761,378 | On Exon | ACOT9 | GH0XJ023741 | ACOT9 | 37 | 18 | 18 | 34 | 37 |
9 | 8 | 145,003,618 | 145,003,684 | On Exon | PLEC | GH08J143914 | ZC3H3:EEF1D:PLEC | 70 | 34 | 37 | 58 | 59 |
10 | X | 149,106,531 | 149,106,576 | On Exon | CXorf40B | GH0XJ149937 | INC00B94:CXorf40B | 48 | 28 | 36 | 54 | 58 |
11 | 22 | 42,316,243 | 42,316,306 | Intergenic | - | GH22J041918 | WBP2NL:CYP2D8P:CENPM:CYPSD6:TNFRSF13C | 44 | 30 | 27 | 44 | 44 |
12 | 1 | 17,199,256 | 17,199,369 | Intergenic | - | - | NECAP2:CROCC | 55 | 35 | 44 | 59 | 57 |
13 | 2 | 232,348,597 | 232,348,713 | Intergenic | - | - | NMUR1:NCL | 57 | 38 | 34 | 69 | 62 |
14 | 13 | 114,918,456 | 114,918,525 | Intergenic | - | - | CDC16:UPF31: RASA3 | 87 | 65 | 62 | 96 | 84 |
15 | 2 | 26,521,360 | 26,521,433 | Intergenic | - | GH02J026298 | HADHB:HADHA: ADGRF3 | 53 | 38 | 35 | 60 | 53 |
16 | 3 | 10,334,731 | 10,334,778 | Intergenic | - | GH03J010291 | GHRLOS:GHRL | 33 | 13 | 22 | 40 | 41 |
17 | 15 | 22,095,431 | 22,095,475 | Intergenic | - | - | - | 51 | 40 | 34 | 51 | 56 |
Frag | Chr | Start | End | Location | GeneID | Genehancer | Regulatory Interactions | P2-a | P2-b | P2-c | P2-d | P2-e |
---|---|---|---|---|---|---|---|---|---|---|---|---|
1 | 19 | 4,543,716 | 4,543,762 | On Intron | SEMA6B | GH19J004539 | YJU2:PLIN5:SEMA6B:LRG1 | 80 | 81 | 47 | 91 | 67 |
2 | X | 15,353,393 | 15,353,501 | On Intron | PIGA | GH0XJ015333 | ZRSR2:PIGA | 40 | 41 | 18 | 39 | 33 |
3 | 22 | 17,640,812 | 17,640,923 | On Intron | CECR5 | GH22J017157 | HDHD5 | 69 | 82 | 60 | 80 | 71 |
4 | 14 | 105,936,238 | 105,936,292 | On Exon | MTA1 | GH14J105464 | IGHGP:CDCA4:CRIP2:MTA1:ENSG00000257270 | 84 | 80 | 63 | 87 | 76 |
5 | 22 | 18,027,985 | 18,028,072 | On Exon | CECR2 | - | - | 49 | 46 | 68 | 38 | 51 |
6 | X | 102,565,776 | 102,565,848 | Intron–Exon Boundary | BEX2 | GH0XJ103310 | BEX2 | 42 | 45 | 26 | 43 | 41 |
7 | 1 | 155,098,923 | 155,098,964 | Intergenic | - | GH01J155123 | DAP3:CLK2:DPM3:GBAP1:THBS3:EFNA1 | 54 | 67 | 35 | 72 | 60 |
8 | 3 | 10,334,731 | 10,334,778 | Intergenic | - | GH03J010291 | GHRLOS:GHRL | 49 | 56 | 32 | 61 | 41 |
9 | 9 | 38,687,682 | 38,687,760 | Intergenic | - | - | - | 61 | 62 | 39 | 65 | 42 |
10 | 7 | 100,882,140 | 100,882,220 | Intergenic | - | GH07J101231 | FIS1:CLDN15 | 80 | 80 | 65 | 90 | 75 |
11 | 2 | 219,233,608 | 219,233,704 | Intergenic | - | GH02J218366 | AAMP:SCL11A1:TMBIM1:CATIP | 49 | 55 | 38 | 62 | 52 |
12 | 6 | 170,403,979 | 170,404,085 | Intergenic | - | - | WDR27 | 62 | 66 | 81 | 63 | 70 |
13 | X | 129,299,533 | 129,299,622 | Intergenic | - | GH0XJ130164 | ELF4:AIMF1:ZNF280C | 42 | 36 | 61 | 31 | 49 |
14 | X | 135,579,192 | 135,579,268 | Intergenic | - | - | - | 28 | 27 | 61 | 30 | 44 |
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Helliwell, A.M.; Stockwell, P.A.; Edgar, C.D.; Chatterjee, A.; Tate, W.P. Dynamic Epigenetic Changes during a Relapse and Recovery Cycle in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Int. J. Mol. Sci. 2022, 23, 11852. https://doi.org/10.3390/ijms231911852
Helliwell AM, Stockwell PA, Edgar CD, Chatterjee A, Tate WP. Dynamic Epigenetic Changes during a Relapse and Recovery Cycle in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. International Journal of Molecular Sciences. 2022; 23(19):11852. https://doi.org/10.3390/ijms231911852
Chicago/Turabian StyleHelliwell, Amber M., Peter A. Stockwell, Christina D. Edgar, Aniruddha Chatterjee, and Warren P. Tate. 2022. "Dynamic Epigenetic Changes during a Relapse and Recovery Cycle in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome" International Journal of Molecular Sciences 23, no. 19: 11852. https://doi.org/10.3390/ijms231911852