In the Age of Machine Learning Cryo-EM Research is Still Necessary: A Path toward Precision Medicine.

Journal: Advanced biology
Published Date:

Abstract

Machine learning has proven useful in analyzing complex biological data and has greatly influenced the course of research in structural biology and precision medicine. Deep neural network models oftentimes fail to predict the structure of complex proteins and are heavily dependent on experimentally determined structures for their training and validation. Single-particle cryogenic electron microscopy (cryoEM) is also advancing the understanding of biology and will be needed to complement these models by continuously supplying high-quality experimentally validated structures for improvements in prediction quality. In this perspective, the significance of structure prediction methods is highlighted, but the authors also ask, what if these programs cannot accurately predict a protein structure important for preventing disease? The role of cryoEM is discussed to help fill the gaps left by artificial intelligence predictive models in resolving targetable proteins and protein complexes that will pave the way for personalized therapeutics.

Authors

  • Dominique C Stephens
    Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA.
  • Amber Crabtree
    Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA.
  • Heather K Beasley
    Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA.
  • Edgar Garza-Lopez
    Department of Internal Medicine, University of Iowa, Iowa City, IA, 52242, USA.
  • Margaret Mungai
    Department of Internal Medicine, University of Iowa, Iowa City, IA, 52242, USA.
  • Larry Vang
    Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA.
  • Kit Neikirk
    Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA.
  • Zer Vue
    Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA.
  • Neng Vue
    Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA.
  • Andrea G Marshall
    Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA.
  • Kyrin Turner
    Department of Life and Physical Sciences, Fisk University, Nashville, TN, 37232, USA.
  • Jian-Qiang Shao
    Central Microscopy Research Facility, University of Iowa, Iowa City, IA, 52242, USA.
  • Bishnu Sarker
    School of Applied Computational Sciences, Meharry Medical College, Nashville, TN, 37208, USA.
  • Sandra Murray
    Department of Cell Biology, College of Medicine, University of Pittsburgh, Pittsburgh, PA, 15260, USA.
  • Jennifer A Gaddy
    Division of Infectious Diseases, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA.
  • Antentor O Hinton
    Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA.
  • Steven Damo
    Department of Life and Physical Sciences, Fisk University, Nashville, TN, 37232, USA.
  • Jamaine Davis
    Department of Biochemistry and Cancer Biology, Meharry Medical College, Nashville, TN, 37208, USA.