Mapping your life and everything else – the promise of high dimensional phenomics

John A. McLean

Stevenson Professor of Chemistry

Senior Associate Dean of Graduate Education and Research – College of Arts & Science Director of the Center for Innovative Technology

Vanderbilt University, Nashville, TN

Abstract:

The human genome project is recognized as being one of the most successful big science projects in modern history. One of the primary motivations to undertake the HGP was to better understand what made us human and healthy. While the frontiers of our knowledge expanded dramatically, we also uncovered profound biological complexity that we could not understand. This led to the current frontier in the measurement science of molecular phenomics, to catalog the broad-scale changes in the molecular inventory in cells, tissues, and biological fluids at a specific biological state, or in response to exposures and lifestyle choices. In phenomics, we seek to characterize the comprehensive molecular basis of biology, in both space and time. This places enormous demands on measurement technologies and computational approaches to organize the millions of potential species present in vanishingly small spatial coordinates. Ion mobility-mass spectrometry (IM-MS) provides rapid (ms) gas-phase electrophoretic separations on the basis of molecular structure and is well suited for integration with rapid (us) mass spectrometry detection techniques to meet these analytical challenges. This report will describe recent advances in IM-MS integrated omics measurement strategies in the analyses of complex biological samples of interest in systems, synthetic, and chemical biology. New advances in artificial intelligence and machine learning will also be described to approach biological queries from an unbiased and untargeted perspective and to quickly mine these massive datasets. While enormous challenges remain, the promise is immense – comprehensive diagnostics and predictive capabilities for health and medicine of importance to society and beyond.

Short Biosketch:

John A. McLean is Stevenson Professor of Chemistry, Senior Associate Dean of Graduate Education and Research, and Director of the Center for Innovative Technologies at Vanderbilt University. He is an elected Fellow of the National Academy of Inventors, the American Association for the Advancement of Science, and the Royal Society of Chemistry. He completed his PhD at George Washington University, postdoctoral research at Forschungszentrum Jülich in Germany (under the direction of Dr. Sabine Becker) and then at Texas A&M University (under the direction of Prof. David H. Russell) – before beginning at Vanderbilt University in 2006. He rapidly rose through the ranks and served as chair of the chemistry department for four years and chair of the Faculty Senate before moving into his present role. McLean and colleagues have focused on the conceptualization, design, and construction of ion mobility and structural mass spectrometers, specifically targeting complex samples in systems, synthetic, and chemical biology. His group applies these strategies to forefront translational research areas in drug discovery, personalized medicine, and ‘human-on-chip’ synthetic biology platforms. Prof. McLean has received a number of awards, including the Agilent Thought Leader Award, Waters Center of Innovation, the Chancellor’s Award for Research, the Thomas Jefferson Award, Excellence in Teaching Award from the student members of the American Chemical Society, a Defense Threat Reduction Agency Research Award, an American Society for Mass Spectrometry Research Award, and the Bunsen–Kirchhoff Prize from the GDCh (German Chemical Society), among others. He has published over 200 manuscripts and received over 30 patents in these and allied areas.