Biology subjects

Laufer, L.

Publications and source records attributed to Laufer, L..

3 recordsLinked to original sources

bioRxiv2025

Integrated flexible DNA methylation-chromatin segmentation modelingenhances epigenomic state annotation

DNA methylation and histone modifications together shape the cell-type-specific epigenomic landscape. To enable a more comprehensive genome-wide annotation, we developed EpiSegMixMeth (ESMM), the first truly integrative segmentation model combining chromatin marks and DNA methylation. ESMM extends hidden Markov models with flexible read count distributions and state duration modeling. Applied to 154 high-quality human epigenomes from the IHEC EpiAtlas, ESMM substantially improves the annotation of broad heterochromatic regions-covering over 60% of the genome, that are frequently missed by chromatin-only models. Additionally, it precisely defines the boundaries of narrow regulatory elements and resolves local chromatin state transitions during cell differentiation. Notably, we demonstrate that DNA methylation can substitute for missing repressive histone marks in segmentation, ensuring robust annotation across diverse cell types. In memory B-cell development, ESMM reveals fine-scale chromatin state shifts that align with 3D genome architecture changes. Our results highlight the power of integrating DNA methylation into genome segmentation and provide a valuable resource for dissecting cell-type-specific epigenomic regulation.

bioinformatics↗

bioRxiv2024

Neurodegeneration impairs the consolidation of developmentally synchronized behavioral patterns

Animals generate predictable patterns of behavior that are robustly synchronized with the developmental clock. However, the dynamics of the long-term establishment of synchronized behaviors across the entire developmental trajectory, and the neuronal circuits that control this developmental synchronization, remain underexplored. Here, we show that in C. elegans individuals, developmental synchronization of behavior continuously consolidates throughout development time, and that this consolidation is controlled by multiple neuronal pathways. In particular, we found that the degeneration of a specific mechanosensory circuit early in development strongly impairs the developmental synchronization of behavior. Furthermore, early neuronal activity patterns in downstream motor neurons are altered following the mechanosensory circuit degeneration. Interestingly, we show that either pharmacological or genetic neuroprotection of the mechanosensory circuit from degeneration restores normal modes of developmentally synchronized behaviors. These results imply the control of time-locked behaviors across the developmental trajectory by a localized sensory circuit within the nervous system.

neuroscience↗

bioRxiv2023

EpiSegMix: A Flexible Distribution Hidden Markov Model with Duration Modeling for Chromatin State Discovery

MotivationAutomated chromatin segmentation based on ChIP-seq data reveals insights into the epigenetic regulation of chromatin accessibility. Existing segmentation methods are constrained by simplifying modeling assumptions, which may have a negative impact on the segmentation quality. ResultsWe introduce EpiSegMix, a novel segmentation method based on a hidden Markov model with flexible read count distribution types and state duration modeling, allowing for a more flexible modeling of both histone signals and segment lengths. In a comparison with two existing tools, ChromHMM, Segway and EpiCSeg, we show that EpiSegMix is more predictive of cell biology, such as gene expression. Its flexible framework enables it to fit an accurate probabilistic model, which has the potential to increase the biological interpretability of chromatin states. Availability and implementationSource code: https://gitlab.com/rahmannlab/episegmix.

bioinformatics↗