Skip to content
2000
image of Decoding the Methylome: Insights into the Epigenetic Regulation of Polycystic Ovarian Syndrome through Mitochondrial DNA Methylation

Abstract

Polycystic Ovarian Syndrome (PCOS) imposes significant societal health and economic challenges. The precise determinants behind the global prevalence of PCOS are still poorly understood. However, epigenetic modifications in PCOS, such as DNA methylation, have been recognized as a method by which the environment interacts with the genome. Evidence suggests that changes in mitochondrial (mt)DNA methylation may have a role in the heightened occurrence of PCOS. This article provides a comprehensive overview of nuclear DNA methylation, mitochondrial DNA methylation, and their significance in regulating gene expression. Pre-existing scholarly works shed insight into the complex interaction of DNA methylation and other epigenetic modifications associated with PCOS. In addition, this review gathers a detailed explanation of several methodologies employed to assess alterations in DNA methylation at specific sites and across the nuclear and mitochondrial genomes. Integrating mtDNA methylation alterations may be a promising diagnostic strategy for PCOS, potentially paving the way for novel therapeutic interventions.

Loading

Article metrics loading...

/content/journals/cg/10.2174/0113892029401274251009070350
2025-10-22
2025-11-16
Loading full text...

Full text loading...

References

  1. Bozdag G. Mumusoglu S. Zengin D. Karabulut E. Yildiz B.O. The prevalence and phenotypic features of polycystic ovary syndrome: A systematic review and meta-analysis. Hum. Reprod. 2016 31 12 2841 2855 10.1093/humrep/dew218 27664216
    [Google Scholar]
  2. Christ J.P. Cedars M.I. Current guidelines for diagnosing PCOS. Diagnostics 2023 13 6 1113 10.3390/diagnostics13061113 36980421
    [Google Scholar]
  3. Akre S. Sharma K. Chakole S. Wanjari M.B. Recent advances in the management of polycystic ovary syndrome: A review article. Cureus 2022 14 8 e27689 10.7759/cureus.27689 36072214
    [Google Scholar]
  4. Stańczak, N.A.; Grywalska, E.; Dudzińska, E. The latest reports and treatment methods on polycystic ovary syndrome. Ann. Med. 2024 56 1 2357737 10.1080/07853890.2024.2357737 38965663
    [Google Scholar]
  5. Ajmal N. Khan S.Z. Shaikh R. Polycystic ovary syndrome (PCOS) and genetic predisposition: A review article. Eur. J. Obstet. Gynecol. Reprod. Biol. X 2019 3 100060 10.1016/j.eurox.2019.100060 31403134
    [Google Scholar]
  6. Hajam Y.A. Rather H.A. Neelam; Kumar, R.; Basheer, M.; Reshi, M.S. A review on critical appraisal and pathogenesis of polycystic ovarian syndrome. Endocrine and Metabolic Science 2024 14 100162 10.1016/j.endmts.2024.100162
    [Google Scholar]
  7. Chang K.J. Chen J.H. Chen K.H. The pathophysiological mechanism and clinical treatment of polycystic ovary syndrome: A molecular and cellular review of the literature. Int. J. Mol. Sci. 2024 25 16 9037 10.3390/ijms25169037 39201722
    [Google Scholar]
  8. Sagvekar P. Kumar P. Mangoli V. Desai S. Mukherjee S. DNA methylome profiling of granulosa cells reveals altered methylation in genes regulating vital ovarian functions in polycystic ovary syndrome. Clin. Epigenetics 2019 11 1 61 10.1186/s13148‑019‑0657‑6 30975191
    [Google Scholar]
