Distributed estimation from relative measurements of heterogeneous and uncertain quality

This paper studies the problem of estimation from relative measurements in a graph, in which a vector indexed over the nodes has to be reconstructed from pairwise measurements of differences between its components associated to nodes connected by an edge. In order to model heterogeneity and uncertainty of the measurements, we assume them to be affected by additive noise distributed according to a Gaussian mixture. In this original setup, we formulate the problem of computing the Maximum-Likelihood (ML) estimates and we design two novel algorithms, based on Least Squares regression and Expectation-Maximization (EM). The first algorithm (LS- EM) is centralized and performs the estimation from relative measurements, the soft classification of the measurements, and the estimation of the noise parameters. The second algorithm (Distributed LS-EM) is distributed and performs estimation and soft classification of the measurements, but requires the knowledge of the noise parameters. We provide rigorous proofs of convergence of both algorithms and we present numerical experiments to evaluate and compare their performance with classical solutions. The experiments show the robustness of the proposed methods against different kinds of noise and, for the Distributed LS-EM, against errors in the knowledge of noise parameters.Comment: Submitted to IEEE transaction

TrAp: a Tree Approach for Fingerprinting Subclonal Tumor Composition

Revealing the clonal composition of a single tumor is essential for identifying cell subpopulations with metastatic potential in primary tumors or with resistance to therapies in metastatic tumors. Sequencing technologies provide an overview of an aggregate of numerous cells, rather than subclonal-specific quantification of aberrations such as single nucleotide variants (SNVs). Computational approaches to de-mix a single collective signal from the mixed cell population of a tumor sample into its individual components are currently not available. Herein we propose a framework for deconvolving data from a single genome-wide experiment to infer the composition, abundance and evolutionary paths of the underlying cell subpopulations of a tumor. The method is based on the plausible biological assumption that tumor progression is an evolutionary process where each individual aberration event stems from a unique subclone and is present in all its descendants subclones. We have developed an efficient algorithm (TrAp) for solving this mixture problem. In silico analyses show that TrAp correctly deconvolves mixed subpopulations when the number of subpopulations and the measurement errors are moderate. We demonstrate the applicability of the method using tumor karyotypes and somatic hypermutation datasets. We applied TrAp to SNV frequency profile from Exome-Seq experiment of a renal cell carcinoma tumor sample and compared the mutational profile of the inferred subpopulations to the mutational profiles of twenty single cells of the same tumor. Despite the large experimental noise, specific co-occurring mutations found in clones inferred by TrAp are also present in some of these single cells. Finally, we deconvolve Exome-Seq data from three distinct metastases from different body compartments of one melanoma patient and exhibit the evolutionary relationships of their subpopulations

A Semi-Blind Source Separation Method for Differential Optical Absorption Spectroscopy of Atmospheric Gas Mixtures

Differential optical absorption spectroscopy (DOAS) is a powerful tool for detecting and quantifying trace gases in atmospheric chemistry \cite{Platt_Stutz08}. DOAS spectra consist of a linear combination of complex multi-peak multi-scale structures. Most DOAS analysis routines in use today are based on least squares techniques, for example, the approach developed in the 1970s uses polynomial fits to remove a slowly varying background, and known reference spectra to retrieve the identity and concentrations of reference gases. An open problem is to identify unknown gases in the fitting residuals for complex atmospheric mixtures. In this work, we develop a novel three step semi-blind source separation method. The first step uses a multi-resolution analysis to remove the slow-varying and fast-varying components in the DOAS spectral data matrix $X$. The second step decomposes the preprocessed data $\hat{X}$ in the first step into a linear combination of the reference spectra plus a remainder, or $\hat{X} = A\,S + R$, where columns of matrix $A$ are known reference spectra, and the matrix $S$ contains the unknown non-negative coefficients that are proportional to concentration. The second step is realized by a convex minimization problem $S = \mathrm{arg} \min \mathrm{norm}\,(\hat{X} - A\,S)$, where the norm is a hybrid $\ell_1/\ell_2$ norm (Huber estimator) that helps to maintain the non-negativity of $S$. The third step performs a blind independent component analysis of the remainder matrix $R$ to extract remnant gas components. We first illustrate the proposed method in processing a set of DOAS experimental data by a satisfactory blind extraction of an a-priori unknown trace gas (ozone) from the remainder matrix. Numerical results also show that the method can identify multiple trace gases from the residuals.Comment: submitted to Journal of Scientific Computin

Partial-volume Bayesian classification of material mixtures in MR volume data using voxel histograms

The authors present a new algorithm for identifying the distribution of different material types in volumetric datasets such as those produced with magnetic resonance imaging (MRI) or computed tomography (CT). Because the authors allow for mixtures of materials and treat voxels as regions, their technique reduces errors that other classification techniques can create along boundaries between materials and is particularly useful for creating accurate geometric models and renderings from volume data. It also has the potential to make volume measurements more accurately and classifies noisy, low-resolution data well. There are two unusual aspects to the authors' approach. First, they assume that, due to partial-volume effects, or blurring, voxels can contain more than one material, e.g., both muscle and fat; the authors compute the relative proportion of each material in the voxels. Second, they incorporate information from neighboring voxels into the classification process by reconstructing a continuous function, ρ(x), from the samples and then looking at the distribution of values that ρ(x) takes on within the region of a voxel. This distribution of values is represented by a histogram taken over the region of the voxel; the mixture of materials that those values measure is identified within the voxel using a probabilistic Bayesian approach that matches the histogram by finding the mixture of materials within each voxel most likely to have created the histogram. The size of regions that the authors classify is chosen to match the sparing of the samples because the spacing is intrinsically related to the minimum feature size that the reconstructed continuous function can represent