bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2020.07.29.226498

Estimation of Three-Dimensional Chromatin Morphology for Nuclear Classification and Characterisation

Rana, P.·Sowmya, A.·Meijering, E.·Song, Y.
View original source ↗Export metadata ↓

Abstract

Classification and characterisation of cellular morphological states are vital for understanding cell differentiation, development, proliferation and diverse pathological conditions. As the onset of morphological changes transpires following genetic alterations in the chromatin configuration inside the nucleus, the nuclear texture as one of the low-level properties if detected and quantified accurately has the potential to provide insights on nuclear organisation and enable early diagnosis and prognosis. This study presents a three dimensional (3D) nuclear texture description method for cell nucleus classification and variation measurement in chromatin patterns on the transition to another phenotypic state. The proposed approach includes third plane information using hyperplanes into the design of the Sorted Random Projections (SRP) texture feature. The significance of including third plane information for low-resolution volumetric images is investigated by comparing the performance of 3D texture descriptor with its respective pseudo 3D form that ignores the interslice intensity correlations. Following classification, changes in chromatin pattern are estimated by computing the ratio of heterochromatin and euchromatin corresponding to their respective intensities and image gradient obtained by 3D SRP. The proposed method is evaluated on two publicly available 3D image datasets of human fibroblast and human prostate cancer cell lines in two phenotypic states obtained from the public Statistics Online Computational Resource. Experimental results show that 3D SRP and 3D Local Binary Pattern provide better results than other utilised handcrafted descriptors and deep learning features extracted using a pre-trained model. The results also show the advantage of utilising 3D feature descriptor for classification over its corresponding pseudo version. In addition, the proposed method validates that as the cell passes to another phenotypic state, there is a change in intensity and aggregation of heterochromatin. Author SummaryAutomated classification and measurement of cellular phenotypic traits can significantly impact clinical decision making. Early detection of diseases requires an accurate description of low-level cellular features to detect small-scale abnormalities in the few abnormal cells in the tissue microenvironment. The challenge is the development of a computational approach for 3D textural feature description that can capture the heterogeneous information in multiple dimensions and characterise the cells in their ultimate and intermediate phenotypic states effectively. Our work has proposed the method and metrics to measure chromatin condensation pattern and classify the phenotypic states. Experimental evaluation on the 3D image set of human fibroblast and human prostate cancer cell collections validates the proposed method for the classification of cell states. Results also signify the credibility of proposed metrics to characterise the cellular phenotypic states and contributes to studies related to early diagnosis, prognosis and drug resistance.

Source connections

Explore related subjects

bioinformaticsPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Rana, P., Sowmya, A., Meijering, E., Song, Y.. 2020-07-29. Estimation of Three-Dimensional Chromatin Morphology for Nuclear Classification and Characterisation. https://doi.org/10.1101/2020.07.29.226498

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

spatialMET: an open and scalable framework for spatial metabolomics analysis

Mass spectrometry imaging (MSI) enables spatially resolved metabolomics in intact tissue sections, but analysis remains challenging at scale. Existing MSI workflows often require users to combine multiple software tools, while others rely on proprietary vendor software that limits interoperability and reproducibility. To address these challenges, we developed spatialMET, an open-source framework that provides an end-to-end workflow for MSI analysis. spatialMET provides a unified platform for preprocessing, spatial domain detection, and visualization. Downstream analyses include differential abundance testing, spatial autocorrelation and gradient analysis, dimensionality reduction, and correlation network analysis. Spatial domain detection uses hcdist, a C-based hierarchical clustering implementation that substantially reduces runtime and memory use relative to existing R-based approaches. spatialMET can be run through an interactive R Shiny application or as a standalone command-line workflow for larger datasets or high-performance computing environments. Applied to mouse small cell lung cancer MALDI-MSI data containing 284,673 pixels, spatialMET identified tumor-associated, stromal, and adjacent lung spatial domains that aligned with matched histology. Differential abundance analysis identified 117 m/z features that differed between tumor and stromal regions, while spatial autocorrelation analyses revealed spatially structured abundance patterns. Applying spatialMET to mouse lung adenocarcinoma data from an entire lung lobe containing 338,477 pixels further demonstrated scalability and captured spatial heterogeneity across tumor and surrounding lung tissue. In summary, spatialMET provides a scalable, open-source framework for end-to-end spatial metabolomics analysis, and it is distributed as a Docker container for reproducible deployment. Source code and installation instructions are available at https://github.com/biodatalab/spatialMET.

bioinformatics↗
bioRxiv2026

Probing the transcriptome response to shivering in skeletal muscle using a multilayered bioinformatics approach

Cold acclimation holds therapeutic potential for improving metabolic health. We previously demonstrated that repeated cold-induced shivering enhances insulin sensitivity in humans. However, the molecular pathways that underlie the skeletal muscle shivering response, and how these relate to beneficial physiological effects, remain poorly understood. In this study, we combined complementary bioinformatics approaches to allow in-depth analysis of the transcriptomic response of human skeletal muscle to repeated shivering. We identified a robust transcriptional signature and show a sex-specific component in the shivering skeletal muscle response, which seemed to diminish following cold adaptation. Our findings provide mechanistic insights into cold-induced muscle adaptations, shed light on potential interesting molecular targets for further investigation, and emphasize the importance of including both sexes in future cold acclimation studies.

bioinformatics↗
bioRxiv2026

An Information Geometry approach to model topological trajectories and Gene Expression Radius from UMAP geometry.

Understanding the relationship between gene expression dynamics and cellular identity remains a central challenge in single cell biology. Here, we introduce a novel computational and mathematical framework that integrates information geometry, fuzzy topology, and UMAP analysis to model gene expression landscapes derived from single cell RNA sequencing data. We formalize gene expression data as a fuzzy topological space, where interactions between expression points are governed by probabilistic distributions inspired by manifold learning approaches such as UMAP. Within this framework, we define an information geometric structure through a Fisher metric induced by these distributions, enabling the computation of geodesic trajectories that capture cellular differentiation processes. A key contribution of this work is the derivation of analytical conditions, expressed as expression radius formulas, that characterize local neighborhoods in gene expression space. These conditions allow for the identification of genes associated with stem cell states and predictions in transitional cell types in future work. Application of the proposed framework to single cell datasets reveals biologically meaningful gene sets enriched in key regulatory pathways and transcription factors, demonstrating the capacity of our approach to uncover latent structure in complex gene expression data. Our results suggest that integrating differential geometry with statistical learning theory offers a powerful paradigm for modeling genotype and phenotype relationships and cellular state transitions, with potential implications for precision medicine and systems biology.

bioinformatics↗