I'm currently working as a postdoctoral research associate with the Griffith lab where we are investigating the genomic architecture of cancer.
My ongoing interest is in the development of computational tools to aid in visualization, interpretation, and discovery of clinically relevant genomic events to aid precision medicine efforts in cancer.
In one project, we are improving the Drug-Gene Interaction Database (DGIdb), a web resource that consolidates disparate data sources describing drug-gene interactions and gene druggability. It provides an intuitive graphical user interface and a documented application programming interface (API) for querying these data. DGIdb was assembled through an extensive manual curation effort, reflecting the combined information of twenty-seven sources. For DGIdb 2.0, substantial updates have been made to increase content and improve its usefulness as a resource for mining clinically actionable drug targets. We have demonstrated the utility of DGIdb in a precision medicine workflow in a patient with acute lymphocytic leukemia.
In another project, we are investigating the genomics of relapsed and chemo-resistant small cell lung cancers (SCLCs), using a combination of exome and transcriptome sequencing to profile the primary and relapsed tumors of 17 patients with SCLC. This work has led to identification of key genetic alterations that appear to be specific or strongly enriched in chemo-resistant SCLCs (manuscript under review).
My Ph.D. work was under the mentorship of Terry Braun at the University of Iowa's Coordinated Laboratory for Computational Genomics. For my doctoral dissertation, I studied computational methods for identification of disease-associated variations in exome sequencing. While there, I developed a method for predicting genetic variants associated with heritable retinal dystrophies, using a novel machine learning strategy (PULP).
Another focus of my work was on improving the accuracy of the CLCG variant detection pipeline. Working with Dr. Edwin Stone at the Wynn Institute for Vision Research, we developed a technique for identifying synonymous and intronic variants that were associated with Stargardt's Disease through integrating patient exome data with control (reference) transcriptome sequence. We also developed a model for improving the specificity of detected variants from our exome sequencing experiments.
Finally, I developed web resources to help characterize healthy and diseased retinal tissue. The ocular tissue database (OTDB) provides a look at expression of 10 tissues of the human eye, while the TRIPOD web tool (manuscript in preparation) provides an interface for the study and evaluation of phenotypic and genotypic associations in rare, heritable retinal dystrophies.
AH Wagner, AC Coffman, BJ Ainscough, NC Spies, ZL Skidmore, KM Campbell, K Krysiak, D Pan, JF McMichael, JM Eldred, JR Walker, RK Wilson, ER Mardis, M Griffith*, OL Griffith* (2015) "DGIdb 2.0: mining clinically relevant drug-gene interactions". Nucleic acids research. doi: 10.1093/nar/gkv1165.
SS Whitmore, AH Wagner, AP DeLuca, AV Drack, EM Stone, BA Tucker, S Zeng, TA Braun, RF Mullins, TE Scheetz (2014) "Transcriptomic analysis across nasal, temporal, and macular regions of human neural retina and RPE/choroid by RNA-Seq". Experimental Eye Research. doi:10.1016/j.exer.2014.11.001
TP Sharma, CM McDowell, Y Liu, AH Wagner, D Thole, BP Faga, RJ Workinger, TA Braun, AF Clark (2014) "Optic nerve crush induces spatial and temporal gene expression patterns in retina and optic nerve of BALB/cJ mice". Molecular Neurodegeneration. doi: 10.1186/1750-1326-9-14
TA Braun, RF Mullins, AH Wagner, J Andorf, R Johnston, B Bakall, AP DeLuca, G Fisherman, R Weleber, A Cideciyan, S Jacobson, V Sheffield, B Tucker, EM Stone (2013) "Non-exomic and synonymous variants in ABCA4 are an important cause of Stargardt disease". Human Molecular Genetics. doi: 10.1093/hmg/ddt367
AH Wagner, KR Taylor, AP DeLuca, TL Casavant, RF Mullins, EM Stone, TE Scheetz, TA Braun (2013), "Prioritization of Retinal Disease Genes: An Integrative Approach." Human Mutation. doi: 10.1002/humu.22317
AH Wagner, VN Anand, W Wang, JE Chatterton, D Sun, AR Shepard, N Jacobson, L Pang, AP DeLuca, TL Casavant, TE Scheetz, RF Mullins, TA Braun, AF Clark (2013) "Exon-level expression profiling of ocular tissues". Experimental Eye Research. doi: 10.1016/j.exer.2013.03.004
AP DeLuca, AH Wagner, KR Taylor, B Faga, D Thole, VC Sheffield, EM Stone, TL Casavant, TE Scheetz, TA Braun (December 2011) "Sequencing and disease variation detection tools and techniques". 9th IEEE/ACS International Conference on Computer Systems and
*Authors contributed equally to the work.
|CIViC is a community knowledgebase for expert crowdsourcing the clinical interpretation of variants in cancer||Nat Genet. 2017 Jan 31;49(2):170-174. doi: 10.1038/ng.3774.||2017-01-31|
|DoCM: a database of curated mutations in cancer.||Nat Methods. 2016 Sep 29;13(10):806-7. doi: 10.1038/nmeth.4000.||1970-08-22|
|CIViC: A knowledgebase for expert-crowdsourcing the clinical interpretation of variants in cancer||doi: http://dx.doi.org/10.1101/072892|
|GenVisR: Genomic Visualizations in R.||Bioinformatics. 2016 Jun 10. pii: btw325. [Epub ahead of print]||2016-06-10|
|Comprehensive genomic analysis reveals FLT3 activation and a therapeutic strategy for a patient with relapsed adult B-lymphoblastic leukemia||Exp Hematol. 2016 Jul;44(7):603-13. doi: 10.1016/j.exphem.2016.04.011. Epub 2016 May 13||2016-07-01|
|DGIdb 2.0: mining clinically relevant drug-gene interactions.||Nucleic Acids Res. 2015 Nov 3. pii: gkv1165. [Epub ahead of print]||2015-11-03|