A nonparametric statistical method for deconvolving densities in the analysis of proteomic data

TL;DR

This paper introduces NPFD, a novel nonparametric deconvolution method using Fourier transforms, designed to accurately estimate signal densities in proteomic data with high variance, outperforming existing methods.

Contribution

The paper proposes NPFD, a new Fourier-based deconvolution technique that effectively handles high-variance data, improving density estimation in proteomic and genomic studies.

Findings

NPFD performs better than existing methods in high-variance scenarios.

Application to real proteomic data successfully isolates extrinsic aging signals.

Simulation results confirm robustness and accuracy of NPFD.

Abstract

In medical research, often, genomic or proteomic data are collected, with measurements frequently subject to uncertainties or errors, making it crucial to accurately separate the signals of the genes or proteins, respectively, from the noise. Such a signal separation is also of interest in skin aging research in which intrinsic aging driven by genetic factors and extrinsic, i.e.\ environmentally induced, aging are investigated by considering, e.g., the proteome of skin fibroblasts. Since extrinsic influences on skin aging can only be measured alongside intrinsic ones, it is essential to isolate the pure extrinsic signal from the combined intrinisic and extrinsic signal. In such situations, deconvolution methods can be employed to estimate the signal's density function from the data. However, existing nonparametric deconvolution approaches often fail when the variance of the mixed distribution is substantially greater than the variance of the target distribution, which is a common issue in genomic and proteomic data. We, therefore, propose a new nonparametric deconvolution method called N-Power Fourier Deconvolution (NPFD) that addresses this issue by employing the $N$-th power of the Fourier transform of transformed densities. This procedure utilizes the Fourier transform inversion theorem and exploits properties of Fourier transforms of density functions to mitigate numerical inaccuracies through exponentiation, leading to accurate and smooth density estimation. An extensive simulation study demonstrates that NPFD effectively handles the variance issues and performs comparably or better than existing deconvolution methods in most scenarios. Moreover, applications to real medical data, particularly to proteomic data from fibroblasts affected by intrinsic and extrinsic aging, show how NPFD can be employed to estimate the pure extrinsic density.