Welcome to Software Development at the NCMI
The National Center for Macromolecular Imaging (NCMI) is a research facility primarily focused on electron cryomicroscopy (cryo-EM) of molecules and macromolecular assemblies. Using various techniques it is now possible to obtain 3-D structures of such specimens at subnanometer resolution. Our mission is to develop this technology and make it accessible to the scientific community. We are equipped with state of the art electron cryomicroscopes, sample preparation equipment, including vitrification robots and computational resources for 3-D reconstructions. A significant portion of our resources is devoted to developing software for data acquisition, 3-D reconstructions, structural analysis and visualization of the results.
In electron cryomicroscopy, numerous challenges must be overcome to achieve subnanometer resolution structures. An electron beam can very easily damage a biological specimen, thus as few electrons as possible must be used to observe high-resolution features of macromolecules. This requirement means that the signal to noise ratio of each image is also very low. To compensate for this, tens to hundreds of thousands of images of the same kind of molecule are collected to boost the signal to noise ratio in the final 3-D reconstruction. Current reconstructions require datasets on the order of tens of gigabytes, but the amount of data required to achieve higher resolutions will double for every angstrom gained in resolution. Macromolecules by their very nature are complex assemblies of proteins and/or nucleic acids. Dissecting and analyzing these 3-D reconstructions and their various components is a significant challenge in itself. Our work has resulted in a collection of software packages that work in a number of computational environments to meet the diverse challenges in pushing the limits of cryo-EM.
EMEN (Electron Microscopy Electronic Notebook) is an object-oriented database used to record information about all aspects of transmission electron microscopy experiments, from specimen purification through final 3D reconstruction. EMEN is built on top of the object-oriented database and web-based application server, ZOPE. Several of the applications produced at the NCMI now interface with this database to deposit and retrieve data and metadata when necessary. After a year of use, EMEN serves approximately 3 TB of data contained in 2.1 million records.
JAMES (JEOL Automated Microscopy Expert System) is a software package designed to facilitate high-resolution electron cryomicroscopy. JAMES runs on Windows to integrate several commercial software packages necessary to operate a modern electron cryomicroscope. It intelligently handles several of the repetitive procedures performed by a skilled electron microscopist in collecting high-resolution data. JAMES is fully integrated with our database so data, and the corresponding metadata, can be automatically deposited.
EMAN (Electron Microscopy ANalysis) is a scientific image processing suite, aimed at improving the resolution and quality of single particle reconstructions. At its foundation is a flexible C++ library with complete Python bindings. Through the high level commands/GUI, single particle reconstructions can be performed with minimal human effort to subnanometer resolutions. EMAN is our most mature and comprehensive software package and as a result is at the core of software development at NCMI. We are currently prototyping a grid-enabled version of this package.
SAVR (Semi-Automated Virus Reconstruction) is a suite of programs intended to make image processing simple and rapid for icosahedral 3-D reconstructions to subnanometer resolution. SAVR, an expert system that integrates the most CPU intensive and iterative steps using Python, is portable across platforms and has been parallelized to run on both shared and distributed memory platforms. SAVR also allows the incorporation of new algorithms and facilitates the management of the increasingly large data sets needed to achieve higher resolution reconstructions.
AIRS (Analysis of Intermediate Resolution Structures) is a suite of programs designed to facilitate the analysis of intermediate resolution structures. AIRS has been built on top of the existing EMAN libraries and is currently part of the EMAN distribution. Included in AIRS are programs to identity alpha helices (helixhunter), dock folds/domains to a macromolecule (foldhunter) and image filters, such as the bilateral filter. With a subnanometer resolution cryo-EM map, AIRS is capable of integrating sequence-derived information or atomic coordinate information with the cryo-EM map to yield pseudo-atomic models. Currently, AIRS software is available via a command line interface or through a graphical interface in both UCSF's Chimera and IRIS Explorer.
SAIL (Scientific Animation Integration Library) is a collection of modules developed under IRIS Explorer for the 3-D visualization and data management of large macromolecule structures. Contained within the SAIL modules is the ability to read, write, segment, analyze and annotate the various types of 3-D datasets. Also included with SAIL is an animation toolkit for the construction of MPEG/MPEG2 animations.