Small-Magnitude Effect Sizes in Epigenetic End Points are Important in Children’s Environmental Health Studies: The Children’s Environmental Health and Disease Prevention Research Center’s Epigenetics Working Group

• Carrie V. Breton ^[1] ; Carmen J. Marsit ^[2] ; Elaine Faustman ^[3] ; Kari Nadeau ^[9] ; Jaclyn M. Goodrich ^[4] ; Dana C. Dolinoy ^[4] ; Julie Herbstman ^[5] ; Nina Holland ^[10] ; Janine M. LaSalle ^[11] ; Rebecca Schmidt ^[11] ; Paul Yousefi ^[10] ; Frederica Perera ^[5] ; Bonnie R. Joubert ^[6] ; Joseph Wiemels ^[12] ; Michele Taylor ^[7] ; Ivana V. Yang ^[13] ; Rui Chen ^[8] ; Kinjal M. Hew ^[8] ; Deborah M. Hussey Freeland ^[8] ; Rachel Miller ^[5] ; Susan K. Murphy ^[7]
  1. [1] University of Southern California

     University of Southern California

     Estados Unidos

     
  2. [2] Emory University

     Emory University

     Estados Unidos

     
  3. [3] University of Washington

     University of Washington

     Estados Unidos

     
  4. [4] University of Michigan–Ann Arbor

     University of Michigan–Ann Arbor

     City of Ann Arbor, Estados Unidos

     
  5. [5] Columbia University

     Columbia University

     Estados Unidos

     
  6. [6] National Institute of Environmental Health Sciences

     National Institute of Environmental Health Sciences

     Township of Durham, Estados Unidos

     
  7. [7] Duke University

     Duke University

     Township of Durham, Estados Unidos

     
  8. [8] Stanford University

     Stanford University

     Estados Unidos

     
  9. [9] 4 Stanford University, Palo Alto, California, USA; 5 University of California, Berkeley, Berkeley, California, USA
  10. [10] 5 University of California, Berkeley, Berkeley, California, USA
  11. [11] 8 University of California, Davis, Davis, Califronia, USA
  12. [12] 10 University of California at San Francisco, San Francisco, California, USA
  13. [13] 12 University of Colorado, Denver, Colorado, USA; 13 National Jewish Health, Denver, Colorado, USA

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• Localización: Environmental health perspectives, ISSN 0091-6765, Vol. 125, Nº. 4, 2017, págs. 511-526
• Idioma: inglés
• DOI: 10.1289/EHP595
• Enlaces
  • Texto completo
• Resumen

  • Characterization of the epigenome is a primary interest for children’s environmental health researchers studying the environmental influences on human populations, particularly those studying the role of pregnancy and early-life exposures on later-in-life health outcomes.

    Our objective was to consider the state of the science in environmental epigenetics research and to focus on DNA methylation and the collective observations of many studies being conducted within the Children’s Environmental Health and Disease Prevention Research Centers, as they relate to the Developmental Origins of Health and Disease (DOHaD) hypothesis.

    We address the current laboratory and statistical tools available for epigenetic analyses, discuss methods for validation and interpretation of findings, particularly when magnitudes of effect are small, question the functional relevance of findings, and discuss the future for environmental epigenetics research.

    A common finding in environmental epigenetic studies is the small-magnitude epigenetic effect sizes that result from such exposures. Although it is reasonable and necessary that we question the relevance of such small effects, we present examples in which small effects persist and have been replicated across populations and across time. We encourage a critical discourse on the interpretation of such small changes and further research on their functional relevance for children’s health.

    The dynamic nature of the epigenome will require an emphasis on future longitudinal studies in which the epigenome is profiled over time, over changing environmental exposures, and over generations to better understand the multiple ways in which the epigenome may respond to environmental stimuli.

