Applying statistical methods to elucidate biological mechanisms
I’m a PhD candidate in the Bioinformatics and Integrative Genomics program at Harvard. Previously, I completed my undergraduate and Master’s studies at the University of Toronto in Canada. My research interests include machine learning and deep learning applied to transposable elements, alternative splicing, 3D chromatin architecture, and epigenomics.
Looking for full-time positions starting in early 2026! Please get in touch :) danielle.denisko@gmail.com
Background: Changes in RNA splicing over the course of evolution have profoundly diversified the functional landscape of the human genome. While DNA sequences proximal to intron-exon junctions are known to be critical for RNA splicing, the impact of distal intronic sequences remains underexplored. Emerging evidence suggests that inverted pairs of intronic Alu elements can promote exon skipping by forming RNA stem-loop structures. However, their prevalence and influence throughout evolution remain unknown. Results: Here, we present a systematic analysis of inverted Alu pairs across the human genome to assess their impact on exon skipping through predicted RNA stem-loop formation and their relevance to hominoid evolution. We found that inverted Alu pairs, particularly pairs of AluY-AluSx1 and AluSz-AluSx, are enriched in the flanking regions of skippable exons genome-wide and are predicted to form stable stem-loop structures. Exons defined by weak 3’ acceptor and strong 5’ donor splice sites appear especially prone to this skipping mechanism. Through comparative genome analysis across nine primate species, we identified 67,126 hominoid-specific Alu insertions, primarily from AluY and AluS subfamilies, which form inverted pairs enriched across skippable exons in genes of ubiquitination-related pathways. Experimental validation of exon skipping among several hominoid-specific inverted Alu pairs further reinforced their potential evolutionary significance. Conclusion: This work extends our current knowledge of the roles of RNA secondary structure formed by inverted Alu pairs and details a newly emerging mechanism through which transposable elements have contributed to genomic innovation across hominoid evolution at the transcriptomic level.
@article{IRAlu,author={Denisko, Danielle and Kim, Jeonghyeon and Ku, Jayoung and Zhao, Boxun and Lee, Eunjung Alice},title={{Inverted Alu repeats in loop-out exon skipping across hominoid evolution}},journal={bioRxiv [Preprint]},year={2025},doi={10.1101/2025.03.07.642063},url={https://doi.org/10.1101/2025.03.07.642063},eprint={https://www.biorxiv.org/content/10.1101/2025.03.07.642063v1.full.pdf},}
Motif elucidation in ChIP-seq datasets with a knockout control
Danielle Denisko, Coby Viner, and Michael M Hoffman
Chromatin immunoprecipitation-sequencing is widely used to find transcription factor binding sites, but suffers from various sources of noise. Knocking out the target factor mitigates noise by acting as a negative control. Paired wild-type and knockout (KO) experiments can generate improved motifs but require optimal differential analysis. We introduce peaKO—a computational method to automatically optimize motif analyses with KO controls, which we compare to two other methods. PeaKO often improves elucidation of the target factor and highlights the benefits of KO controls, which far outperform input controls.PeaKO is freely available at https://peako.hoffmanlab.org.michael.hoffman@utoronto.ca
@article{peaKO,author={Denisko, Danielle and Viner, Coby and Hoffman, Michael M},title={{Motif elucidation in ChIP-seq datasets with a knockout control}},journal={Bioinformatics Advances},volume={3},number={1},pages={vbad031},year={2023},issn={2635-0041},doi={10.1093/bioadv/vbad031},url={https://doi.org/10.1093/bioadv/vbad031},eprint={https://academic.oup.com/bioinformaticsadvances/article-pdf/3/1/vbad031/49761827/vbad031.pdf},}
Classification and interaction in random forests
Danielle Denisko, and Michael M Hoffman
Proceedings of the National Academy of Sciences, 2018
@article{Denisko2018,author={Denisko, Danielle and Hoffman, Michael M},doi={10.1073/pnas.1800256115},issn={0027-8424},journal={Proceedings of the National Academy of Sciences},mendeley-groups={Commentary},number={8},pages={1690--1692},pmid={29440440},title={{Classification and interaction in random forests}},url={http://www.pnas.org/content/115/8/1690.abstract},volume={115},year={2018},}
