DNA methylation-based forensic age prediction using artificial neural networks and next generation sequencing

Highlights • Blood DNA methylation profiles of 1156 individuals were assessed for age correlation.• Stepwise regression identified 23 age-associated CpG sites in DNA from blood.• A machine learning model based on 16 markers predicted age with a mean error of 3.8 years.• The model predicted age successfully for twins and ‘diseased’ individuals.• A new NGS-based method was combined with machine learning for age prediction.

[1]  Fan Liu,et al.  CollapsABEL: an R library for detecting compound heterozygote alleles in genome-wide association studies , 2016, BMC Bioinformatics.

[2]  S. Horvath,et al.  Aging effects on DNA methylation modules in human brain and blood tissue , 2012, Genome Biology.

[3]  S. Horvath.  DNA methylation age of human tissues and cell types , 2013, Genome Biology.

[4]  S. Ritz‐Timme,et al.  Molecular pathology and age estimation. , 2010, Forensic science international.

[5]  Wilfred F J van IJcken,et al.  Human age estimation from blood using mRNA, DNA methylation, DNA rearrangement, and telomere length. , 2016, Forensic science international. Genetics.

[6]  Mahmood Amiri,et al.  Applied Artificial Neural Networks: from Associative Memories to Biomedical Applications , 2011 .

[7]  G. G. Stokes.  "J." , 1890, The New Yale Book of Quotations.

[8]  Andrew E. Teschendorff,et al.  Age-associated epigenetic drift: implications, and a case of epigenetic thrift? , 2013, Human molecular genetics.

[9]  K. Reed,et al.  Comparison of bisulfite sequencing PCR with pyrosequencing for measuring differences in DNA methylation. , 2010, Analytical biochemistry.

[10]  S. Mooney,et al.  Genome-wide DNA methylation changes with age in disease-free human skeletal muscle , 2013, Aging cell.

[11]  T. Huang,et al.  Functional characterization of Trip10 in cancer cell growth and survival , 2011, Journal of Biomedical Science.

[12]  L. Gordon,et al.  Longitudinal, genome-scale analysis of DNA methylation in twins from birth to 18 months of age reveals rapid epigenetic change in early life and pair-specific effects of discordance , 2013, Genome Biology.

[13]  R. Timkovich,et al.  His86 from the N-terminus of frataxin coordinates iron and is required for Fe-S cluster synthesis. , 2013, Biochemistry.

[14]  R. Płoski,et al.  Examination of DNA methylation status of the ELOVL2 marker may be useful for human age prediction in forensic science. , 2015, Forensic Science International: Genetics.

[15]  V. Calhoun,et al.  A Study of the Influence of Sex on Genome Wide Methylation , 2010, PloS one.

[16]  Rebecca Hardy,et al.  A BRCA1-mutation associated DNA methylation signature in blood cells predicts sporadic breast cancer incidence and survival , 2014, Genome Medicine.

[17]  Tom R. Gaunt,et al.  Systematic identification of genetic influences on methylation across the human life course , 2016, Genome Biology.

[18]  Lan Hu,et al.  A novel strategy for forensic age prediction by DNA methylation and support vector regression model , 2015, Scientific Reports.

[19]  Focused, high accuracy 5-methylcytosine quantitation with base resolution by benchtop next-generation sequencing , 2013, Epigenetics & Chromatin.

[20]  M. Ouchida,et al.  Inhibition of apoptosis by normal and aberrant Fli-1 and erg proteins involved in human solid tumors and leukemias , 1997, Oncogene.

[21]  Stephan Beck,et al.  Genome-wide DNA methylation analysis for diabetic nephropathy in type 1 diabetes mellitus , 2010, BMC Medical Genomics.

[22]  D. Boomsma,et al.  Epigenome-Wide Association Study of Wellbeing , 2015, Twin Research and Human Genetics.

[23]  A. Tsuji,et al.  Estimating age of humans based on telomere shortening. , 2002, Forensic science international.

[24]  Daixin Huang,et al.  Age-related DNA methylation changes for forensic age-prediction , 2015, International Journal of Legal Medicine.