    Breton CV, Marsit CJ, Faustman E, Nadeau K, Goodrich JM, Dolinoy DC, Herbstman J, Holland N, LaSalle JM, Schmidt R, Yousefi P, Perera F, Joubert BR, Wiemels J, Taylor M, Yang IV, Chen R, Hew KM, Freeland DM, Miller R, Murphy SK. 2017. Small-magnitude effect sizes in epigenetic end points are important in children’s environmental health studies: the Children’s Environmental Health and Disease Prevention Research Center’s Epigenetics Working Group. Environ Health Perspect 125:–526; http://dx.doi.org/10.1289/EHP595

• Referencias bibliográficas
  • Aryee, MJ, Jaffe, AE, Corrada-Bravo, H, Ladd-Acosta, C, Feinberg, AP, Hansen, KD. (2014). Minfi: a flexible and comprehensive Bioconductor...
  • Baccarelli, A, Wright, RO, Bollati, V, Tarantini, L, Litonjua, AA, Suh, HH. (2009). Rapid DNA methylation changes after exposure to traffic...
  • Bakulski, KM, Feinberg, JI, Andrews, SV, Yang, J, Brown, S, McKenney, SL. (2016). DNA methylation of cord blood cell types: applications for...
  • Ball, MP, Li, JB, Gao, Y, Lee, JH, LeProust, EM, Park, IH. (2009). Targeted and genome-scale strategies reveal gene-body methylation signatures...
  • Barker, DJ. (1988). Childhood causes of adult diseases.. Arch Dis Child. 63. 867-869
  • Barker, DJ. (1995). Fetal origins of coronary heart disease.. BMJ. 311. 171-174
  • Barker, DJ, Osmond, C. (1988). Low birth weight and hypertension.. BMJ. 297. 134-135
  • Barker, DJ, Osmond, C, Law, CM. (1989). The intrauterine and early postnatal origins of cardiovascular disease and chronic bronchitis.. J...
  • Baron, RM, Kenny, DA. (1986). The moderator-mediator variable distinction in social psychological research: conceptual, strategic, and statistical...
  • Bellamy, GJ, Hinchliffe, RF, Crawshaw, KC, Finn, A, Bell, F. (2000). Total and differential leucocyte counts in infants at 2, 5 and 13 months...
  • Bernal, AJ, Jirtle, RL. (2010). Epigenomic disruption: the effects of early developmental exposures.. Birth Defects Res A Clin Mol Teratol....
  • Bock, C, Tomazou, EM, Brinkman, AB, Müller, F, Simmer, F, Gu, H. (2010). Quantitative comparison of genome-wide DNA methylation mapping technologies.....
  • Breiman, L. (2001). Random forests.. Mach Learn. 45. 5-32
  • Breton, CV, Byun, HM, Wenten, M, Pan, F, Yang, A, Gilliland, FD. (2009). Prenatal tobacco smoke exposure affects global and gene-specific...
  • Broberg, K, Ahmed, S, Engström, K, Hossain, MB, Jurkovic Mlakar, S, Bottai, M. (2014). Arsenic exposure in early pregnancy alters genome-wide...
  • Burris, HH, Braun, JM, Byun, HM, Tarantini, L, Mercado, A, Wright, RJ. (2013). Association between birth weight and DNA methylation of. Epigenomics....
  • Burris, HH, Rifas-Shiman, SL, Baccarelli, A, Tarantini, L, Boeke, CE, Kleinman, K. (2012). Associations of LINE-1 DNA methylation with preterm...
  • Butcher, LM, Beck, S. (2015). Probe Lasso: a novel method to rope in differentially methylated regions with 450K DNA methylation data.. Methods....
  • Cardenas, A, Koestler, DC, Houseman, EA, Jackson, BP, Kile, ML, Karagas, MR. (2015). Differential DNA methylation in umbilical cord blood...
  • Chambaz, A, Neuvial, P, van der Laan, MJ. (2011). Estimation of a non-parametric variable importance measure of a continuous exposure.. Electronic...
  • Chen, R, Mias, GI, Li-Pook-Than, J, Jiang, L, Lam, HY, Chen, R. (2012). Personal omics profiling reveals dynamic molecular and medical phenotypes.....
  • Chen, R, Snyder, M. (2013). Promise of personalized omics to precision medicine.. Wiley Interdiscip Rev Syst Biol Med. 5. 73-82
