标题： 使用快速组LARS的多个aCGH轮廓联合分割 显示英文标题

标题： Joint segmentation of many aCGH profiles using fast group LARS

摘要： 基于数组的比较基因组杂交(aCGH)是一种用于搜索拷贝数变异基因组区域的方法。 对于给定的aCGH图谱，一个挑战是准确地将其分割成恒定拷贝数的区域。 具有相同疾病状态的受试者，例如某种癌症，通常具有相似的拷贝数变异的aCGH图谱，这是由于与该特定疾病相关的扩增和缺失所致。 我们引入了一种约束优化算法，可以联合分割许多受试者的aCGH图谱。 它同时惩罚一组图谱在称为断点的基因组位置从一个恒定拷贝数水平跳变到另一个水平的自由度。 我们表明，被许多不同图谱共享的断点往往会首先被算法找到，即使在存在大量噪声的情况下也是如此。 该算法可以表述为一个群体LARS问题。 我们提出了一种极其快速的方法来找到解路径，即按重要性顺序的一系列共享断点。 在没有额外成本的情况下，该算法将所有aCGH图谱平滑成等拷贝数的分段常数区域，从而给出原始数据的低维版本。 这些可以在一张图表上对所有图谱进行展示，允许直观的视觉解释。 提供了模拟以及在膀胱癌aCGH图谱上的算法实现。 显示英文摘要

摘要： Array-Based Comparative Genomic Hybridization (aCGH) is a method used to search for genomic regions with copy numbers variations. For a given aCGH profile, one challenge is to accurately segment it into regions of constant copy number. Subjects sharing the same disease status, for example a type of cancer, often have aCGH profiles with similar copy number variations, due to duplications and deletions relevant to that particular disease. We introduce a constrained optimization algorithm that jointly segments aCGH profiles of many subjects. It simultaneously penalizes the amount of freedom the set of profiles have to jump from one level of constant copy number to another, at genomic locations known as breakpoints. We show that breakpoints shared by many different profiles tend to be found first by the algorithm, even in the presence of significant amounts of noise. The algorithm can be formulated as a group LARS problem. We propose an extremely fast way to find the solution path, i.e., a sequence of shared breakpoints in order of importance. For no extra cost the algorithm smoothes all of the aCGH profiles into piecewise-constant regions of equal copy number, giving low-dimensional versions of the original data. These can be shown for all profiles on a single graph, allowing for intuitive visual interpretation. Simulations and an implementation of the algorithm on bladder cancer aCGH profiles are provided.