Penalized weighted low-rank approximation for robust recovery of recurrent copy number variations

2015-2016 UNCG University Libraries Open Access Publishing Fund Grant Winner. BackgroundCopy number variation (CNV) analysis has become one of the most important researchareas for understanding complex disease. With increasing resolution of array-basedcomparative genomic hybridization (aCGH) arrays, more and more raw copy numberdata are collected for multiple arrays. It is natural to realize the co-existence of bothrecurrent and individual-specific CNVs, together with the possible data contaminationduring the data generation process. Therefore, there is a great need for an efficient androbust statistical model for simultaneous recovery of both recurrent and individualspecificCNVs.ResultWe develop a penalized weighted low-rank approximation method (WPLA) for robustrecovery of recurrent CNVs. In particular, we formulate multiple aCGH arrays into arealization of a hidden low-rank matrix with some random noises and let an additionalweight matrix account for those individual-specific effects. Thus, we do not restrict therandom noise to be normally distributed, or even homogeneous. We show itsperformance through three real datasets and twelve synthetic datasets from different typesof recurrent CNV regions associated with either normal random errors or heavilycontaminated errors.ConclusionOur numerical experiments have demonstrated that the WPLA can successfully recoverthe recurrent CNV patterns from raw data under different scenarios. Compared with twoother recent methods, it performs the best regarding its ability to simultaneously detectboth recurrent and individual-specific CNVs under normal random errors. Moreimportantly, the WPLA is the only method which can effectively recover the recurrentCNVs region when the data is heavily contaminated

svt: Singular Value Thresholding in MATLAB

Many statistical learning methods such as matrix completion, matrix regression, and multiple response regression estimate a matrix of parameters. The nuclear norm regularization is frequently employed to achieve shrinkage and low rank solutions. To minimize a nuclear norm regularized loss function, a vital and most time-consuming step is singular value thresholding, which seeks the singular values of a large matrix exceeding a threshold and their associated singular vectors. Currently MATLAB lacks a function for singular value thresholding. Its built-in svds function computes the top r singular values/vectors by Lanczos iterative method but is only efficient for sparse matrix input, while aforementioned statistical learning algorithms perform singular value thresholding on dense but structured matrices. To address this issue, we provide a MATLAB wrapper function svt that implements singular value thresholding. It encompasses both top singular value decomposition and thresholding, handles both large sparse matrices and structured matrices, and reduces the computation cost in matrix learning algorithms

SS-adic expansions related to continued fractions (Natural extension of arithmetic algorithms and S-adic system)

"Natural extension of arithmetic algorithms and S-adic system". July 20～24, 2015. edited by Shigeki Akiyama. The papers presented in this volume of RIMS Kôkyûroku Bessatsu are in final form and refereed.We consider S-adic expansions associated with continued fraction algorithms, where an S-adic expansion corresponds to an infinite composition of substitutions. Recall that a substitution is a morphism of the free monoid. We focus in particular on the substitutions associated with regular continued fractions (Sturmian substitutions), and with Arnoux-Rauzy, Brun, and Jacobi{Perron (multidimensional) continued fraction algorithms. We also discuss the spectral properties of the associated symbolic dynamical systems under a Pisot type assumption

Machine Learning and System Identification for Estimation in Physical Systems

In this thesis, we draw inspiration from both classical system identification and modern machine learning in order to solve estimation problems for real-world, physical systems. The main approach to estimation and learning adopted is optimization based. Concepts such as regularization will be utilized for encoding of prior knowledge and basis-function expansions will be used to add nonlinear modeling power while keeping data requirements practical.The thesis covers a wide range of applications, many inspired by applications within robotics, but also extending outside this already wide field.Usage of the proposed methods and algorithms are in many cases illustrated in the real-world applications that motivated the research.Topics covered include dynamics modeling and estimation, model-based reinforcement learning, spectral estimation, friction modeling and state estimation and calibration in robotic machining.In the work on modeling and identification of dynamics, we develop regularization strategies that allow us to incorporate prior domain knowledge into flexible, overparameterized models. We make use of classical control theory to gain insight into training and regularization while using tools from modern deep learning. A particular focus of the work is to allow use of modern methods in scenarios where gathering data is associated with a high cost.In the robotics-inspired parts of the thesis, we develop methods that are practically motivated and make sure that they are implementable also outside the research setting. We demonstrate this by performing experiments in realistic settings and providing open-source implementations of all proposed methods and algorithms

Characterizing genetic intra-tumor heterogeneity across 2,658 human cancer genomes

Intra-tumor heterogeneity (ITH) is a mechanism of therapeutic resistance and therefore an important clinical challenge. However, the extent, origin, and drivers of ITH across cancer types are poorly understood. To address this, we extensively characterize ITH across whole-genome sequences of 2,658 cancer samples spanning 38 cancer types. Nearly all informative samples (95.1 %) contain evidence of distinct subclonal expansions with frequent branching relationships between subclones, We observe positive selection of subclonal driver mutations across most cancer types and identify cancer type-specific subclonal patterns of driver gene mutations, fusions, structural variants, and copy number alterations as well as dynamic changes in mutational processes between subclonal expansions. Our results underline the importance of ITH and its drivers in tumor evolution and provide a pan-cancer resource of comprehensively annotated subclonal events from whole-genome sequencing data.Peer reviewe

Characterizing genetic intra-tumor heterogeneity across 2,658 human cancer genomes.

Intra-tumor heterogeneity (ITH) is a mechanism of therapeutic resistance and therefore an important clinical challenge. However, the extent, origin, and drivers of ITH across cancer types are poorly understood. To address this, we extensively characterize ITH across whole-genome sequences of 2,658 cancer samples spanning 38 cancer types. Nearly all informative samples (95.1%) contain evidence of distinct subclonal expansions with frequent branching relationships between subclones. We observe positive selection of subclonal driver mutations across most cancer types and identify cancer type-specific subclonal patterns of driver gene mutations, fusions, structural variants, and copy number alterations as well as dynamic changes in mutational processes between subclonal expansions. Our results underline the importance of ITH and its drivers in tumor evolution and provide a pan-cancer resource of comprehensively annotated subclonal events from whole-genome sequencing data

Machine Learning, Low-Rank Approximations and Reduced Order Modeling in Computational Mechanics

The use of machine learning in mechanics is booming. Algorithms inspired by developments in the field of artificial intelligence today cover increasingly varied fields of application. This book illustrates recent results on coupling machine learning with computational mechanics, particularly for the construction of surrogate models or reduced order models. The articles contained in this compilation were presented at the EUROMECH Colloquium 597, « Reduced Order Modeling in Mechanics of Materials », held in Bad Herrenalb, Germany, from August 28th to August 31th 2018. In this book, Artificial Neural Networks are coupled to physics-based models. The tensor format of simulation data is exploited in surrogate models or for data pruning. Various reduced order models are proposed via machine learning strategies applied to simulation data. Since reduced order models have specific approximation errors, error estimators are also proposed in this book. The proposed numerical examples are very close to engineering problems. The reader would find this book to be a useful reference in identifying progress in machine learning and reduced order modeling for computational mechanics