Longitudinal prediction of DNA methylation to forecast epigenetic outcomes (2312.13302v1)
Abstract: Interrogating the evolution of biological changes at early stages of life requires longitudinal profiling of molecules, such as DNA methylation, which can be challenging with children. We introduce a probabilistic and longitudinal machine learning framework based on multi-mean Gaussian processes (GPs), accounting for individual and gene correlations across time. This method provides future predictions of DNA methylation status at different individual ages while accounting for uncertainty. Our model is trained on a birth cohort of children with methylation profiled at ages 0-4, and we demonstrated that the status of methylation sites for each child can be accurately predicted at ages 5-7. We show that methylation profiles predicted by multi-mean GPs can be used to estimate other phenotypes, such as epigenetic age, and enable comparison to other health measures of interest. This approach encourages epigenetic studies to move towards longitudinal design for investigating epigenetic changes during development, ageing and disease progression.
- Modeling tumor evolutionary dynamics to predict clinical outcomes for patients with metastatic colorectal cancer: A retrospective analysis. Cancer Research, 80(3):591–601, 2020.
- The roles of dna methylation in the stages of cancer. Cancer Journal, 23(5):257–261, 2017.
- Potential utility of longitudinal somatic mutation and methylation profiling for predicting molecular residual disease in postoperative non-small cell lung cancer patients. Cancer Medicine, 10(23):8377–8386, 2021.
- Epigenetic regulation in cardiovascular disease: mechanisms and advances in clinical trials. Signal Transduction and Targeted Therapy, 7(1):200, 2022.
- Selecting a sample size for studies with repeated measures. BMC medical research methodology, 13(1):1–8, 2013.
- Steve Horvath. Dna methylation age of human tissues and cell types. Genome biology, 14(10):1–20, 2013.
- methylclock: a bioconductor package to estimate dna methylation age. Bioinformatics, 37(12):1759–1760, 2021.
- An epigenetic biomarker of aging for lifespan and healthspan. Aging (albany NY), 10(4):573, 2018.
- The pedbe clock accurately estimates dna methylation age in pediatric buccal cells. Proceedings of the National Academy of Sciences, 117(38):23329–23335, 2020.
- Peripheral blood dna methylation profiles are indicative of head and neck squamous cell carcinoma: an epigenome-wide association study. Epigenetics, 7(3):291–299, 2012.
- Dna methylation changes associated with type 2 diabetes and diabetic kidney disease in an east asian population. The Journal of Clinical Endocrinology & Metabolism, 106(10):e3837–e3851, 2021.
- Dna methylation signatures of depressive symptoms in middle-aged and elderly persons: meta-analysis of multiethnic epigenome-wide studies. JAMA psychiatry, 75(9):949–959, 2018.
- Epigenome-wide association study of depression symptomatology in elderly monozygotic twins. Transl Psychiatry, 9(1):214, 2019.
- Pretimeth: precise prediction models for dna methylation based on single methylation mark. BMC Genomics, 21(364), 2020.
- Predicting genome-wide dna methylation using methylation marks, genomic position, and dna regulatory elements. Genome Biology, 16(14), 2015.
- Cohort profile: Growing up in singapore towards healthy outcomes (gusto) birth cohort study. International journal of epidemiology, 43(5):1401–1409, 2014.
- Magma: inference and prediction using multi-task gaussian processes with common mean. Machine Learning, 111(5):1821–1849, 2022.
- Epigenetic clock for skin and blood cells applied to hutchinson gilford progeria syndrome and ex vivo studies. Aging (Albany NY), 10(7):1758, 2018.
- The pediatric buccal epigenetic clock identifies significant ageing acceleration in children with internalizing disorder and maltreatment exposure. Neurobiology of Stress, 15(100394), 2021.
- Determination of saliva epigenetic age in infancy, and its association with parental socio-economic characteristics and pregnancy outcomes. Journal of Developmental Origins of Health and Disease, 12(2):319–327, 2021.
- Physical activity is associated with slower epigenetic ageing—findings from the rhineland study. Aging Cell, page e13828, 2023.
- Obesity susceptible novel dna methylation marker on regulatory region of inflammation gene: results from the korea epigenome study (kes). BMJ Open Diabetes Res Care, 8(1):e001338, 2020.
- Novel associations between blood dna methylation and body mass index in middle-aged and older adults. Int J Obes (Lond), 42(4):887–896, 2018.
- Minfi: a flexible and comprehensive bioconductor package for the analysis of infinium dna methylation microarrays. Bioinformatics, 30(10):1363–9, 2014.
- MagmaClustR: Clustering and Prediction using Multi-Task Gaussian Processes with Common Mean, 2023. https://github.com/ArthurLeroy/MagmaClustR, https://arthurleroy.github.io/MagmaClustR/.
- RStudio Team. RStudio: Integrated Development Environment for R. RStudio, PBC., Boston, MA, 2020. URL http://www.rstudio.com/.