  • Chen, Y, Qiao, J. (2015). Protein-protein interaction network analysis and identifying regulation microRNAs in asthmatic children.. Allergol...
  • Cheng, CK, Chan, J, Cembrowski, GS, van Assendelft, OW. (2004). Complete blood count reference interval diagrams derived from NHANES III:...
  • Chipman, HA, George, EI, McCulloch, RE. (2010). BART: Bayesian additive regression trees.. Ann Appl Stat. 4. 266-298
  • Cho, YH, Yazici, H, Wu, HC, Terry, MB, Gonzalez, K, Qu, M. (2010). Aberrant promoter hypermethylation and genomic hypomethylation in tumor,...
  • Colquitt, BM, Allen, WE, Barnea, G, Lomvardas, S. (2013). Alteration of genic 5-hydroxymethylcytosine patterning in olfactory neurons correlates...
  • Cui, H, Cruz-Correa, M, Giardiello, FM, Hutcheon, DF, Kafonek, DR, Brandenburg, S. (2003). Loss of. Science. 299. 1753-1755
  • Davey Smith, G, Hemani, G. (2014). Mendelian randomization: genetic anchors for causal inference in epidemiological studies.. Hum Mol Genet....
  • Devaney, JM, Wang, S, Furbert-Harris, P, Apprey, V, Ittmann, M, Wang, BD. (2015). Genome-wide differentially methylated genes in prostate...
  • Dolinoy, DC, Das, R, Weidman, JR, Jirtle, RL. (2007). Metastable epialleles, imprinting, and the fetal origins of adult diseases.. Pediatr...
  • Finer, S, Mathews, C, Lowe, R, Smart, M, Hillman, S, Foo, L. (2015). Maternal gestational diabetes is associated with genome-wide DNA methylation...
  • Flanagan, JM, Brook, MN, Orr, N, Tomczyk, K, Coulson, P, Fletcher, O. (2015). Temporal stability and determinants of white blood cell DNA...
  • Friedman, JH. (1991). Multivariate adaptive regression splines.. Ann Stat. 19. 1-67
  • Fritz, MS, MacKinnon, DP. (2007). Required sample size to detect the mediated effect.. Psychol Sci. 18. 233-239
  • Génin, E, Devoto, M. (2015). Integration of omics data in genetic epidemiology.. Hum Hered. 79. 109-110
  • Gevaert, O. (2015). MethylMix: an R package for identifying DNA methylation-driven genes.. Bioinformatics. 31. 1839-1841
  • Goodrich, JM, Sanchez, BN, Dolinoy, DC, Zhang, Z, Hernández-Ávila, M, Hu, H. (2015). Quality control and statistical modeling for environmental...
  • Gruber, S, van der Laan, MJ. (2012). tmle: an R package for targeted maximum likelihood estimation.. J Stat Softw. 51. 1-35
  • Grunau, C, Schattevoy, R, Mache, N, Rosenthal, A. (2000). MethTools—a toolbox to visualize and analyze DNA methylation data.. Nucleic Acids...
  • Hahn, MA, Szabó, PE, Pfeifer, GP. (2014). 5-Hydroxymethylcytosine: a stable or transient DNA modification?. Genomics. 104. 314-323
  • Hales, CN, Barker, DJ, Clark, PM, Cox, LJ, Fall, C, Osmond, C. (1991). Fetal and infant growth and impaired glucose tolerance at age 64.....
  • Heijmans, BT, Tobi, EW, Stein, AD, Putter, H, Blauw, GJ, Susser, ES. (2008). Persistent epigenetic differences associated with prenatal exposure...
  • Hilton, IB, D’Ippolito, AM, Vockley, CM, Thakore, PI, Crawford, GE, Reddy, TE. (2015). Epigenome editing by a CRISPR-Cas9-based acetyltransferase...
  • Hou, L, Zhang, X, Zheng, Y, Wang, S, Dou, C, Guo, L. (2014). Altered methylation in tandem repeat element and elemental component levels in...
  • Houseman, EA, Molitor, J, Marsit, CJ. (2014). Reference-free cell mixture adjustments in analysis of DNA methylation data.. Bioinformatics....
  • Hoyo, C, Murtha, AP, Schildkraut, JM, Jirtle, RL, Demark-Wahnefried, W, Forman, MR. (2011). Methylation variation at. Epigenetics. 6. 928-936
  • Huen, K, Yousefi, P, Bradman, A, Yan, L, Harley, KG, Kogut, K. (2014). Effects of age, sex, and persistent organic pollutants on DNA methylation...