  9. Sanchez-Garrido M.A. Tena-Sempere M. Metabolic dysfunction in polycystic ovary syndrome: Pathogenic role of androgen excess and potential therapeutic strategies. Mol. Metab. 2020 35 100937 10.1016/j.molmet.2020.01.001 32244180
    [Google Scholar]
  10. Matsuyama S. Whiteside S. Li S.Y. Implantation and decidualization in PCOS: Unraveling the complexities of pregnancy. Int. J. Mol. Sci. 2024 25 2 1203 10.3390/ijms25021203 38256276
    [Google Scholar]
  11. Wawrzkiewicz-Jałowiecka, A.; Kowalczyk, K.; Trybek, P.; Jarosz, T.; Radosz, P.; Setlak, M.; Madej, P. In search of new therapeutics—molecular aspects of the pcos pathophysiology: Genetics, hormones, metabolism and beyond. Int. J. Mol. Sci. 2020 21 19 7054 10.3390/ijms21197054 32992734
    [Google Scholar]
  12. Chaudhary H. Patel J. Jain N.K. Joshi R. The role of polymorphism in various potential genes on polycystic ovary syndrome susceptibility and pathogenesis. J. Ovarian Res. 2021 14 1 125 10.1186/s13048‑021‑00879‑w 34563259
    [Google Scholar]
  13. Siddiqui S. Mateen S. Ahmad R. Moin S. A brief insight into the etiology, genetics, and immunology of polycystic ovarian syndrome (PCOS). J. Assist. Reprod. Genet. 2022 39 11 2439 2473 10.1007/s10815‑022‑02625‑7 36190593
    [Google Scholar]
  14. Jung Y.W. Lee G.H. Han Y.J. Cha D.H. Insight into the pathogensis of polycystic ovarian syndrome. J. Genet. Med. 2020 17 1 1 10 10.5734/JGM.2020.17.1.1
    [Google Scholar]
  15. Xu N. Azziz R. Goodarzi M.O. Epigenetics in polycystic ovary syndrome: A pilot study of global DNA methylation. Fertil. Steril. 2010 94 2 781 783.e1 10.1016/j.fertnstert.2009.10.020 19939367
    [Google Scholar]
  16. Xia Y. Che Y. Zhang X. Zhang C. Cao Y. Wang W. Xu P. Wu X. Yi L. Gao Q. Wang Y. Polymorphic CAG repeat in the androgen receptor gene in polycystic ovary syndrome patients. Mol. Med. Rep. 2012 5 5 1330 1334 22344533
    [Google Scholar]
  17. Eiras M.C. Pinheiro D.P. Romcy K.A.M. Ferriani R.A. Reis R.M.D. Furtado C.L.M. Polycystic ovary syndrome: The epigenetics behind the disease. Reprod. Sci. 2022 29 3 680 694 10.1007/s43032‑021‑00516‑3 33826098
    [Google Scholar]
  18. Mimouni N.E.H. Paiva I. Barbotin A.L. Timzoura F.E. Plassard D. Le Gras S. Ternier G. Pigny P. Catteau-Jonard S. Simon V. Prevot V. Boutillier A.L. Giacobini P. Polycystic ovary syndrome is transmitted via a transgenerational epigenetic process. Cell Metab. 2021 33 3 513 530.e8 10.1016/j.cmet.2021.01.004 33539777
    [Google Scholar]
  19. Szukiewicz D. Trojanowski S. Kociszewska A. Szewczyk G. Modulation of the Inflammatory Response in Polycystic Ovary Syndrome (PCOS)—Searching for Epigenetic Factors. Int. J. Mol. Sci. 2022 23 23 14663 10.3390/ijms232314663 36498989
    [Google Scholar]
  20. Sagvekar P. Shinde G. Mangoli V. Desai S.K. Mukherjee S. Evidence for TET-mediated DNA demethylation as an epigenetic alteration in cumulus granulosa cells of women with polycystic ovary syndrome. Mol. Hum. Reprod. 2022 28 7 gaac019 10.1093/molehr/gaac019 35640568
    [Google Scholar]
  21. Zhao H. Zhao Y. Ren Y. Li M. Li T. Li R. Yu Y. Qiao J. Epigenetic regulation of an adverse metabolic phenotype in polycystic ovary syndrome: The impact of the leukocyte methylation of PPARGC1A promoter. Fertil. Steril. 2017 107 2 467 474.e5 10.1016/j.fertnstert.2016.10.039 27889100
    [Google Scholar]
