Summary

Cancer immune responses to radiation therapy are marked by profound molecular and cellular heterogeneity.
This project leverages high-throughput sequencing (HT-seq) data to decode this heterogeneity from two systems
of interest that are involved in immune responses: a) transcriptomes and b) adaptive immune receptor repertoires
(AIRRs), including T- and B-cell receptor repertoires. The key question asked in this project is: Can we identify
robust signatures of radiation-induced responses in transcriptomes and AIRRs despite the noise and variability
inherent to HT-seq data from cancer samples? Furthermore, we aim to link the radiation-induced changes in the
composition of AIRRs to transcriptomic shifts, and evaluate these findings as potential biomarkers predictive of
treatment outcomes.

To achieve these aims, we propose a two-tiered approach. First, we will develop and use computational methods for
HT-seq data analysis from radio-oncological experiments, enabling quantitative detection of radiation-induced
changes in immune cell populations over time, as a function of radiation dose, and across patients. Second,
we will integrate these outputs into probabilistic Bayesian models to quantify radiation-driven perturbations while
explicitly accounting for biological heterogeneity.

Selected Publications

Kitanovski S, Cao Y, Ttoouli D, Farahpour F, Wang J, Hoffmann D. scBubbletree: computational approach for visualization of single cell RNA-seq data. BMC Bioinformatics 25, 302 (2024). https://doi.org/10.1186/s12859-024-05927-y

Kitanovski S, Horemheb-Rubio G, Adams O, Gärtner B, Lengauer T, Hoffmann D, Kaiser R. Rhinovirus prevalence as indicator for efficacy of measures against SARS-CoV-2. BMC Public Health 21, 1178 (2021). https://doi.org/10.1186/s12889-021-11178-w

Cao Y, Kitanovski S, Küppers R, Hoffmann D. UMI or not UMI, that is the question for scRNA-seq zero-inflation. Nat Biotechnol 39, 158–159 (2021). https://doi.org/10.1038/s41587-020-00810-6

Kitanovski S and Hoffmann D. IgGeneUsage: differential gene usage in immune repertoires, Bioinformatics, Volume 36, Issue 11, June 2020, Pages 3590–3591. https://doi.org/10.1093/bioinformatics/btaa174

Tucci FA, Kitanovski S, Johansson P, Klein-Hitpass L, Kahraman A, Dürig J, Hoffmann D, Küppers R. Biased IGH VDJ gene repertoire and clonal expansions in B cells of chronically hepatitis C virus–infected individuals. Blood 2018; 131 (5): 546–557. doi: https://doi.org/10.1182/blood-2017-09-805762