  • (2015). PON1 as a model for integration of genetic, epigenetic, and expression data on candidate susceptibility genes.. Environ Epigenet....
  • Irizarry, RA, Ladd-Acosta, C, Wen, B, Wu, Z, Montano, C, Onyango, P. (2009). The human colon cancer methylome shows similar hypo- and hypermethylation...
  • Issa, JP. (2014). Aging and epigenetic drift: a vicious cycle.. J Clin Invest. 124. 24-29
  • Jaffe, AE, Murakami, P, Lee, H, Leek, JT, Fallin, MD, Feinberg, AP. (2012). Bump hunting to identify differentially methylated regions in...
  • Janssen, BG, Byun, HM, Gyselaers, W, Lefebvre, W, Baccarelli, AA, Nawrot, TS. (2015). Placental mitochondrial methylation and exposure to...
  • Ji, H, Ehrlich, LI, Seita, J, Murakami, P, Doi, A, Lindau, P. (2010). Comprehensive methylome map of lineage commitment from haematopoietic...
  • Jirtle, RL. (2014). The Agouti mouse: a biosensor for environmental epigenomics studies investigating the developmental origins of health...
  • Johnson, WE, Li, C, Rabinovic, A. (2007). Adjusting batch effects in microarray expression data using empirical Bayes methods.. Biostatistics....
  • Joubert, BR, Felix, JF, Yousefi, P, Bakulski, KM, Just, AC, Breton, C. (2016). DNA methylation in newborns and maternal smoking in pregnancy:...
  • Kan, Q, Ding, S, Yang, Y, Zhou, X. (2015). Expression profile of plasma microRNAs in premature infants with respiratory distress syndrome.....
  • Kanzleiter, T, Jähnert, M, Schulze, G, Selbig, J, Hallahan, N, Schwenk, RW. (2015). Exercise training alters DNA methylation patterns in genes...
  • Kellis, M, Wold, B, Snyder, MP, Bernstein, BE, Kundaje, A, Marinov, GK. (2014). Defining functional DNA elements in the human genome.. Proc...
  • Kile, ML, Houseman, EA, Baccarelli, A, Quamruzzaman, Q, Rahman, M, Mostofa, G. (2014). Effect of prenatal arsenic exposure on DNA methylation...
  • Kippler, M, Engstrom, K, Mlakar, SJ, Bottai, M, Ahmed, S, Hossain, MB. (2013). Sex-specific effects of early life cadmium exposure on DNA...
  • Knopik, VS, Maccani, MA, Francazio, S, McGeary, JE. (2012). The epigenetics of maternal cigarette smoking during pregnancy and effects on...
  • (2016). Presence of an epigenetic signature of prenatal cigarette smoke exposure in childhood.. Environ Res. 144. 139-148
  • Laird, PW. (2010). Principles and challenges of genomewide DNA methylation analysis.. Nat Rev Genet. 11. 191-203
  • Lam, LL, Emberly, E, Fraser, HB, Neumann, SM, Chen, E, Miller, GE. (2012). Factors underlying variable DNA methylation in a human community...
  • LaRocca, J, Binder, AM, McElrath, TF, Michels, KB. (2014). The impact of first trimester phthalate and phenol exposure on. Environ Res. 133....
  • Lazarus, J, Mather, KA, Armstrong, NJ, Song, F, Poljak, A, Thalamuthu, A. (2015). DNA methylation in the apolipoprotein-A1 gene is associated...
  • Leek, JT, Johnson, WE, Parker, HS, Jaffe, AE, Storey, JD. (2012). The sva package for removing batch effects and other unwanted variation...
  • Leek, JT, Storey, JD. (2007). Capturing heterogeneity in gene expression studies by surrogate variable analysis.. PLoS Genet. 3. 1724-1735
  • Leek, JT, Storey, JD. (2008). A general framework for multiple testing dependence.. Proc Natl Acad Sci U S A. 105. 18718-18723
  • Lendle, SD, Subbaraman, MS, van der Laan, MJ. (2013). Identification and efficient estimation of the natural direct effect among the untreated.....
  • Leon, DA, Lithell, HO, Vâgerö, D, Koupilová, I, Mohsen, R, Berglund, L. (1998). Reduced fetal growth rate and increased risk of death from...
  • Li, JJ, Tay, HL, Maltby, S, Xiang, Y, Eyers, F, Hatchwell, L. (2015). MicroRNA-9 regulates steroid-resistant airway hyperresponsiveness by...