[25]  T. Marquès-Bonet,et al.  DNA methylation contributes to natural human variation , 2013, Genome research.

[26]  T. Ideker,et al.  Genome-wide methylation profiles reveal quantitative views of human aging rates. , 2013, Molecular cell.

[27]  M. DePristo,et al.  The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. , 2010, Genome research.

[28]  D. Reinberg,et al.  Interaction of FACT, SSRP1, and the High Mobility Group (HMG) Domain of SSRP1 with DNA Damaged by the Anticancer Drug Cisplatin* , 2001, The Journal of Biological Chemistry.

[29]  István Simon,et al.  BiSearch: primer-design and search tool for PCR on bisulfite-treated genomes , 2005, Nucleic acids research.

[30]  V. Bencko,et al.  Changes in colour of different human tissues as a marker of age , 2007, International Journal of Legal Medicine.

[31]  Á. Carracedo,et al.  Development of a methylation marker set for forensic age estimation using analysis of public methylation data and the Agena Bioscience EpiTYPER system. , 2016, Forensic science international. Genetics.

[32]  Raimund Erbel,et al.  Aging of blood can be tracked by DNA methylation changes at just three CpG sites , 2014, Genome Biology.

[33]  D. Mari,et al.  Role of epigenetics in human aging and longevity: genome-wide DNA methylation profile in centenarians and centenarians’ offspring , 2012, AGE.

[34]  R. Sinha,et al.  Body Mass Index and Diabetes in Asia: A Cross-Sectional Pooled Analysis of 900,000 Individuals in the Asia Cohort Consortium , 2011, PloS one.

[35]  Steve Horvath,et al.  Epigenetic Predictor of Age , 2011, PloS one.

[36]  Jong-Lyul Park,et al.  Identification and evaluation of age-correlated DNA methylation markers for forensic use. , 2016, Forensic science international. Genetics.

[37]  K. Tamaki,et al.  Forensic age prediction for dead or living samples by use of methylation-sensitive high resolution melting. , 2016, Legal medicine.

[38]  Jiayi Hou,et al.  Developing a DNA methylation assay for human age prediction in blood and bloodstain. , 2015, Forensic science international. Genetics.

[39]  B. Korn,et al.  Aging and Chronic Sun Exposure Cause Distinct Epigenetic Changes in Human Skin , 2010, PLoS genetics.

[40]  Zdenka Pausova,et al.  Cigarette smoking and DNA methylation , 2013, Front. Genet..

[41]  Scott F. Heron,et al.  Caribbean Corals in Crisis: Record Thermal Stress, Bleaching, and Mortality in 2005 , 2010, PloS one.

[42]  Leopold Parts,et al.  Gene expression changes with age in skin, adipose tissue, blood and brain , 2013, Genome Biology.

[43]  J. Cigudosa,et al.  Aberrant DNA methylation profile of chronic and transformed classic Philadelphia-negative myeloproliferative neoplasms , 2013, Haematologica.

[44]  Richard Durbin,et al.  Sequence analysis Fast and accurate short read alignment with Burrows – Wheeler transform , 2009 .

[45]  R. Płoski,et al.  Development of a forensically useful age prediction method based on DNA methylation analysis. , 2015, Forensic science international. Genetics.

[46]  Mark I. McCarthy,et al.  Identification of an imprinted master trans-regulator at the KLF14 locus related to multiple metabolic phenotypes , 2011, Nature Genetics.

[47]  D. Slamon,et al.  Identification of differentially expressed genes associated with HER-2/neu overexpression in human breast cancer cells. , 1999, Nucleic acids research.

[48]  Wolfgang Wagner,et al.  Age-dependent DNA methylation of genes that are suppressed in stem cells is a hallmark of cancer. , 2010, Genome research.

[49]  B. Pickard,et al.  The EpiTect Methyl qPCR Assay as novel age estimation method in forensic biology. , 2016, Forensic science international.

[50]  Richard M Myers,et al.  Differential DNA methylation with age displays both common and dynamic features across human tissues that are influenced by CpG landscape , 2013, Genome Biology.

