Due to continual advances in sequencing and other “omics” technologies, biology is experiencing a big data revolution. Computational methods are required not only to interpret newly sequenced genomes, but also search through a vast quantity of existing data to reveal previously uncharacterized biology.

Research in the Doxey lab uses computational methods to mine unexplored genomes for new genes and functions. Research in the lab involves a cycle of bioinformatic prediction and experimental characterization. Our primary research goals are:

  1. Development of new protein function-prediction methods
  2. Detection of functional shifts in protein families
  3. Discovery and characterization of novel protein families

We develop methods that combine sequence analysis with structural bioinformatics to predict and experimentally validate protein functions of interest. Currently, we are focusing efforts on predicting new families and functions of bacterial flagellins, clostridial toxins, and proteolytic enzymes.

Selected papers

  • Eckhard U, Bandukwala H, Mansfield MJ, Marino G, Cheng J, Wallace I, Holyoak T, Charles TC, Austin JW, Overall CM, Doxey AC. (2017) Discovery of a proteolytic flagellin family in diverse bacterial phyla that assembles enzymatically active flagella. Nature Communications, 8:521. [link]
  • Lobb B, Doxey AC. (2016) Novel function discovery through sequence and structural data mining. Current Opinion in Structural Biology, 38:53-61. [pubmed]
  • Mansfield M, Adams J, Doxey AC. (2015) Botulinum neurotoxin homologs outside of Clostridium. FEBS Letters, 589:342-8. [pubmed]
  • We combine sequence analysis, phylogenetics and structural modeling to pinpoint adaptive events in genes and genomes. We are interested in inferring mechanisms of neofunctionalization and functional divergence in protein families as well as non-coding regulatory elements.

    Selected Papers

    • Adams J, Mansfield MJ, Richard DJ, Doxey AC. (2016) Lineage-specific mutational clustering in protein structures predicts evolutionary shifts in function. Bioinformatics, 33:1338-1345. [pubmed]
    • Doxey AC, Yaish MW, Moffatt BA, Griffith M, McConkey BJ. (2007) Functional divergence in the Arabidopsis beta-1,3-glucanase gene family inferred by phylogenetic reconstruction of expression states. Molecular Biology and Evolution, 24:1045-1055. [pubmed]

    The Doxey Lab is also developing computational approaches to functionally annotate metagenomes and detect biologically relevant differences between them. Recent work includes the development of the MetAnnotate framework for combined taxonomic and functional profiling of metagenomic datasets.

    Selected Papers

    • Petrenko P, Lobb B, Kurtz DA, Neufeld JD, Doxey AC. (2015) MetAnnotate: function-specific taxonomic profiling and comparison of metagenomes. BMC Biology, 13:92. [pubmed]
    • Lobb B, Kurtz DA, Moreno-Hagelsieb G, Doxey AC. (2015) Remote homology and the functions of metagenomic dark matter. Frontiers in Genetics. [pubmed]
    • Doxey AC, Kurtz DA, Lynch MDJ, Sauder LA, Neufeld JD. (2015) Aquatic metagenomes implicate Thaumarchaeota in global cobalamin production. ISME J, 9:461-71. [pubmed]