  22. Siemers K.M. Klein A.K. Baack M.L. Mitochondrial Dysfunction in PCOS: Insights into Reproductive Organ Pathophysiology. Int. J. Mol. Sci. 2023 24 17 13123 10.3390/ijms241713123 37685928
    [Google Scholar]
  23. Malamouli M. Levinger I. McAinch A.J. Trewin A.J. Rodgers R.J. Moreno-Asso A. The mitochondrial profile in women with polycystic ovary syndrome: Impact of exercise. J. Mol. Endocrinol. 2022 68 3 R11 R23 10.1530/JME‑21‑0177 35060480
    [Google Scholar]
  24. Mutharasan P. Galdones E. Peñalver Bernabé B. Garcia O.A. Jafari N. Shea L.D. Woodruff T.K. Legro R.S. Dunaif A. Urbanek M. Evidence for chromosome 2p16.3 polycystic ovary syndrome susceptibility locus in affected women of European ancestry. J. Clin. Endocrinol. Metab. 2013 98 1 E185 E190 10.1210/jc.2012‑2471 23118426
    [Google Scholar]
  25. Mao Z. Li T. Zhao H. Wang X. Kang Y. Kang Y. Methylome and transcriptome profiling revealed epigenetic silencing of LPCAT1 and PCYT1A associated with lipidome alterations in polycystic ovary syndrome. J. Cell. Physiol. 2021 236 9 6362 6375 10.1002/jcp.30309 33521992
    [Google Scholar]
  26. Salinas I. Sinha N. Sen A. Androgen-induced epigenetic modulations in the ovary. J. Endocrinol. 2021 249 3 R53 R64 10.1530/JOE‑20‑0578 33764313
    [Google Scholar]
  27. Liu Y.N. Qin Y. Wu B. Peng H. Li M. Luo H. Liu L.L. DNA methylation in polycystic ovary syndrome: Emerging evidence and challenges. Reprod. Toxicol. 2022 111 11 19 10.1016/j.reprotox.2022.04.010 35562068
    [Google Scholar]
  28. Vitti M. Di Emidio G. Di Carlo M. Carta G. Antonosante A. Artini P.G. Cimini A. Tatone C. Benedetti E. Peroxisome proliferator-activated receptors in female reproduction and fertility. PPAR Res. 2016 2016 1 12 10.1155/2016/4612306 27559343
    [Google Scholar]
  29. Shiue Y.L. Chen L.R. Tsai C.J. Yeh C.Y. Huang C.T. Emerging roles of peroxisome proliferator-activated receptors in the pituitary gland in female reproduction. Biomarker Genomic Med. 2013 5 1-2 1 11 10.1016/j.gmbhs.2013.04.008
    [Google Scholar]
  30. Psilopatis I. Theocharis S. Beckmann M.W. The role of peroxisome proliferator-activated receptors in endometriosis. Front. Med. (Lausanne) 2024 11 1329406 10.3389/fmed.2024.1329406 38690174
    [Google Scholar]
  31. Zhao H. Zhang J. Cheng X. Nie X. He B. Insulin resistance in polycystic ovary syndrome across various tissues: an updated review of pathogenesis, evaluation, and treatment. J. Ovarian Res. 2023 16 1 9 10.1186/s13048‑022‑01091‑0 36631836
    [Google Scholar]
  32. Shen H. Qiu L. Zhang Z. Qin Y. Cao C. Di W. Genome-wide methylated DNA immunoprecipitation analysis of patients with polycystic ovary syndrome. PLoS One 2013 8 5 e64801 10.1371/journal.pone.0064801 23705014
    [Google Scholar]
  33. Sadeghi H.M. Adeli I. Calina D. Docea A.O. Mousavi T. Daniali M. Nikfar S. Tsatsakis A. Abdollahi M. Polycystic ovary syndrome: A comprehensive review of pathogenesis, management, and drug repurposing. Int. J. Mol. Sci. 2022 23 2 583 10.3390/ijms23020583 35054768
    [Google Scholar]
  34. Zhang J. Bao Y. Zhou X. Zheng L. Polycystic ovary syndrome and mitochondrial dysfunction. Reprod. Biol. Endocrinol. 2019 17 1 67 10.1186/s12958‑019‑0509‑4 31420039
    [Google Scholar]
