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

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.