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This paper presents a nonparametric statistical modeling method for quantifying uncertainty in stochastic gradient systems with isotropic diffusion. The central idea is to apply the diffusion maps algorithm to a training data set to produce a stochastic matrix whose generator is a discrete approximation to the backward Kolmogorov operator of the underlying dynamics. The eigenvectors of this stochastic matrix, which we will refer to as the diffusion coordinates, are discrete approximations to the eigenfunctions of the Kolmogorov operator and form an orthonormal basis for functions defined on the data set. Using this basis, we consider the projection of three uncertainty quantification (UQ) problems (prediction, filtering, and response) into the diffusion coordinates. In these coordinates, the nonlinear prediction and response problems reduce to solving systems of infinite-dimensional linear ordinary differential equations …