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Selecting Medically Relevant In Vitro Protein Characterization Projects with a High Potential For Success
Author(s) -
Zajac Diana,
Tucker Brady,
Cotsoradis Alicia,
Mallmann Clara,
Cassidy Christine,
Gur Daniel
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.913.7
Subject(s) - missense mutation , biology , computer science , computational biology , biochemistry , phenotype , gene
As of November 2016, well over one‐third of the more than 170,000 unique variation records in ClinVar are of unknown importance; these variants are either (a) characterized as variants of unknown significance (VUS), (b) have no clinical significance provided, or (c) list conflicting reports of clinical significance. The vast number of ambiguous entries in ClinVar offer an opportunity for researchers seeking new projects in the area of in vitro protein characterization; not only are there many variants to choose from, the size of the dataset provides potential to select targets that are a good fit for the capabilities of the lab. The opportunity to preselect medically relevant projects with a higher degree of success is especially intriguing for researchers at undergraduate institutions, who do not have the resources of larger labs. We describe the development of a selection algorithm for choosing an in vitro protein characterization project that is amenable to undergraduate research. Our approach combines information from ClinVar and the Protein Databank to select enzymes with published crystal structures of the human protein, that have been previously expressed and purified in e. coli , and that feature at least one missense VUS entry in ClinVar. We also describe progress on the characterization of four variants of unknown significance in Glucose‐6‐Phosphate Dehydrogenase, an enzyme associated with hemolytic anemia. Support or Funding Information Support provided by DePauw University and the Howard Burkett Scholar Fund.