  • Li, Q, Kappil, MA, Li, A, Dassanayake, PS, Darrah, TH, Friedman, AE. (2015). Exploring the associations between microRNA expression profiles...
  • Li, SD. (2011). Testing mediation using multiple regression and structural equation modeling analyses in secondary data.. Eval Rev. 35. 240-268
  • Lian, CG, Xu, Y, Ceol, C, Wu, F, Larson, A, Dresser, K. (2012). Loss of 5-hydroxymethylcytosine is an epigenetic hallmark of melanoma.. Cell....
  • Liu, X, Chen, Q, Tsai, HJ, Wang, G, Hong, X, Zhou, Y. (2014). Maternal preconception body mass index and offspring cord blood DNA methylation:...
  • Lowe, R, Slodkowicz, G, Goldman, N, Rakyan, VK. (2015). The human blood DNA methylome displays a highly distinctive profile compared with...
  • Lu, TX, Munitz, A, Rothenberg, ME. (2009). MicroRNA-21 is up-regulated in allergic airway inflammation and regulates IL-12p35 expression.....
  • Maccani, JZ, Maccani, MA. (2015). Altered placental DNA methylation patterns associated with maternal smoking: current perspectives.. Adv...
  • Maeder, ML, Angstman, JF, Richardson, ME, Linder, SJ, Cascio, VM, Tsai, SQ. (2013). Targeted DNA demethylation and activation of endogenous...
  • Matsuda, Y, Yamashita, S, Lee, YC, Niwa, T, Yoshida, T, Gyobu, K. (2012). Hypomethylation of Alu repetitive elements in esophageal mucosa,...
  • Mattes, J, Collison, A, Plank, M, Phipps, S, Foster, PS. (2009). Antagonism of microRNA-126 suppresses the effector function of T. Proc Natl...
  • Michel, S, Busato, F, Genuneit, J, Pekkanen, J, Dalphin, JC, Riedler, J. (2013). Farm exposure and time trends in early childhood may influence...
  • Morales, E, Bustamante, M, Vilahur, N, Escaramis, G, Montfort, M, de Cid, R. (2012). DNA hypomethylation at. Am J Respir Crit Care Med. 185....
  • Moran, S, Arribas, C, Esteller, M. (2016). Validation of a DNA methylation microarray for 850,000 CpG sites of the human genome enriched in...
  • Morris, TJ, Beck, S. (2015). Analysis pipelines and packages for Infinium HumanMethylation450 BeadChip (450k) data.. Methods. 72. 3-8
  • Morris, TJ, Butcher, LM, Feber, A, Teschendorff, AE, Chakravarthy, AR, Wojdacz, TK. (2014). ChAMP: 450k Chip Analysis Methylation Pipeline.....
  • Murphy, SK, Adigun, A, Huang, Z, Overcash, F, Wang, F, Jirtle, RL. (2012). Gender-specific methylation differences in relation to prenatal...
  • Nahar, MS, Kim, JH, Sartor, MA, Dolinoy, DC. (2014). Bisphenol A-associated alterations in the expression and epigenetic regulation of genes...
  • (2013). Lower levels of hsa-mir-15a, which decreases. J Allergy Clin Immunol. 132. 1224-122712
  • Novakovic, B, Ryan, J, Pereira, N, Boughton, B, Craig, JM, Saffery, R. (2014). Postnatal stability, tissue, and time specific effects of AHRR...
  • Olden, K, Lin, YS, Gruber, D, Sonawane, B. (2014). Epigenome: biosensor of cumulative exposure to chemical and nonchemical stressors related...
  • Oliver, VF, Franchina, M, Jaffe, AE, Branham, KE, Othman, M, Heckenlively, JR. (2013). Hypomethylation of the. Cell Rep. 5. 1527-1535
  • Paquette, AG, Lester, BM, Lesseur, C, Armstrong, DA, Guerin, DJ, Appleton, AA. (2015). Placental epigenetic patterning of glucocorticoid response...
  • Pedersen, BS, Schwartz, DA, Yang, IV, Kechris, KJ. (2012). Comb-p: software for combining, analyzing, grouping and correcting spatially correlated....
  • Perry, MM, Adcock, IM, Chung, KF. (2015). Role of microRNAs in allergic asthma: present and future.. Curr Opin Allergy Clin Immunol. 15. 156-162
  • Petersen, M, Schwab, J, Gruber, S, Blaser, N, Schomaker, M, van der Laan, M. (2014). Targeted maximum likelihood estimation for dynamic and...
