title: Omic personality: implications of stable transcript and methylation profiles for personalized medicine.
abstract: BACKGROUND
  Personalized medicine is predicated on the notion that individual biochemical and genomic profiles are relatively constant in times of good health and to some extent predictive of disease or therapeutic response. We report a pilot study quantifying gene expression and methylation profile consistency over time, addressing the reasons for individual uniqueness, and its relation to N = 1 phenotypes.
  
  
  METHODS
  Whole blood samples from four African American women, four Caucasian women, and four Caucasian men drawn from the Atlanta Center for Health Discovery and Well Being study at three successive 6-month intervals were profiled by RNA-Seq, miRNA-Seq, and Illumina Methylation 450 K arrays. Standard regression approaches were used to evaluate the proportion of variance for each type of omic measure among individuals, and to quantify correlations among measures and with clinical attributes related to wellness.
  
  
  RESULTS
  Longitudinal omic profiles were in general highly consistent over time, with an average of 67 % variance in transcript abundance, 42 % in CpG methylation level (but 88 % for the most differentiated CpG per gene), and 50 % in miRNA abundance among individuals, which are all comparable to 74 % variance among individuals for 74 clinical traits. One third of the variance could be attributed to differential blood cell type abundance, which was also fairly stable over time, and a lesser amount to expression quantitative trait loci (eQTL) effects. Seven conserved axes of covariance that capture diverse aspects of immune function explained over half of the variance. These axes also explained a considerable proportion of individually extreme transcript abundance, namely approximately 100 genes that were significantly up-regulated or down-regulated in each person and were in some cases enriched for relevant gene activities that plausibly associate with clinical attributes. A similar fraction of genes had individually divergent methylation levels, but these did not overlap with the transcripts, and fewer than 20 % of genes had significantly correlated methylation and gene expression.
  
  
  CONCLUSIONS
  People express an "omic personality" consisting of peripheral blood transcriptional and epigenetic profiles that are constant over the course of a year and reflect various types of immune activity. Baseline genomic profiles can provide a window into the molecular basis of traits that might be useful for explaining medical conditions or guiding personalized health decisions.
authors.affiliation: Center for Integrative Genomics, School of Biology, Georgia Institute of Technology, Boggs Building 1-96, 770 State Street, Atlanta, GA, 30332, USA. rubina.tabassum@helsinki.fi.|Institute for Molecular Medicine Finland, Helsinki, Finland. rubina.tabassum@helsinki.fi.
authors.forename: Rubina
authors.initials: R
authors.lastname: Tabassum
authors.affiliation: Center for Integrative Genomics, School of Biology, Georgia Institute of Technology, Boggs Building 1-96, 770 State Street, Atlanta, GA, 30332, USA. Ambily.sivadas@gmail.com.|CSIR-Institute of Genomics and Integrative Biology, Delhi, India. Ambily.sivadas@gmail.com.
authors.forename: Ambily
authors.initials: A
authors.lastname: Sivadas
authors.affiliation: Center for Integrative Genomics, School of Biology, Georgia Institute of Technology, Boggs Building 1-96, 770 State Street, Atlanta, GA, 30332, USA. vartikaagrawal198@gmail.com.|Philips Health Care, Briarcliff Manor, NY, USA. vartikaagrawal198@gmail.com.
authors.forename: Vartika
authors.initials: V
authors.lastname: Agrawal
authors.affiliation: Center for Integrative Genomics, School of Biology, Georgia Institute of Technology, Boggs Building 1-96, 770 State Street, Atlanta, GA, 30332, USA. tianhzh@gatech.edu.
authors.forename: Haozheng
authors.initials: H
authors.lastname: Tian
authors.affiliation: Center for Integrative Genomics, School of Biology, Georgia Institute of Technology, Boggs Building 1-96, 770 State Street, Atlanta, GA, 30332, USA. darafat.gt@gmail.com.
authors.forename: Dalia
authors.initials: D
authors.lastname: Arafat
authors.affiliation: Center for Integrative Genomics, School of Biology, Georgia Institute of Technology, Boggs Building 1-96, 770 State Street, Atlanta, GA, 30332, USA. greg.gibson@biology.gatech.edu.
authors.forename: Greg
authors.initials: G
authors.lastname: Gibson
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D020869:Gene Expression Profiling; D023281:Genomics; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics; D008875:Middle Aged; D010865:Pilot Projects; D057285:Precision Medicine; D017423:Sequence Analysis, RNA; D014158:Transcription, Genetic; D044465:White People / Q000235:genetics
chemical_list: D035683:MicroRNAs