Tissue-Specific Methylation Biosignatures for Monitoring Diseases: An In Silico Approach
Abstract
:1. Introduction
2. Results
2.1. Breast Cancer
2.1.1. Differential Methylation Analysis Comparing BrCa and Healthy Tissues
2.1.2. Functional Analysis of DMGs Comparing BrCa and Healthy Tissues
2.1.3. BrCa-Specific Methylation Biosignature through AutoML
2.1.4. Validation and Applicability of BrCa-Specific Methylation Biosignature on ccfDNA
2.1.5. Biological Relevance of Genes Selected in the BrCa-Specific Methylation Biosignature
2.2. Osteoarhtitis
2.2.1. Differential Methylation Analysis Comparing OA and Healthy Tissues
2.2.2. Functional Analysis of DMGs Comparing OA and Healthy Tissues
2.2.3. OA Specific Methylation Biosignature through AutoML
2.2.4. Biological Relevance of Genes Selected in the OA-Specific Methylation Biosignature
2.3. Diabetes
2.3.1. Differential Methylation Analysis Comparing Pancreatic β-Cells and Other Tissues
2.3.2. Functional Analysis of DMGs Comparing Pancreatic β-Cells and Other Tissues
2.3.3. Pancreatic β-Cell Specific Methylation Biosignature Using AutoML
2.3.4. Biological Relevance of Genes Selected in the β-Cell-Specific Methylation Biosignature
3. Discussion
4. Materials and Methods
4.1. Data Sources
4.2. Data Preprocessing and Differential Methylation Analysis
4.3. Automated Machine Learning Analysis (AutoML)
4.4. Biological Association Analysis through Text Mining
4.5. Functional Analysis of DMGs
4.6. Evaluation of Biosignatures on Liquid Biopsy
4.7. 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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Signature Genes | Gene Type | Description | Pathway | GO—Molecular Function | GO—Cellular Components | GO—Biological Process | UniReD Score | Methylation in BrCa in Relation to Healthy Tissues |
---|---|---|---|---|---|---|---|---|
CCDC181 | Protein Coding | Coiled-Coil Domain Containing 181 | NA | microtubule binding | manchette, cytoplasm, cytoskeleton, microtubule, cilium | NA | 5 | Hypermethylation |
HIST2H3PS2 | Protein Coding | Histone Cluster 2, H3, Pseudogene 2 | NA | DNA binding, protein heterodimerization activity | Nucleus, Chromosome | NA | 1 | Hypermethylation |
RUVBL1-AS1 | RNA Gene | RUVBL1 Antisense RNA 1 | NA | NA | NA | NA | NA | Hypermethylation |
CFTR | Protein Coding | CF Transmembrane Conductance Regulator | CDK-mediated phosphorylation and removal of Cdc6, bacterial infections in CF airways, regulation of CFTR activity, salivary secretion | nucleotide binding, chloride channel activity, intracellularly ATP-gated chloride channel activity | nucleus, cytoplasm, lysosomal membrane, endsome, early endsome | cholesterol biosynthetic process, ion transport, chloride transport, vesicle docking involved in exocytes | 7 | Hypermethylation |
AL161908.1 | RNA Gene | Novel Transcript, Antisense To LIM1B | NA | NA | NA | NA | NA | Hypermethylation |
Signature Genes | Gene Type | Description | Pathway | GO—Molecular Function | GO—Cellular Components | GO—Biological Process | UniReD Score | Methylation in OA in Relation to Other Tissues |
---|---|---|---|---|---|---|---|---|
CASD1 | Protein Coding | CAS1 Domain Containing 1 | NA | acetyltransferase activity, transferase activity, transferring acyl groups | Golgi membrane, Golgi apparatus, membrane, integral component of membrane, integral component of Golgi membrane | Carbohydrate metabolic process | 0 | Hypomethylation |
LINC01350 | LncRNA | Long Intergenic Non-Protein Coding RNA 1350 | NA | NA | NA | NA | NA | Hypomethylation |
RP11-515E23.2 | NA | NA | NA | NA | NA | NA | NA | Hypomethylation |
STOML1 | Protein Coding | Stomatin-Like 1 | NA | protein binding | endosome, plasma membrane, membrane, integral component of membrane | lipid transport | 2.5 | Hypomethylation |
CARMAL | RNA Gene | Coronary Artery Disease Region-Linked MFGE8 Regulatory LncRNA | NA | NA | NA | NA | NA | Hypomethylation |
RP11-272L13.3 | LncRNA | NA | NA | NA | NA | NA | NA | Hypomethylation |
Signature Genes | Gene Type | Description | Pathway | GO—Molecular Function | GO—Cellular Components | GO—Biological Process | UniReD Score | Methylation in Pancreatic β Cells in Relation to Other Healthy Tissues |
---|---|---|---|---|---|---|---|---|
SCARNA6 | snoRNA | Small Cajal Body-Specific RNA 6 | NA | NA | nucleolus | RNA processing | ΝA | Hypomethylation |
TXNRD3 | Protein Coding | Thioredoxin Reductase 3 | folate metabolism and mechanisms of CFTR activation by S-nitrosoglutathione | nucleotide binding, thioredoxin disulfide reductase activity, electron transfer activity, protein disulfide oxidoreductase activity | cell, nucleoplasm, cytoplasm, endoplasmic reticulum, cytosol | multicellular organism development, spermatogenesis, electron transport chain, cell differentiation | 5.5 | Hypomethylation |
AC008741.1 | lncRNA | Novel Transcript, Antisense To ZKSCAN2 | NA | NA | NA | NA | ΝA | Hypomethylation |
LENG8 | Protein Coding | Leukocyte Receptor Cluster Member | NA | protein binding | nucleus | NA | NA | Hypomethylation |
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Karaglani, M.; Panagopoulou, M.; Baltsavia, I.; Apalaki, P.; Theodosiou, T.; Iliopoulos, I.; Tsamardinos, I.; Chatzaki, E. Tissue-Specific Methylation Biosignatures for Monitoring Diseases: An In Silico Approach. Int. J. Mol. Sci. 2022, 23, 2959. https://doi.org/10.3390/ijms23062959
Karaglani M, Panagopoulou M, Baltsavia I, Apalaki P, Theodosiou T, Iliopoulos I, Tsamardinos I, Chatzaki E. Tissue-Specific Methylation Biosignatures for Monitoring Diseases: An In Silico Approach. International Journal of Molecular Sciences. 2022; 23(6):2959. https://doi.org/10.3390/ijms23062959
Chicago/Turabian StyleKaraglani, Makrina, Maria Panagopoulou, Ismini Baltsavia, Paraskevi Apalaki, Theodosis Theodosiou, Ioannis Iliopoulos, Ioannis Tsamardinos, and Ekaterini Chatzaki. 2022. "Tissue-Specific Methylation Biosignatures for Monitoring Diseases: An In Silico Approach" International Journal of Molecular Sciences 23, no. 6: 2959. https://doi.org/10.3390/ijms23062959