  • Petersen, ML, Sinisi, SE, van der Laan, MJ. (2006). Estimation of direct causal effects.. Epidemiology. 17. 276-284
  • Plongthongkum, N, Diep, DH, Zhang, K. (2014). Advances in the profiling of DNA modifications: cytosine methylation and beyond.. Nat Rev Genet....
  • Polikepahad, S, Knight, JM, Naghavi, AO, Oplt, T, Creighton, CJ, Shaw, C. (2010). Proinflammatory role for. J Biol Chem. 285. 30139-30149
  • Rao, SS, Huntley, MH, Durand, NC, Stamenova, EK, Bochkov, ID, Robinson, JT. (2014). A 3D map of the human genome at kilobase resolution reveals...
  • Relton, CL, Davey Smith, G. (2012). Two-step epigenetic Mendelian randomization: a strategy for establishing the causal role of epigenetic...
  • Relton, CL, Davey Smith, G. (2015). Mendelian randomization: applications and limitations in epigenetic studies.. Epigenomics. 7. 1239-1243
  • Richmond, RC, Sharp, GC, Ward, ME, Fraser, A, Lyttleton, O, McArdle, WL. (2016). DNA methylation and BMI: investigating identified methylation...
  • Richmond, RC, Simpkin, AJ, Woodward, G, Gaunt, TR, Lyttleton, O, McArdle, WL. (2015). Prenatal exposure to maternal smoking and offspring...
  • (2015). Integrative analysis of 111 reference human epigenomes.. Nature. 518. 317-330
  • Robertson, KD. (2005). DNA methylation and human disease.. Nat Rev Genet. 6. 597-610
  • Saha, R, Chowdhury, A, Maranas, CD. (2014). Recent advances in the reconstruction of metabolic models and integration of omics data.. Curr...
  • Salam, MT. (2014). Asthma epigenetics.. Adv Exp Med Biol. 795. 183-199
  • (2012). Genetic and epigenetic variations in inducible nitric oxide synthase promoter, particulate pollution, and exhaled nitric oxide levels...
  • Sawant, DV, Yao, W, Wright, Z, Sawyers, C, Tepper, RS, Gupta, SK. (2015). Serum microRNA-21 as a biomarker for allergic inflammatory disease...
  • Schones, DE, Leung, A, Natarajan, R. (2015). Chromatin modifications associated with diabetes and obesity.. Arterioscler Thromb Vasc Biol....
  • Schones, DE, Zhao, K. (2008). Genome-wide approaches to studying chromatin modifications.. Nat Rev Genet. 9. 179-191
  • Schroeder, DI, LaSalle, JM. (2013). How has the study of the human placenta aided our understanding of partially methylated genes?. Epigenomics....
  • Shah, S, McRae, AF, Marioni, RE, Harris, SE, Gibson, J, Henders, AK. (2014). Genetic and environmental exposures constrain epigenetic drift...
  • Shen, L, Song, CX, He, C, Zhang, Y. (2014). Mechanism and function of oxidative reversal of DNA and RNA methylation.. Annu Rev Biochem. 83....
  • Simpson, LJ, Patel, S, Bhakta, NR, Choy, DF, Brightbill, HD, Ren, X. (2014). A microRNA upregulated in asthma airway T cells promotes T. Nat...
  • Singh, V, Singh, LC, Singh, AP, Sharma, J, Borthakur, BB, Debnath, A. (2015). Status of epigenetic chromatin modification enzymes and esophageal...
  • (2005). limma: linear models for microarray data. In:. Springer. New York.
  • Sofer, T, Schifano, ED, Hoppin, JA, Hou, L, Baccarelli, AA. (2013). A-clustering: a novel method for the detection of co-regulated methylation...
  • Soubry, A, Murphy, SK, Wang, F, Huang, Z, Vidal, AC, Fuemmeler, BF. (2015). Newborns of obese parents have altered DNA methylation patterns...
  • Stricker, I, Tzivras, D, Nambiar, S, Wulf, J, Liffers, ST, Vogt, M. (2012). Site- and grade-specific diversity of. Anticancer Res. 32. 3699-3706
  • Su, Y, Subedee, A, Bloushtain-Qimron, N, Savova, V, Krzystanek, M, Li, L. (2015). Somatic cell fusions reveal extensive heterogeneity in basal-like...
