Digitizing Omics Profiles by Divergence from a Baseline
Digitizing omics profiles by divergence from a baseline INAUGURAL ARTICLE Wikum Dinalankaraa,1, Qian Keb,1, Yiran Xub, Lanlan Jib, Nicole Paganea, Anching Liena, Tejasvi Matama, Elana J. Fertiga, Nathan D. Pricec, Laurent Younesb, Luigi Marchionnia,2, and Donald Gemanb,2 aDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205; bDepartment of Applied Mathematics and Statistics, Johns Hopkins University, Baltimore, MD 21218; and cInstitute for Systems Biology, Seattle, WA 98109 This contribution is part of the special series of Inaugural Articles by members of the National Academy of Sciences elected in 2015. Contributed by Donald Geman, March 19, 2018 (sent for review December 13, 2017; reviewed by Nicholas P. Tatonetti and Bin Yu) Data collected from omics technologies have revealed perva- relative to a baseline, may be essential to fully realize the poten- sive heterogeneity and stochasticity of molecular states within tial of high-dimensional omics assays; in principle, they pro- and between phenotypes. A prominent example of such het- vide unprecedented quantification of normal and disease-specific erogeneity occurs between genome-wide mRNA, microRNA, and variation, which can inform clinical approaches for diagnosis and methylation profiles from one individual tumor to another, even prevention of complex diseases. within a cancer subtype. However, current methods in bioinfor- To develop this high-dimensional analogue to low-dimensional matics, such as detecting differentially expressed genes or CpG clinical tests, we present a unified framework to characterize sites, are population-based and therefore do not effectively model normal and nonnormal variation by quantizing high-resolution intersample diversity. Here we introduce a unified theory to quan- measurements into a few discrete states based on divergence tify sample-level heterogeneity that is applicable to a single omics from a baseline.
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