title: Poly-omic prediction of complex traits: OmicKriging.
abstract: High-confidence prediction of complex traits such as disease risk or drug response is an ultimate goal of personalized medicine. Although genome-wide association studies have discovered thousands of well-replicated polymorphisms associated with a broad spectrum of complex traits, the combined predictive power of these associations for any given trait is generally too low to be of clinical relevance. We propose a novel systems approach to complex trait prediction, which leverages and integrates similarity in genetic, transcriptomic, or other omics-level data. We translate the omic similarity into phenotypic similarity using a method called Kriging, commonly used in geostatistics and machine learning. Our method called OmicKriging emphasizes the use of a wide variety of systems-level data, such as those increasingly made available by comprehensive surveys of the genome, transcriptome, and epigenome, for complex trait prediction. Furthermore, our OmicKriging framework allows easy integration of prior information on the function of subsets of omics-level data from heterogeneous sources without the sometimes heavy computational burden of Bayesian approaches. Using seven disease datasets from the Wellcome Trust Case Control Consortium (WTCCC), we show that OmicKriging allows simple integration of sparse and highly polygenic components yielding comparable performance at a fraction of the computing time of a recently published Bayesian sparse linear mixed model method. Using a cellular growth phenotype, we show that integrating mRNA and microRNA expression data substantially increases performance over either dataset alone. Using clinical statin response, we show improved prediction over existing methods. We provide an R package to implement OmicKriging (http://www.scandb.org/newinterface/tools/OmicKriging.html).
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, Illinois, United States of America.
authors.forename: Heather E
authors.initials: HE
authors.lastname: Wheeler
authors.forename: Keston
authors.initials: K
authors.lastname: Aquino-Michaels
authors.forename: Eric R
authors.initials: ER
authors.lastname: Gamazon
authors.forename: Vassily V
authors.initials: VV
authors.lastname: Trubetskoy
authors.forename: M Eileen
authors.initials: ME
authors.lastname: Dolan
authors.forename: R Stephanie
authors.initials: RS
authors.lastname: Huang
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Cox
authors.forename: Hae Kyung
authors.initials: HK
authors.lastname: Im
mesh_terms: D001499:Bayes Theorem; D016022:Case-Control Studies; D048708:Cell Growth Processes / Q000235:genetics; D008078:Cholesterol, LDL / Q000097:blood; D019295:Computational Biology / Q000379:methods*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics; D008957:Models, Genetic; D020412:Multifactorial Inheritance / Q000235:genetics*; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics; D019821:Simvastatin / Q000494:pharmacology; D012984:Software; D049490:Systems Biology / Q000379:methods; D013997:Time Factors
chemical_list: D008078:Cholesterol, LDL; D035683:MicroRNAs; D012333:RNA, Messenger; D019821:Simvastatin
keywords: Kriging; complex trait prediction; polygenic modeling; polygenic prediction; systems biology