[51]  T. K. Harden,et al.  P2-purinergic receptors: subtype-associated signaling responses and structure. , 1995, Annual review of pharmacology and toxicology.

[52]  Chrysanthi Ainali,et al.  Differential methylation of the TRPA1 promoter in pain sensitivity , 2014, Nature Communications.

[53]  G. Horgan,et al.  Relative expression software tool (REST©) for group-wise comparison and statistical analysis of relative expression results in real-time PCR , 2002 .

[54]  D. Ubelaker,et al.  Applications of physiological bases of ageing to forensic sciences. Estimation of age-at-death , 2013, Ageing Research Reviews.

[55]  Yi-an Chen,et al.  Sequence overlap between autosomal and sex-linked probes on the Illumina HumanMethylation27 microarray. , 2011, Genomics.

[56]  Mihaela Zavolan,et al.  Insights into snoRNA biogenesis and processing from PAR-CLIP of snoRNA core proteins and small RNA sequencing , 2013, Genome Biology.

[57]  Owen T McCann,et al.  Human aging-associated DNA hypermethylation occurs preferentially at bivalent chromatin domains. , 2010, Genome research.

[58]  Gillian L McEneff,et al.  Gradient liquid chromatographic retention time prediction for suspect screening applications: A critical assessment of a generalised artificial neural network-based approach across 10 multi-residue reversed-phase analytical methods. , 2016, Talanta.

[59]  Michael J Leach,et al.  Longitudinal , 2015, The Medical journal of Australia.

[60]  G. Satten,et al.  Age-associated DNA methylation in pediatric populations. , 2012, Genome research.

[61]  D. Oxley,et al.  Disease Biomarkers in Cerebrospinal Fluid of Patients with First-Onset Psychosis , 2006, PLoS medicine.

[62]  Ronald W Davis,et al.  Multiplex Pyrosequencing. , 2002, Nucleic acids research.

[63]  R. Díaz,et al.  The role of nutrition on epigenetic modifications and their implications on health. , 2012, Biochimie.

[64]  Hu Zhao,et al.  Detection and quantification of the age-related sjTREC decline in human peripheral blood , 2011, International Journal of Legal Medicine.

[65]  Richard Durbin,et al.  Fast and accurate long-read alignment with Burrows–Wheeler transform , 2010, Bioinform..

[66]  M. Stöter,et al.  Interaction of casein kinase 1 delta (CK1delta) with post-Golgi structures, microtubules and the spindle apparatus. , 2000, European journal of cell biology.

[67]  M. Ronaghi.  Pyrosequencing sheds light on DNA sequencing. , 2001, Genome research.

[68]  W. Wagner,et al.  Epigenetic-aging-signature to determine age in different tissues , 2011, Aging.

[69]  Gonçalo R. Abecasis,et al.  The Sequence Alignment/Map format and SAMtools , 2009, Bioinform..

[70]  G. Castellani,et al.  Methylation of ELOVL2 gene as a new epigenetic marker of age , 2012, Aging cell.

[71]  R. Decorte,et al.  Improved age determination of blood and teeth samples using a selected set of DNA methylation markers , 2015, Epigenetics.

[72]  Robin M. Murray,et al.  Epigenome-Wide Scans Identify Differentially Methylated Regions for Age and Age-Related Phenotypes in a Healthy Ageing Population , 2012, PLoS genetics.

[73]  B. McCord,et al.  Evaluation of DNA methylation markers and their potential to predict human aging , 2015, Electrophoresis.

[74]  D. Hochstrasser,et al.  A panel of cerebrospinal fluid potential biomarkers for the diagnosis of Alzheimer's disease , 2003, Proteomics.

[75]  Daixin Huang,et al.  Isolation and identification of age-related DNA methylation markers for forensic age-prediction. , 2014, Forensic science international. Genetics.

[76]  H. Kitchener,et al.  The Dynamics and Prognostic Potential of DNA Methylation Changes at Stem Cell Gene Loci in Women's Cancer , 2012, PLoS genetics.