News

Together with the Jagannathan lab at Stanford University, we (Midhuna and Adam) explored how repeated malaria infections reshape the transcriptional regulation through the epigenome and function of Vδ2+ T cells.

Vδ2+ T cells help fight malaria through inflammatory and cytotoxic responses, but in children who have had malaria many times these cells respond less strongly. We profiled Vδ2+ T cells from Ugandan children, comparing cohorts with high and low transmission and following children over time as transmission dropped, using paired bulk ATAC-seq and RNA-seq as well as CITE-seq. Higher malaria exposure was linked to lower TNF and IFNγ production and to thousands of differentially accessible chromatin regions, with immunoregulatory genes such as LYN, PLCG2 and HAVCR2 (Tim-3) gaining accessibility and pro-inflammatory genes and AP-1 motifs losing it. In an in vitro model, repeated stimulation reproduced this hyporesponsive state, which the tyrosine kinase inhibitor dasatinib partially reversed, pointing to possible ways to restore the function of these cells.

We thank first author Kathleen D. Press and all co-authors, especially Prasanna Jagannathan (Stanford University), who led the study. We are also grateful to our collaboration partners in the labs of William Greenleaf and Sandy Klemm. Above all, we thank the children and families who took part in the cohort studies.

Read the full preprint on bioRxiv: https://doi.org/10.64898/2026.10.02.755737

We are excited to share our new preprint introducing methylTFR, an R package that infers transcription factor (TF) activity from DNA methylation.

DNA methylation shapes where TFs bind and is an important part of gene regulation, but it is hard to analyze at the level of single loci, especially in sparse low-input or single-cell data. methylTFR fixes this by combining methylation signals across all binding sites of a given TF, which gives a low-dimensional and interpretable TF activity profile for each sample. Across 147 human immune cell methylomes, methylTFR identified cell-type-specific regulators, such as CEBP and ETS family factors in myeloid cells. It also traced the naive-to-memory trajectory of CD4+ T cells and pointed to AP-1 factors as key memory regulators. Applied to sparse single-cell methylomes, the TF activity scores can be combined with gene expression and chromatin accessibility in joint factor models, giving multimodal views of lineage regulators.

This work was led by Irem B. Gündüz, together with Regina Nitsch and Sarath Kumar Murugan. We thank Jörn Walter and the members of the Integrative Cellular Biology and Bioinformatics group for their helpful feedback. The single-cell use case builds on data from our earlier collaboration with the Greenleaf and Ecker labs, and the bulk analyses use public data from the BLUEPRINT project. The work was funded by the ERA-NET TRANSCAN-3 project EPILUNAR (01KT2409) and a NanoBioMed Young Investigator Grant from Saarland University.

methylTFR is available on GitHub, with documentation and vignettes at https://epigenomeinformatics.github.io/methylTFR/.

Read the full preprint on bioRxiv: https://doi.org/10.64898/2026.09.29.755279

Together with the Greenleaf and Ecker labs, we characterize the multimodal epigenome and regulatory dynamics in human immune cells in response to pathogen exposure.

Abstract:
Pathogen and chemical exposures lead to profound remodeling of the gene-regulatory landscape across human immune cell populations. Exposure-induced epigenetic signatures in cell states can provide insights into gene regulation driven by these cell-extrinsic stimuli. Here, we present a single-nucleus chromatin accessibility atlas of human immune cells of individuals exposed to HIV, COVID-19, Influenza, organophosphates as well as healthy controls. This atlas comprises 271,299 cells and 319,420 candidate regulatory elements that exhibited dynamic accessibility associated with gene regulation across immune cell states. Our longitudinal HIV cohort revealed epigenetic signatures of T cell exhaustion, manifested in changes in the accessibility of binding sites for the FOXP transcription factor family. We further identified changes in the accessibility of candidate regulatory elements in CD14 monocytes upon SARS-CoV-2 exposure that are associated with a switch in NF-κB to AP-1-based regulation of cytokine networks. By integrating single-cell profiles of DNA methylation from matched samples, we create a multimodal epigenome atlas of human immune cells across various exposure states using the accessibility-derived candidate regulatory elements. Both modalities reveal complementary epigenetic signatures at transcription factor binding sites associated with cell state, as exemplified in the process of memory formation in T-cells. Finally, by linking potentially regulatory DNA methylation signatures to changes in chromatin in monocytes, we identify AP1 motifs exhibiting epigenetic dynamics, indicating selective remodeling in TF networks in cases of severe COVID-19.

Read more:
https://doi.org/10.1101/2025.09.09.675101

We will be teaching workshop (special lecture in bioinformatics (5 CPs)) on the practical analysis of epigenome data. WIn this workshop you will gather hands-on exprience in the analysis of sequencing data for profiling gene expression, DNA methylation, histone modifications and chromatin accessibility. More details can be found on the lecture website.

We will be teaching a special lecture in bioinformatics (9 CPs) on the hot topic of computational methods for single-cell analyses. We will be covering methods and topics from the fields of single-cell transcriptomics, genomics, and epigenomics. Together with the Thomas Hentrich and Fabian Kern we are offering the lecture “Single-cell Bioinformatics”. More details can be found on the lecture website.