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

Author:

Stephens Dominique C.12,Crabtree Amber1,Beasley Heather K.1,Garza‐Lopez Edgar3,Mungai Margaret3,Vang Larry1,Neikirk Kit1,Vue Zer1,Vue Neng1,Marshall Andrea G.1,Turner Kyrin2,Shao Jian‐qiang4,Sarker Bishnu5,Murray Sandra6,Gaddy Jennifer A.78,Hinton Antentor O.1ORCID,Damo Steven2,Davis Jamaine9

Affiliation:

1. Department of Molecular Physiology and Biophysics Vanderbilt University Nashville TN 37232 USA

2. Department of Life and Physical Sciences Fisk University Nashville TN 37232 USA

3. Department of Internal Medicine University of Iowa Iowa City IA 52242 USA

4. Central Microscopy Research Facility University of Iowa Iowa City IA 52242 USA

5. School of Applied Computational Sciences Meharry Medical College Nashville TN 37208 USA

6. Department of Cell Biology College of Medicine University of Pittsburgh Pittsburgh PA 15260 USA

7. Division of Infectious Diseases Vanderbilt University School of Medicine Nashville TN 37232 USA

8. U.S. Department of Veterans Affairs Tennessee Valley Healthcare Systems Nashville TN 37212 USA

9. Department of Biochemistry and Cancer Biology Meharry Medical College Nashville TN 37208 USA

Abstract

AbstractMachine 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.

Publisher

Wiley

Subject

General Biochemistry, Genetics and Molecular Biology,Biomedical Engineering,Biomaterials

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