Browsing by Author "Wheeler, David A."

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    Detection and characterization of constitutive replication origins defined by DNA polymerase epsilon
    (Springer Nature, 2023) Jaksik, Roman; Wheeler, David A.; Kimmel, Marek
    Despite the process of DNA replication being mechanistically highly conserved, the location of origins of replication (ORI) may vary from one tissue to the next, or between rounds of replication in eukaryotes, suggesting flexibility in the choice of locations to initiate replication. Lists of human ORI therefore vary widely in number and location, and there are currently no methods available to compare them. Here, we propose a method of detection of ORI based on somatic mutation patterns generated by the mutator phenotype of damaged DNA polymerase epsilon (POLE).
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    ITD assembler: an algorithm for internal tandem duplication discovery from short-read sequencing data
    (BioMed Central, 2016) Rustagi, Navin; Hampton, Oliver A.; Li, Jie; Xi, Liu; Gibbs, Richard A.; Plon, Sharon E.; Kimmel, Marek; Wheeler, David A.
    Abstract Background Detection of tandem duplication within coding exons, referred to as internal tandem duplication (ITD), remains challenging due to inefficiencies in alignment of ITD-containing reads to the reference genome. There is a critical need to develop efficient methods to recover these important mutational events. Results In this paper we introduce ITD Assembler, a novel approach that rapidly evaluates all unmapped and partially mapped reads from whole exome NGS data using a De Bruijn graphs approach to select reads that harbor cycles of appropriate length, followed by assembly using overlap-layout-consensus. We tested ITD Assembler on The Cancer Genome Atlas AML dataset as a truth set. ITD Assembler identified the highest percentage of reported FLT3-ITDs when compared to other ITD detection algorithms, and discovered additional ITDs in FLT3, KIT, CEBPA, WT1 and other genes. Evidence of polymorphic ITDs in 54 genes were also found. Novel ITDs were validated by analyzing the corresponding RNA sequencing data. Conclusions ITD Assembler is a very sensitive tool which can detect partial, large and complex tandem duplications. This study highlights the need to more effectively look for ITD’s in other cancers and Mendelian diseases.