低温电磁场和多时间维三维电影中的连续异质超对象
Continuously heterogeneous hyper-objects in cryo-EM and 3-D movies of many temporal dimensions
摘要：
单粒子低温电子显微镜（EM）是一种越来越流行的方法，用于从取向和位置随机且未知的单个大分子的噪声2-D图像确定大分子的3-D结构。冷冻电镜的一个巨大机会是恢复异质样品中大分子的结构，其中多种类型或多种构象混合在一起。事实上，近年来，已经引入了许多工具来分析在冷冻EM实验中混合在一起的多个离散类分子。然而，许多有趣的结构有一个连续的构象，不适合离散模型很好，这种连续异质模型的分析仍然是一个更难以捉摸的目标。在这篇手稿中，我们提出了代表异质分子和类似的结构作为更高的维度对象。我们概括了许多现有的重建算法中使用的基本操作，使我们的方法通用的意义上说，在原则上，现有的算法可以适应重建这些更高的维度的对象。作为概念证明，我们提出了一个新的算法，我们用来解决模拟重建问题的原型。
英文摘要：
Single particle cryo-electron microscopy (EM) is an increasingly popular method for determining the 3-D structure of macromolecules from noisy 2-D images of single macromolecules whose orientations and positions are random and unknown. One of the great opportunities in cryo-EM is to recover the structure of macromolecules in heterogeneous samples, where multiple types or multiple conformations are mixed together. Indeed, in recent years, many tools have been introduced for the analysis of multiple discrete classes of molecules mixed together in a cryo-EM experiment. However, many interesting structures have a continuum of conformations which do not fit discrete models nicely; the analysis of such continuously heterogeneous models has remained a more elusive goal. In this manuscript, we propose to represent heterogeneous molecules and similar structures as higher dimensional objects. We generalize the basic operations used in many existing reconstruction algorithms, making our approach generic in the sense that, in principle, existing algorithms can be adapted to reconstruct those higher dimensional objects. As proof of concept, we present a prototype of a new algorithm which we use to solve simulated reconstruction problems.
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