  35. Rajagopalan K.S. Kazeminia S. Glasstetter L.M. Farahani R.A. Zhu X.Y. Tang H. Jordan K.L. Chade A.R. Lerman A. Lerman L.O. Eirin A. Metabolic syndrome induces epigenetic alterations in mitochondria-related genes in swine mesenchymal stem cells. Cells 2023 12 9 1274 10.3390/cells12091274 37174674
    [Google Scholar]
  36. Mao Z. Li T. Zhao H. Qin Y. Wang X. Kang Y. Identification of epigenetic interactions between microRNA and DNA methylation associated with polycystic ovarian syndrome. J. Hum. Genet. 2021 66 2 123 137 10.1038/s10038‑020‑0819‑6 32759991
    [Google Scholar]
  37. Piya S. Lopes-Caitar V.S. Kim W.S. Pantalone V. Krishnan H.B. Hewezi T. Title: Hypermethylation of miRNA Genes During Nodule Development. Front. Mol. Biosci. 2021 8 616623 10.3389/fmolb.2021.616623 33928115
    [Google Scholar]
  38. Wang S. Wu W. Claret F.X. Mutual regulation of microRNAs and DNA methylation in human cancers. Epigenetics 2017 12 3 187 197 10.1080/15592294.2016.1273308 28059592
    [Google Scholar]
  39. Chen B. Xu P. Wang J. Zhang C. The role of MiRNA in polycystic ovary syndrome (PCOS). Gene 2019 706 91 96 10.1016/j.gene.2019.04.082 31054362
    [Google Scholar]
  40. Wolugbom J.A. Areloegbe S.E. Olaniyi K.S. Protective Role of Acetate Against Depressive-Like Behaviour Associated with Letrozole-Induced PCOS Rat Model: Involvement of HDAC2 and DNA Methylation. Mol. Neurobiol. 2023 60 1 355 368 10.1007/s12035‑022‑03074‑0 36269541
    [Google Scholar]
  41. Guo X. Puttabyatappa M. Thompson R.C. Padmanabhan V. Developmental programming: Contribution of Epigenetic enzymes to antral follicular defects in the sheep model of PCOS. Endocrinology 2019 160 10 2471 2484 10.1210/en.2019‑00389 31398247
    [Google Scholar]
  42. Hosseini E. Shahhoseini M. Afsharian P. Karimian L. Ashrafi M. Mehraein F. Afatoonian R. Role of epigenetic modifications in the aberrant CYP19A1 gene expression in polycystic ovary syndrome. Arch. Med. Sci. 2019 15 4 887 895 10.5114/aoms.2019.86060 31360184
    [Google Scholar]
  43. Eini F. Novin M.G. Joharchi K. Hosseini A. Nazarian H. Piryaei A. Bidadkosh A. Intracytoplasmic oxidative stress reverses epigenetic modifications in polycystic ovary syndrome. Reprod. Fertil. Dev. 2017 29 12 2313 2323 10.1071/RD16428 28442024
    [Google Scholar]
  44. Sandhu J.K. Waqar A. Jain A. Joseph C. Srivastava K. Ochuba O. Alkayyali T. Ruo S.W. Poudel S. Oxidative Stress in polycystic ovarian syndrome and the effect of antioxidant N-acetylcysteine on ovulation and pregnancy rate. Cureus 2021 13 9 e17887 10.7759/cureus.17887 34660086
    [Google Scholar]
  45. Sulaiman M. Al-Farsi Y. Al-Khaduri M. Saleh J. Waly M. Polycystic ovarian syndrome is linked to increased oxidative stress in Omani women. Int. J. Womens Health 2018 10 763 771 10.2147/IJWH.S166461 30568513
    [Google Scholar]
  46. Jia L. Li J. He B. Jia Y. Niu Y. Wang C. Zhao R. Abnormally activated one-carbon metabolic pathway is associated with mtDNA hypermethylation and mitochondrial malfunction in the oocytes of polycystic gilt ovaries. Sci. Rep. 2016 6 1 19436 10.1038/srep19436 26758245
    [Google Scholar]
  47. Viet Linh N. Kikuchi K. Nakai M. Tanihara F. Noguchi J. Kaneko H. Dang-Nguyen T.Q. Men N.T. Van Hanh N. Somfai T. Nguyen B.X. Nagai T. Manabe N. Fertilization ability of porcine oocytes reconstructed from ooplasmic fragments produced and characterized after serial centrifugations. J. Reprod. Dev. 2013 59 6 549 556 10.1262/jrd.2013‑042 23965685
