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Algorithm for cellular reprogramming

  1. Indika Rajapaksea,f,1
  1. aDepartment of Computational Medicine and Bioinformatics, Medical School, University of Michigan, Ann Arbor, MI 48109;
  2. bDepartment of Curriculum Design, IXL Learning, Raleigh, NC 27560;
  3. cDepartment of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, MI 48109;
  4. dDepartment of Biological Sciences, University of Maryland, College Park, MD 20742;
  5. eDepartment of Hematology/Oncology, University of Michigan, Ann Arbor, MI 48109;
  6. fDepartment of Mathematics, University of Michigan, Ann Arbor, MI 48109;
  7. gJohn A. Paulson School of Engineering and Applied Science, Harvard University, Cambridge, MA 02138
  1. Edited by Steven Henikoff, Fred Hutchinson Cancer Research Center, Seattle, WA, and approved September 26, 2017 (received for review July 14, 2017)

  1. Fig. 2.

    DGC overview. (A) Summary of control equation variables. (B) Each TAD is a node in a dynamic network. The blue connections represent the edges of the network and are determined from time series fibroblast RNA-seq data. The green plots represent the expression of each TAD changing over time. The red arrows indicate additional regulation imposed by exogenous TFs. (C) A conceptual illustration of the problem: Can we determine TFs to push the cell state from one basin to another?

  2. Fig. 3.

    Quantitative measure between cell types and TF scores. (A) <mml:math><mml:msub><mml:mi>d</mml:mi><mml:mn>0</mml:mn></mml:msub></mml:math>d0 values between GTEx tissue types and ESC, myotube, and fibroblast. Tissue types and cell types with black arrows have predicted TFs for reprogramming from fibroblasts shown in B. (B) Table of predicted TFs for a subset of cell and tissue types. Top five TFs for combinations of one to three are shown. Green labeled TFs are highly associated with the differentiation process of the target cell type and/or validated for reprogramming. These TFs are discussed in the main text. (C) Time-dependent scores for selected combinations of three TFs for fibroblast to ESC and fibroblast to “heart - left ventricle.” x axis refers to time of TF addition, and y axis refers to <mml:math><mml:mi>μ</mml:mi></mml:math>μ.

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