Amit Singer: Software for near-atomic resolution using cryo-electron microscopy

Sept. 7, 2019

A software package aims to aid drug design and biomedical research by making it easy to construct 3D images of proteins and other molecules using one of the world’s most powerful microscopes. Amit Singer, professor of mathematics and the Program in Applied and Computational Mathematics, and his team are developing a package they call Algorithms for Single Particle Reconstruction, or ASPIRE, that takes in 2D images captured by cryo-electron microscopy and produces reliable 3D structures without significant human intervention.

The package will offer fully automated and faster data processing, producing highly accurate images. Whereas existing software packages require human input on which images to include in analysis, ASPIRE needs little user modification, reducing the potential for bias. Unlike today’s software, which starts with an initial estimate of the 3D structure, ASPIRE does not make any initial assumptions but rather relies only on the images themselves. The team’s long-term goal is to develop a commercial software package that will make biomolecular structures more readily available for drug discovery and research.

Team members: Nicolas Boumal, assistant professor of mathematics; postdoctoral research associates Tamir Ben Dory, Ayelet Heimowitz, Joseph Kileel, Ti-Yen Lan and Amit Moscovich; former postdoctoral research associates Joakim Anden, Roy Lederman and Nir Sharon; graduate student Amit Halevi; research software engineers Vineet Bansal and Junchao Xia; and undergraduate Eitan Levin, Class of 2020.

Collaborators: Frederick Sigworth, professor of cellular and molecular physiology and of biomedical engineering and of molecular biophysics and biochemistry at Yale School of Medicine, and Yoel Shkolnisky, professor of applied mathematics at Tel Aviv University

Development status: Patent protection is pending. Princeton is seeking outside interest for the development of this technology.

Funding: National Institutes of Health, Simons Foundation, Gordon and Betty Moore Foundation

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