Walking along chromosomes with super-resolution imaging, contact maps, and integrative modeling.

Chromosome organization is crucial for genome function. Here, we present a method for visualizing chromosomal DNA at super-resolution and then integrating Hi-C data to produce three-dimensional models of chromosome organization. Using the super-resolution microscopy methods of OligoSTORM and OligoDNA-PAINT, we trace 8 megabases of human chromosome 19, visualizing structures ranging in size from a few kilobases to over a megabase. Focusing on chromosomal regions that contribute to compartments, we discover distinct structures that, in spite of considerable variability, can predict whether such regions correspond to active (A-type) or inactive (B-type) compartments. Imaging through the depths of entire nuclei, we capture pairs of homologous regions in diploid cells, obtaining evidence that maternal and paternal homologous regions can be differentially organized. Finally, using restraint-based modeling to integrate imaging and Hi-C data, we implement a method-integrative modeling of genomic regions (IMGR)-to increase the genomic resolution of our traces to 10 kb.

Sample drift correction in 3D fluorescence photoactivation localization microscopy.

The recent development of diffraction-unlimited far-field fluorescence microscopy has overcome the classical resolution limit of ~250 nm of conventional light microscopy by about a factor of ten. The improved resolution, however, reveals not only biological structures at an unprecedented resolution, but is also susceptible to sample drift on a much finer scale than previously relevant. Without correction, sample drift leads to smeared images with decreased resolution, and in the worst case to misinterpretation of the imaged structures. This poses a problem especially for techniques such as Fluorescence Photoactivation Localization Microscopy (FPALM/PALM) or Stochastic Optical Reconstruction Microscopy (STORM), which often require minutes recording time. Here we discuss an approach that corrects for three-dimensional (3D) drift in images of fixed samples without the requirement for fiduciary markers or instrument modifications. Drift is determined by calculating the spatial cross-correlation function between subsets of localized particles imaged at different times. Correction down to ~5 nm precision is achieved despite the fact that different molecules are imaged in each frame. We demonstrate the performance of our drift correction algorithm with different simulated structures and analyze its dependence on particle density and localization precision. By imaging mitochondria with Biplane FPALM we show our algorithm's feasibility in a practical application.

VisComplete: automating suggestions for visualization pipelines.

Building visualization and analysis pipelines is a large hurdle in the adoption of visualization and workflow systems by domain scientists. In this paper, we propose techniques to help users construct pipelines by consensus--automatically suggesting completions based on a database of previously created pipelines. In particular, we compute correspondences between existing pipeline subgraphs from the database, and use these to predict sets of likely pipeline additions to a given partial pipeline. By presenting these predictions in a carefully designed interface, users can create visualizations and other data products more efficiently because they can augment their normal work patterns with the suggested completions. We present an implementation of our technique in a publicly-available, open-source scientific workflow system and demonstrate efficiency gains in real-world situations.

Streaming simplification of tetrahedral meshes.

Unstructured tetrahedral meshes are commonly used in scientific computing to represent scalar, vector, and tensor fields in three dimensions. Visualization of these meshes can be difficult to perform interactively due to their size and complexity. By reducing the size of the data, we can accomplish real-time visualization necessary for scientific analysis. We propose a two-step approach for streaming simplification of large tetrahedral meshes. Our algorithm arranges the data on disk in a streaming, I/O-efficient format that allows coherent access to the tetrahedral cells. A quadric-based simplification is sequentially performed on small portions of the mesh in-core. Our output is a coherent streaming mesh which facilitates future processing. Our technique is fast, produces high quality approximations, and operates out-of-core to process meshes too large for main memory.

Progressive volume rendering of large unstructured grids.

We describe a new progressive technique that allows real-time rendering of extremely large tetrahedral meshes. Our approach uses a client-server architecture to incrementally stream portions of the mesh from a server to a client which refines the quality of the approximate rendering until it converges to a full quality rendering. The results of previous steps are re-used in each subsequent refinement, thus leading to an efficient rendering. Our novel approach keeps very little geometry on the client and works by refining a set of rendered images at each step. Our interactive representation of the dataset is efficient, light-weight, and high quality. We present a framework for the exploration of large datasets stored on a remote server with a thin client that is capable of rendering and managing full quality volume visualizations.

Hardware-assisted visibility sorting for unstructured volume rendering.

Harvesting the power of modern graphics hardware to solve the complex problem of real-time rendering of large unstructured meshes is a major research goal in the volume visualization community. While, for regular grids, texture-based techniques are well-suited for current GPUs, the steps necessary for rendering unstructured meshes are not so easily mapped to current hardware. We propose a novel volume rendering technique that simplifies the CPU-based processing and shifts much of the sorting burden to the GPU, where it can be performed more efficiently. Our hardware-assisted visibility sorting algorithm is a hybrid technique that operates in both object-space and image-space. In object-space, the algorithm performs a partial sort of the 3D primitives in preparation for rasterization. The goal of the partial sort is to create a list of primitives that generate fragments in nearly sorted order. In image-space, the fragment stream is incrementally sorted using a fixed-depth sorting network. In our algorithm, the object-space work is performed by the CPU and the fragment-level sorting is done completely on the GPU. A prototype implementation of the algorithm demonstrates that the fragment-level sorting achieves rendering rates of between one and six million tetrahedral cells per second on an ATI Radeon 9800.