Research Paper Volume 6, Issue 12 pp 1033—1048
Stochastic modeling indicates that aging and somatic evolution in the hematopoietic system are driven by non-cell-autonomous processes
Figure 4. Mutation DFE affects the mutation accumulation slope.
(A) Mutation accumulation in the Tier 3 genome of AML (see inset for blowup of AMKL in children). (B) DNA methylation accumulation at neutral CpG islands of the human genome with age (from Horvath, 2013). (C-D) Simulated mutation accumulation in Tier 3 under mutation DFE variance σ= 0.000005 (C) and σ= 0.0005 (D) and different mutation rate fold increases over lifetime. (E) Simulated mutation accumulation in Tier 3 under stable mutation rate over lifetime and different mutation DFE variance. (F) The range (shaded) of mutation DFE variance (Y axis) and mutation fold rate increase over lifetime (X axis) that replicate WGS-derived slope of mutation accumulation in AML genomes and DNA methylation accumulation in the hematopoietic tissue within 95% confidence interval.