    [Google Scholar]
  48. Halling J.F. Pilegaard H. PGC-1α-mediated regulation of mitochondrial function and physiological implications. Appl. Physiol. Nutr. Metab. 2020 45 9 927 936 10.1139/apnm‑2020‑0005 32516539
    [Google Scholar]
  49. Mthembu S.X.H. Mazibuko-Mbeje S.E. Ziqubu K. Muvhulawa N. Marcheggiani F. Cirilli I. Nkambule B.B. Muller C.J.F. Basson A.K. Tiano L. Dludla P.V. Potential regulatory role of PGC-1α within the skeletal muscle during metabolic adaptations in response to high-fat diet feeding in animal models. Pflugers Arch. 2024 476 3 283 293 10.1007/s00424‑023‑02890‑0 38044359
    [Google Scholar]
  50. Souza-Tavares H. Miranda C.S. Vasques-Monteiro I.M.L. Sandoval C. Santana-Oliveira D.A. Silva-Veiga F.M. Fernandes-da-Silva A. Souza-Mello V. Peroxisome proliferator-activated receptors as targets to treat metabolic diseases: Focus on the adipose tissue, liver, and pancreas. World J. Gastroenterol. 2023 29 26 4136 4155 10.3748/wjg.v29.i26.4136 37475842
    [Google Scholar]
  51. Reddy T.V. Govatati S. Deenadayal M. Shivaji S. Bhanoori M. Polymorphisms in the TFAM and PGC1-α genes and their association with polycystic ovary syndrome among South Indian women. Gene 2018 641 129 136 10.1016/j.gene.2017.10.010 29030253
    [Google Scholar]
  52. Chen Y. Xing L. Investigating the role of mitochondrial DNA D-loop variants, haplotypes, and copy number in polycystic ovary syndrome: Implications for clinical phenotypes in the Chinese population. Front. Endocrinol. (Lausanne) 2023 14
    [Google Scholar]
  53. Lee S.H. Chung D.J. Lee H.S. Kim T.J. Kim M.H. Jeong H.J. Im, J.A.; Lee, D.C.; Lee, J.W. Mitochondrial DNA copy number in peripheral blood in polycystic ovary syndrome. Metabolism 2011 60 12 1677 1682 10.1016/j.metabol.2011.04.010 21676419
    [Google Scholar]
  54. Yang P.K. Chou C.H. Chang C.H. Chen S.U. Ho H.N. Chen M.J. Changes in peripheral mitochondrial DNA copy number in metformin-treated women with polycystic ovary syndrome: A longitudinal study. Reprod. Biol. Endocrinol. 2020 18 1 69 10.1186/s12958‑020‑00629‑5 32660613
    [Google Scholar]
  55. Zhang Q. Ren J. Wang F. Pan M. Cui L. Li M. Qu F. Mitochondrial and glucose metabolic dysfunctions in granulosa cells induce impaired oocytes of polycystic ovary syndrome through Sirtuin 3. Free Radic. Biol. Med. 2022 187 1 16 10.1016/j.freeradbiomed.2022.05.010 35594990
    [Google Scholar]
  56. Cavalcante G.C. Magalhães L. Ribeiro-dos-Santos Â. Vidal A.F. Mitochondrial epigenetics: Non-coding RNAs as a Novel layer of complexity. Int. J. Mol. Sci. 2020 21 5 1838 10.3390/ijms21051838 32155913
    [Google Scholar]
  57. Devall M. Burrage J. Caswell R. Johnson M. Troakes C. Al-Sarraj S. Jeffries A.R. Mill J. Lunnon K. A comparison of mitochondrial DNA isolation methods in frozen post-mortem human brain tissue--applications for studies of mitochondrial genetics in brain disorders. Biotechniques 201559 4 241-246, 244-246. 10.2144/000114343 26458552
    [Google Scholar]
  58. Valdés-Aguayo J.J. Garza-Veloz I. Vargas-Rodríguez J.R. Martinez-Vazquez M.C. Avila-Carrasco L. Bernal-Silva S. González-Fuentes C. Comas-García A. Alvarado-Hernández D.E. Centeno-Ramirez A.S.H. Rodriguez-Sánchez I.P. Delgado-Enciso I. Martinez-Fierro M.L. Peripheral blood mitochondrial DNA levels were modulated by SARS-CoV-2 infection severity and its lessening was associated with mortality among hospitalized patients with COVID-19. Front. Cell. Infect. Microbiol. 2021 11 754708 10.3389/fcimb.2021.754708 34976854
