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Center for Computational Mass-Spectrometry

Vineet Bafna, Ph.D., Nuno Bandeira, Ph.D., Pavel A. Pevzner, Ph.D.
2P41GM103484
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Center Overview

Center for Computational Mass Spectrometry (CCMS) is a national and international resource in the area of proteomics aimed at branching into previously unexplored areas of computational proteomics and supporting multiple collaborative efforts. The Center focuses on the computational bottlenecks that affects the entire proteomics community and impair interpretation of data in thousands of experimental labs. The goal of CCMS is to bring the modern algorithmic approaches to mass-spectrometry and to build a new generation of reliable open access software tools to support both new mass-spectrometry instrumentation and the emerging applications. The proposal focuses on four directions:

  1. enabling complex mass spectrometry searches,
  2. analyzing unknown proteomes without protein databases,
  3. analyzing altered proteomes, and
  4. constructing proteogenomic annotations.

These directions cover both well-studied but still inadequately addressed problems and unexplored problems for which there are no computational tools currently available (like antibody and antibiotics sequencing). These projects require collaborative efforts on a wide range of topics involving biomedical scientists from various institutions. The biomedical applications addressed at CCMS include but are not limited to:

  1. de novo sequencing of antibodies that proved to be valuable pharmaceuticals,
  2. understanding how bacteria adjust to antibiotics,
  3. new approach to analyzing antibiotics that speeds up the process of new antibiotics characterization by order(s) of magnitude,
  4. combining next generation sequencing and mass spectrometry for analyzing human microbiome,
  5. characterization of human neuropeptides. CCMS also develops various educational and dissemination activities that include the organization of the first annual conference in the area of computational proteomics and associated short courses.

Impact on Human Health

The mission of CCMS is to develop new computational proteomics approaches that contribute to various biomedical applications. CCMS is a leader in the development of new disruptive technologies for two key directions in drug discovery: search for new therapeutic monoclonal antibodies (mAbs) and search for new antibiotics aimed at drug-resistant diseases. CCMS is a key partner in many academic and industrial collaborations aimed at various biomedical problems such as that studies of human neuropeptides and characterizing protein modifications in patients with sickle cell traits.

While the therapeutic market for monoclonal antibodies has grown exponentially in the last 10 years (8 of the 20 best-selling biotechnology drugs are mAbs), the mAb discovery efforts face an important computational bottleneck since sequencing antibodies with existing approaches is extremely difficult. Jointly with Genentech, a leader in antibody industry, CCMS developed a new disruptive proteomics approach to sequencing mAbs that is order(s) of magnitude faster than previous approaches.

New antibiotics discovery is another important area that faces a computational bottleneck since existing NMR-based approaches to antibiotics characterization are very time-consuming and require large amounts of purified antibiotics that are often unavailable. CCMS developed an alternative mass spectrometry (rather than NMR) approach to antibiotics sequencing that is very fast and requires only minimal amount of unpurified antibiotics. In contrast to the existing approach (that sequence one antibiotics at a time), the approach developed at CCMS is the first multiplex approach to antibiotics sequencing when multiple compounds from a sample are rapidly sequenced at once.

CCMS also works on bridging genomics and proteomics to enable new previously infeasible biomedical applications. For example, metaproteomics studies of human microbiome are currently limited since most human microbes cannot be cloned in the lab and thus cannot be sequenced. CCMS (jointly with Venter Institute and Illumina) recently developed a computational technology for sequencing genomes from single cells thus removing a key roadblock for biomedical applications of metaproteomics.