For a full and up-to-date list, see my Google Scholar profile.
† indicates equal contribution.
Journal Articles
2025
Benchmarking of germline copy number variant callers from whole genome sequencing data for clinical applications.
Bioinformatics Advances, 5(1), vbaf071.
We benchmark several short-read WGS CNV detection tools using reference cell lines to inform their clinical use. Tools vary in sensitivity (7%–83%) and precision (1%–76%), with few meeting the sensitivity needed for clinical testing. Callers generally perform better for deletions (up to 88% sensitivity) than duplications (up to 47% sensitivity), with poor detection of duplications under 5 kb. For CNVs in genes commonly included in clinical panels, significantly improved sensitivity and precision were observed. DRAGEN v4.2 high-sensitivity CNV calls, post-processed with custom filters, achieved 100% sensitivity and 77% precision on the optimized gene panel after excluding recurring artifacts, which may support clinical use with orthogonal confirmation of reportable CNVs.
2023
Reproducible evaluation of transposable element detectors with McClintock 2 guides accurate inference of Ty insertion patterns in yeast.
Mobile DNA, 14, 8.
We report a completely re-implemented version of McClintock written in Python using Snakemake and Conda that improves installation, error handling, speed, stability, and extensibility. McClintock 2 now includes 12 short-read TE detectors, auxiliary pre-processing and analysis modules, interactive HTML reports, and a simulation framework to reproducibly evaluate the accuracy of component TE detectors. When applied to Saccharomyces cerevisiae, we find substantial variation in the ability of components to identify the precise locations of non-reference TE insertions, with RelocaTE2 showing the highest recall and precision in simulated data. Best-in-class predictors have sufficient resolution to reveal a dyad pattern of integration in nucleosome-bound regions upstream of yeast tRNA genes for Ty1, Ty2, and Ty4.
2022
Local assembly of long reads enables phylogenomics of transposable elements in a polyploid cell line.
Nucleic Acids Research, 50(21), e124.
Animal cell lines often undergo extreme genome restructuring, including polyploidy and segmental aneuploidy that can impede de novo whole-genome assembly. We developed a novel WGA-independent bioinformatics method called TELR that identifies, locally assembles, and estimates allele frequency of TEs from long-read sequence data. Application of TELR to a ~130x PacBio dataset for the tetraploid Drosophila S2R+ cell line revealed many haplotype-specific TE insertions that arose by transposition after initial cell line establishment and subsequent tetraploidization. Local assemblies from TELR also allowed phylogenetic analysis of paralogous TEs, revealing that proliferation of TE families in vitro can be driven by single or multiple source lineages.
2022
Ongoing transposition in cell culture reveals the phylogeny of diverse Drosophila S2 sublines.
Genetics, 221(3), iyac077.
Cultured cells are widely used in molecular biology despite poor understanding of how cell line genomes change in vitro over time. We sequenced the genomes of 25 Drosophila S2 cell sublines and show that transposable element insertions provide abundant markers for the phylogenetic reconstruction of diverse sublines. Our analysis revealed dramatically different patterns of genome organization across sublines and supported a model of ongoing transposition dominated by episodic activity of a small number of retrotransposon families. We conclude that substantial genome evolution occurs during long-term Drosophila cell culture, which may impact the reproducibility of experiments that do not control for subline identity.
2022
A novel transposable element-based authentication protocol for Drosophila cell lines.
G3: Genes, Genomes, Genetics, 12(2), jkab403.
Drosophila cell lines are used by researchers to investigate various cell biological phenomena, yet methods to authenticate them are lacking. We developed a PCR-based next-generation sequencing protocol to cluster cell lines based on the genome-wide distribution of a limited number of diagnostic TE families. The protocol reliably identified various Drosophila cell lines during double-blind testing, and showed minimal changes with respect to TE family distribution when cells are passaged for at least 50 times. We conclude that this approach can accurately identify and distinguish the numerous Drosophila cell lines available to the research community, thereby aiding reproducible cell culture research.
2021
Transposable element profiles reveal cell line identity and loss of heterozygosity in Drosophila cell culture.
Genetics, 219(2), iyab113.
We leverage the classical observation that transposable elements (TEs) proliferate in cultured Drosophila cells to demonstrate that genome-wide TE insertion profiles can reveal the identity and provenance of Drosophila cell lines. We identify multiple cases where TE profiles clarify the origin of cell lines (Sg4, mbn2, and OSS_E) relative to published reports, and provide evidence that insertions from only a subset of LTR retrotransposon families are necessary to mark cell line identity. We also develop ngs_te_mapper2, a bioinformatics approach to detect TE insertions and estimate intra-sample allele frequencies in legacy WGS data, which revealed loss of heterozygosity as a mechanism shaping the unique TE profiles that identify Drosophila cell lines.
2017
Genomic analysis of P elements in natural populations of Drosophila melanogaster.
PeerJ, 5, e3824.
We compared estimates of genomic P element content with gonadal dysgenesis phenotypes for isofemale strains from three worldwide populations of D. melanogaster. P element abundance is highly correlated across different bioinformatics approaches, but sensitive to method and filtering strategy. North American strains have fewer P elements but a higher proportion of full-length elements than European or African strains. However, geographic differences in P element abundance and structure are not associated with corresponding differences in dysgenesis. We conclude that genomic P element content alone is not sufficient to explain variation in gonadal dysgenesis across strains.
Patents
2024
2024
2024
Thesis
2021
Novel computational strategies for the analysis of transposable elements in Drosophila cell culture genomes.
Ph.D. Dissertation, University of Georgia.