    [Google Scholar]
  59. Ducreux B. Patrat C. Trasler J. Fauque P. Transcriptomic integrity of human oocytes used in ARTs: Technical and intrinsic factor effects. Hum. Reprod. Update 2023 37697674
    [Google Scholar]
  60. Ben Maamar M. Sadler-Riggleman I. Beck D. Skinner M.K. Genome-wide mapping of DNA methylation 5mC by methylated DNA immunoprecipitation (MeDIP)-sequencing. Methods Mol. Biol. 2021 2198 301 10.1007/978‑1‑0716‑0876‑0_23
    [Google Scholar]
  61. Cao P. Yang W. Wang P. Li X. Nashun B. Characterization of DNA Methylation and Screening of Epigenetic Markers in Polycystic Ovary Syndrome. Front. Cell Dev. Biol. 2021 9 664843 10.3389/fcell.2021.664843 34113617
    [Google Scholar]
  62. Tong H. Zhang L. Gao J. Wen S. Zhou H. Feng S. Methylation of mitochondrial DNA displacement loop region regulates mitochondrial copy number in colorectal cancer. Mol. Med. Rep. 2017 16 4 5347 5353 10.3892/mmr.2017.7264 28849075
    [Google Scholar]
  63. So M.Y. Tian Z. Phoon Y.S. Sha S. Antoniou M.N. Zhang J. Wu R.S.S. Tan-Un K.C. Gene expression profile and toxic effects in human bronchial epithelial cells exposed to zearalenone. PLoS One 2014 9 5 e96404 10.1371/journal.pone.0096404 24788721
    [Google Scholar]
  64. Celik Uzuner S. Mitochondrial DNA methylation misleads global DNA methylation detected by antibody-based methods. Anal. Biochem. 2020 601 113789 10.1016/j.ab.2020.113789 32473121
    [Google Scholar]
  65. Wong M. Gertz B. Chestnut B.A. Martin L.J. Mitochondrial DNMT3A and DNA methylation in skeletal muscle and CNS of transgenic mouse models of ALS. Front. Cell. Neurosci. 2013 7 279 10.3389/fncel.2013.00279 24399935
    [Google Scholar]
  66. Li J. Chen H. Gou M. Tian C. Wang H. Song X. Keefe D.L. Bai X. Liu L. Molecular features of polycystic ovary syndrome revealed by transcriptome analysis of oocytes and cumulus cells. Front. Cell Dev. Biol. 2021 9 735684 10.3389/fcell.2021.735684 34552933
    [Google Scholar]
  67. Zhong X. Jin F. Huang C. Du M. Gao M. Wei X. DNA methylation of AMHRII and INSR gene is associated with the pathogenesis of Polycystic Ovary Syndrome (PCOS). Technol. Health Care 2021 29 S1 11 25 10.3233/THC‑218002 33682741
    [Google Scholar]
  68. Arzenani M.K. Zade A.E. Ming Y. Vijverberg S.J.H. Zhang Z. Khan Z. Sadique S. Kallenbach L. Hu L. Vukojevi V.; Ekström, T.J. Genomic DNA hypomethylation by histone deacetylase inhibition implicates DNMT1 nuclear dynamics. Mol. Cell. Biol. 2011 31 19 4119 4128 10.1128/MCB.01304‑10 21791605
    [Google Scholar]
  69. Mechta M. Ingerslev L.R. Barrès R. Methodology for accurate detection of mitochondrial DNA methylation. J. Vis. Exp. 2018 20 135
    [Google Scholar]
  70. Liu B. Du Q. Chen L. Fu G. Li S. Fu L. Zhang X. Ma C. Bin C. CpG methylation patterns of human mitochondrial DNA. Sci. Rep. 2016 6 1 23421 10.1038/srep23421 26996456
    [Google Scholar]
  71. Gao C. Zhang Q. Kong D. Wu D. Su C. Tong J. Chen F. Zhang Q. MALDI-TOF mass array analysis of Nell-1 Promoter methylation patterns in human gastric cancer. BioMed Res. Int. 2015 2015 1 8 10.1155/2015/136941 26090379
    [Google Scholar]
