title: "The molecule's the thing:" the promise of molecular modeling and dynamic simulations in aiding the prioritization and interpretation of genomic testing results.
abstract: Clinical genomics is now a reality and lies at the heart of individualized medicine efforts. The success of these approaches is evidenced by the increasing volume of publications that report causal links between genomic variants and disease. In spite of early success, clinical genomics currently faces significant challenges in establishing the relevance of the majority of variants identified by next generation sequencing tests. Indeed, the majority of mutations identified are harbored by proteins whose functions remain elusive. Herein we describe the current scenario in genomic testing and in particular the burden of variants of uncertain significance (VUSs). We highlight a role for molecular modeling and molecular dynamic simulations as tools that can significantly increase the yield of information to aid in the evaluation of pathogenicity. Though the application of these methodologies to the interpretation of variants identified by genomic testing is not yet widespread, we predict that an increase in their use will significantly benefit the mission of clinical genomics for individualized medicine.
authors: Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, 55905, USA; Center for Individualized Medicine, Mayo Clinic, Rochester, MN, 55905, USA.
authors: Gavin R
authors: GR
authors: Oliver
authors: Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, 55905, USA.
authors: Michael T
authors: MT
authors: Zimmermann
authors: Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, 55905, USA; Center for Individualized Medicine, Mayo Clinic, Rochester, MN, 55905, USA.
authors: Eric W
authors: EW
authors: Klee
authors: Center for Individualized Medicine, Mayo Clinic, Rochester, MN, 55905, USA; Laboratory of Epigenetics and Chromatin Dynamics, Epigenomics Translational Program, Gastroenterology Research Unit, Departments of Biochemistry and Molecular Biology, Biophysics, and Medicine, Mayo Clinic, Rochester, MN, 55905, USA.
authors: Raul A
authors: RA
authors: Urrutia
keywords: Clinical Genomics; Diagnostic Odyssey; Individualized Medicine; Molecular Dynamics; Molecular Modeling; Oncology; Variants of Unknown Significance