splicekit: a comprehensive platform for differential splicing analysis of short-read RNA-seq data

In July 2022 I joined Roche in Basel, Switzerland, being part of a group of scientists working on research and development of small molecules that change splicing patterns and could potentially become novel drugs. One part of the work is doing lots of short-read RNA-seq splicing analysis to see how diverse molecules actually change splicing in a genome-wide context.

For this, we are developing splicekit, a platform that identifies targets (exons) that undergo splicing changes. Below a few slides and details on how the analysis and visualizations look like. This is a small part of what we do and that I can share outside of Roche.

Small molecules splicing modulators are becoming a thing in drug development and could present novel and important opportunities to alleviate and cure diverse diseases (Schneider-Poetsch et al, 2021). In fact Roche put to market the first FDA approved splicing modulator drug risdiplam (Ratni et al., 2018) to treat spinal muscular atrophy.

Research in this are is booming (also in terms of investments) and there are many many open questions and many many things to do and look into. Exciting times. I also presented splicekit at the Slovenian VTIS bioinformatics meeting, video here:

Thanks for reading and if it was helpful to you, leave a comment below.


 Ratni, H., Ebeling, M., Baird, J., Bendels, S., Bylund, J., Chen, K. S., Denk, N., Feng, Z., Green, L., Guerard, M., Jablonski, P., Jacobsen, B., Khwaja, O., Kletzl, H., Ko, C. P., Kustermann, S., Marquet, A., Metzger, F., Mueller, B., Naryshkin, N.A., Paushkin S.V., Pinard, E., Poirier, A., Reutlinger, M., Weetall, M., Zeller, A., Zhao, X., Mueller, L. (2018). Discovery of Risdiplam, a Selective Survival of Motor Neuron-2 (SMN2) Gene Splicing Modifier for the Treatment of Spinal Muscular Atrophy (SMA). Journal of Medicinal Chemistry, 61(15), 6501–6517. https://doi.org/10.1021/acs.jmedchem.8b00741
 Schneider-Poetsch, T., Chhipi-Shrestha, J. K., & Yoshida, M. (2021). Splicing modulators: on the way from nature to clinic. In Journal of Antibiotics (Vol. 74, Issue 10, pp. 603–616). Springer Nature. https://doi.org/10.1038/s41429-021-00450-1
 Lightfoot, H. L., & Smith, G. F. (2023). Targeting RNA with small molecules a safety perspective. British Journal of Pharmacology. https://doi.org/10.1111/bph.16027