  72. Li X. Franke A.A. High-throughput and cost-effective global DNA methylation assay by liquid chromatography-mass spectrometry. Anal. Chim. Acta 2011 703 1 58 63 10.1016/j.aca.2011.07.014 21843675
    [Google Scholar]
  73. Boulias K. Greer E.L. Detection of DNA methylation in genomic DNA by UHPLC-MS/MS. Methods Mol. Biol. 2021 2198 79 90 10.1007/978‑1‑0716‑0876‑0_7
    [Google Scholar]
  74. Rauschert S. Raubenheimer K. Melton P.E. Huang R.C. Machine learning and clinical epigenetics: A review of challenges for diagnosis and classification. Clin. Epigenetics 2020 12 1 51 10.1186/s13148‑020‑00842‑4 32245523
    [Google Scholar]
  75. Fahs D. Salloum D. Nasrallah M. Ghazeeri G. Polycystic ovary syndrome: Pathophysiology and controversies in diagnosis. Diagnostics 2023 13 9 1559 10.3390/diagnostics13091559 37174950
    [Google Scholar]
  76. Holder L.B. Haque M.M. Skinner M.K. Machine learning for epigenetics and future medical applications. Epigenetics 2017 12 7 505 514 10.1080/15592294.2017.1329068 28524769
    [Google Scholar]
  77. Zad Z. Jiang V.S. Wolf A.T. Wang T. Cheng J.J. Paschalidis I.C. Mahalingaiah S. Predicting polycystic ovary syndrome with machine learning algorithms from electronic health records. Front. Endocrinol. (Lausanne) 2024 15 1298628 10.3389/fendo.2024.1298628 38356959
    [Google Scholar]
  78. Tiwari S. Kane L. Koundal D. Jain A. Alhudhaif A. Polat K. Zaguia A. Alenezi F. Althubiti S.A. SPOSDS: A smart polycystic ovary syndrome diagnostic system using machine learning. Expert Syst. Appl. 2022 203 117592 10.1016/j.eswa.2022.117592
    [Google Scholar]
  79. Bachelot G. Bachelot A. Bonnier M. Salem J.E. Farabos D. Trabado S. Dupont C. Kamenicky P. Houang M. Fiet J. Le Bouc Y. Young J. Lamazière A. Combining metabolomics and machine learning models as a tool to distinguish non-classic 21-hydroxylase deficiency from polycystic ovary syndrome without adrenocorticotropic hormone testing. Hum. Reprod. 2023 38 2 266 276 10.1093/humrep/deac254 36427016
    [Google Scholar]
  80. Haque M.M. Holder L.B. Skinner M.K. Genome-Wide locations of potential epimutations associated with environmentally induced epigenetic transgenerational inheritance of disease using a sequential machine learning prediction approach. PLoS One 2015 10 11 e0142274 10.1371/journal.pone.0142274 26571271
    [Google Scholar]
  81. Oh G. Wang S.C. Pal M. Chen Z.F. Khare T. Tochigi M. Ng C. Yang Y.A. Kwan A. Kaminsky Z.A. Mill J. Gunasinghe C. Tackett J.L. Gottesman I.I. Willemsen G. de Geus E.J.C. Vink J.M. Slagboom P.E. Wray N.R. Heath A.C. Montgomery G.W. Turecki G. Martin N.G. Boomsma D.I. McGuffin P. Kustra R. Petronis A. DNA modification study of major depressive disorder: beyond locus-by-locus comparisons. Biol. Psychiatry 2015 77 3 246 255 10.1016/j.biopsych.2014.06.016 25108803
    [Google Scholar]
  82. Huang Y. Sun X. Jiang H. Yu S. Robins C. Armstrong M.J. Li R. Mei Z. Shi X. Gerasimov E.S. De Jager P.L. Bennett D.A. Wingo A.P. Jin P. Wingo T.S. Qin Z.S. A machine learning approach to brain epigenetic analysis reveals kinases associated with Alzheimer’s disease. Nat. Commun. 2021 12 1 4472 10.1038/s41467‑021‑24710‑8 34294691
    [Google Scholar]
/content/journals/cg/10.2174/0113892029401274251009070350
Loading
/content/journals/cg/10.2174/0113892029401274251009070350
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test