Structural heterogeneity in single-particle cryo-electron microscopy (cryo-EM) data represents a major challenge for high-resolution structure determination. Unsupervised classification may serve as the first step in the assessment of structural heterogeneity. However, traditional algorithms for unsupervised classification, such as K-means clustering and maximum likelihood optimization, may classify images into wrong classes with decreasing signal-to-noise-ratio (SNR) in the image data, yet demand increased computational costs. Overcoming these limitations requires further development of clustering algorithms for high-performance cryo-EM data processing. Here we introduce an unsupervised single-particle clustering algorithm derived from a statistical manifold learning framework called generative topographic mapping (GTM). We show that unsupervised GTM clustering improves classification accuracy by about 40% in the absence of input references for data with lower SNRs. Applications to several experimental datasets suggest that our algorithm can detect subtle structural differences among classes via a hierarchical clustering strategy. After code optimization over a high-performance computing (HPC) environment, our software implementation was able to generate thousands of reference-free class averages within hours in a massively parallel fashion, which allows a significant improvement on ab initio 3D reconstruction and assists in the computational purification of homogeneous datasets for high-resolution visualization.

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One of the key challenges in three-dimensional (3D) medical imaging is to enable the fast turn-around time, which is often required for interactive or real-time response. This inevitably requires not only high computational power but also high memory bandwidth due to the massive amount of data that need to be processed. In this work, we have developed a software platform that is designed to support high-performance 3D medical image processing for a wide range of applications using increasingly available and affordable commodity computing systems: multi-core, clusters, and cloud computing systems. To achieve scalable, high-performance computing, our platform (1) employs size-adaptive, distributable block volumes as a core data structure for efficient parallelization of a wide range of 3D image processing algorithms; (2) supports task scheduling for efficient load distribution and balancing; and (3) consists of a layered parallel software libraries that allow a wide range of medical applications to share the same functionalities. We evaluated the performance of our platform by applying it to an electronic cleansing system in virtual colonoscopy, with initial experimental results showing a 10 times performance improvement on an 8-core workstation over the original sequential implementation of the system.

We present Parallel Prophet, which projects potential parallel speedup from an annotated serial program before actual parallelization. Programmers want to see how much speedup could be obtained prior to investing time and effort to write parallel code. With Parallel Prophet, programmers simply insert annotations that describe the parallel behavior of the serial program. Parallel Prophet then uses lightweight interval profiling and dynamic emulations to predict potential performance benefit. Parallel Prophet models many realistic features of parallel programs: unbalanced workload, multiple critical sections, nested and recursive parallelism, and specific thread schedulings and paradigms, which are hard to model in previous approaches. Furthermore, Parallel Prophet predicts speedup saturation resulting from memory and caches by monitoring cache hit ratio and bandwidth consumption in a serial program.We achieve very small runtime overhead: approximately a 1.2-10 times slowdown and moderate memory consumption. We demonstrate the effectiveness of Parallel Prophet in eight benchmarks in the OmpSCR and NAS Parallel benchmarks by comparing our predictions with actual parallelized code. Our simple memory model also identifies performance limitations resulting from memory system contention.