  • Tan, Z, Randall, G, Fan, J, Camoretti-Mercado, B, Brockman-Schneider, R, Pan, L. (2007). Allele-specific targeting of microRNAs to. Am J Hum...
  • Tang, WW, Dietmann, S, Irie, N, Leitch, HG, Floros, VI, Bradshaw, CR. (2015). A unique gene regulatory network resets the human germline epigenome...
  • Tarantini, L, Bonzini, M, Tripodi, A, Angelici, L, Nordio, F, Cantone, L. (2013). Blood hypomethylation of inflammatory genes mediates the...
  • Teschendorff, AE, Zhuang, J, Widschwendter, M. (2011). Independent surrogate variable analysis to deconvolve confounding factors in large-scale...
  • Thompson, RF, Suzuki, M, Lau, KW, Greally, JM. (2009). A pipeline for the quantitative analysis of CG dinucleotide methylation using mass...
  • Tost, J, Gut, IG. (2007). DNA methylation analysis by pyrosequencing.. Nat Protoc. 2. 2265-2275
  • (2003). Unified Cross-Validation Methodology for Selection among Estimators and a General Cross-Validated Adaptive Epsilon-Net Estimator:...
  • (2011). Targeted Minimum Loss Based Estimation of an Intervention Specific Mean Outcome.. UC Berkeley Division of Biostatistics Working Paper...
  • (2011). Springer. New York.
  • (2009). Readings in Targeted Maximum Likelihood Estimation.. UC Berkeley Division of Biostatistics Working Paper Series. Working Paper 254....
  • (2006). Targeted Maximum Likelihood Learning.. UC Berkeley Division of Biostatistics Working Paper Series. Working Paper 213. Berkeley, CA.
  • van der Vaart, AW, Dudoit, S, van der Laan, MJ. (2006). Oracle inequalities for multi-fold cross-validation.. J Stat Decisions. 3. 351-371
  • Vidal, AC, Benjamin Neelon, SE, Liu, Y, Tuli, AM, Fuemmeler, BF, Hoyo, C. (2014). Maternal stress, preterm birth, and DNA methylation at imprint...
  • Vidal, AC, Murphy, SK, Murtha, AP, Schildkraut, JM, Soubry, A, Huang, Z. (2013). Associations between antibiotic exposure during pregnancy,...
  • Vilahur, N, Bustamante, M, Byun, HM, Fernandez, MF, Santa Marina, L, Basterrechea, M. (2014). Prenatal exposure to mixtures of xenoestrogens...
  • Wachter, A, Beißbarth, T. (2015). pwOmics: an R package for pathway-based integration of time-series omics data using public database knowledge.....
  • Waldrip, ZJ, Byrum, SD, Storey, AJ, Gao, J, Byrd, AK, Mackintosh, SG. (2014). A CRISPR-based approach for proteomic analysis of a single genomic...
  • Wang, D, Yan, L, Hu, Q, Sucheston, LE, Higgins, MJ, Ambrosone, CB. (2012). IMA: an R package for high-throughput analysis of Illumina’s 450K...
  • Wang, H, Rose, S, van der Laan, MJ. (2011). Finding quantitative trait loci genes with collaborative targeted maximum likelihood learning.....
  • Wei, L, Liu, B, Tuo, J, Shen, D, Chen, P, Li, Z. (2012). Hypomethylation of the. Cell Rep. 2. 1151-1158
  • Yang, X, Lay, F, Han, H, Jones, PA. (2010). Targeting DNA methylation for epigenetic therapy.. Trends Pharmacol Sci. 31. 536-546
  • Yousefi, P, Huen, K, Quach, H, Motwani, G, Hubbard, A, Eskenazi, B. (2015). Estimation of blood cellular heterogeneity in newborns and children...
  • Zeger, SL, Liang, KY, Albert, PS. (1988). Models for longitudinal data: a generalized estimating equation approach.. Biometrics. 44. 1049-1060
  • Zhang, YJ, Wu, HC, Yazici, H, Yu, MW, Lee, PH, Santella, RM. (2012). Global hypomethylation in hepatocellular carcinoma and its relationship...
  • Zierer, J, Menni, C, Kastenmüller, G, Spector, TD. (2015). Integration of ‘omics’ data in aging research: from biomarkers to systems biology.....
  • Zou, J, Lippert, C, Heckerman, D, Aryee, M, Listgarten, J. (2014). Epigenome-wide association studies without the need for cell-type composition.....