Replication: We developed a method for analyzing Okazaki fragment sequencing (Ok-seq) data to quantitatively determine replication initiation and termination frequencies and to study genome-wide replication fork directionality (Kit Leng Lui & Keegan et al., Nature Protocols 2021). We applied this methods to study how transcription shapes DNA replication initiation and termination in human cells (Chen & Keegan et al., Nature Structural & Molecular Biology 2019), DNA replication stress and genomic instability (Coleman & Yin et al., Nature Communications 2022), and how dormant origin firing promotes head-on transcription-replication conflicts at transcription termination sites in response to BRCA2 deficiency (Goehring et al., Nature Communications 2024)

Retrotransposons: We are developing algorithms for analyzing retrotransposons, mobile DNA elements that make up a large portion of our genome and are able to through an RNA intermediary insert themselves into new genomic loci, including: (i) TIPseqHunter, a machine-learning-based pipeline for detection of novel LINE-1 insertions using targeted sequencing (Tang et al. PNAS 2019, Grivainis et al. Bioinformatics 2020), (ii) L1EM, a method for loci specific quantitation of full length LINE-1 transcripts that uses the expectation maximization algorithm to quantify LINE-1 RNA at each genomic locus, separating transcripts that are capable of generating retrotransposition from those that are not (McKerrow et al. Bioinformatics 2020) (iii) scL1seq, a method for quantifying LINE-1 transcripts in 5' single-cell RNA-Seq data (McKerrow et al. NAR 2023) and detecting novel insertions. (more ...)

Synthetic Biology: We are participating in The Dark Matter Project which aims to decipher the function of the non-coding genome.