Biology subjects

Slanina, S.

Publications and source records attributed to Slanina, S..

7 recordsLinked to original sources

bioRxiv2018

Chromosome compartmentalization replacement during stem cell differentiation

In this paper, changes in a large-scale 3D structure of chromosomes during stem cell differentiation is studied. The polymer coarse-grained model of a human interphase chromosome is introduced which reproduces the experimental Hi-C contact maps in chromosomes 12, 17 for both embryonic stem and differentiated cells with high accuracy. Model based analysis of Hi-C data suggests a mechanism of establishment of preferential long-range chromosomal contacts and compartmentalization replacement during cell stem differentiation. The model provides the conceptual basis for integration of data on the dynamics of chromatin interactions, the 3D structure of chromosomes and gene expression during stem cell differentiation or reprogramming.

biophysics↗

bioRxiv2017

Dose response relationships for gamma radiation induced chromosomal instability

Different cell lines demonstrate various dose response for radiation-induced chromosomal instability (RICI). To clarify the origin of differences we analyzed own and published data on RICI for four cell lines, V79, TK6, WTK1 and CHO-K1 on the basis of the mechanistic RICI model. We conclude that observable dose-response shapes, both plateau-like and strong dose dependent behavior, may be jointly explained by the same model of RICI. Mechanistic modeling reveals that a variation of certain set of RICI parameters leads to strong modification of dose-response curve.

cancer biology↗

bioRxiv2017

Quantifying relationships between chromosome organization and chromosomal aberrations

The question of to what extent large scale structure of interphase chromosomes contributes to chromosomal exchange aberrations is discussed for a long time but still remains unclear. We designed the polymer model of 3D organization of a mouse chromosome and simulated X-ray induced chromosomal aberrations exploring two alternative hypotheses: the probability of contacted damaged loci entailing a chromosomal rearrangement is (a) a constant value or (b) not constant, depending on the distribution of DNAsel-hypersensitivity peaks along the chromosome. The latter hypothesis proved to explain the experimental data better than the former, meaning that not only large-scale structure but also local chromatin alterations play a role.

systems biology↗

bioRxiv2017

Quantitative relationships for radiation induced chromosome instability: data analysis

The experimental observations demonstrate that different cell lines reveal various shape of dynamic curves for radiation-induced chromosomal instability (RICI). We analyzed our own and published data on RICI for three cell lines, CHO-K1, V79 and TK6, on the basis of the mechanistic RICI model. We demonstrate that all three dynamic curves can be successfully described by the proposed model with partially cell line specific parameters.

cancer biology↗

bioRxiv2017

DNA Damage Induced Chromosomal Instability. Computational modeling view.

The origin of dose-response curves for radiation-induced chromosomal instability (CI) is studied using the mechanistic CI model. The model takes into account DNA damage generation and repair in the progeny of irradiated cells, cell passage through mitotic cycle, and intercellular signaling. It is shown that the dose-response curves are closely related to the dynamic curves. The principles underlying this relationship are analyzed.

systems biology↗

bioRxiv2016

Physical models of spatial genome organization

Remodeling of nuclear organization occurs during normal cell development, differentiation and cancer. One of the biggest gaps of knowledge remains how to link the information on chromatin and chromosome structural organization with genes activity. In this paper we introduce some physical ideas and a general computational method demonstrating how genome 3D architecture and its remodeling can be quantitatively modeled. We study a hypothetical scenario of alterations of chromosome territories positioning in the course of cell proliferation. On this basis we obtain quantitative information about chromosomal contacts in the nucleus. We predict changes of radial distributions of contacts between chromosomal megabase domains during proliferation. The proposed modeling approach may be helpful in integrating experimental data on nuclear reorganization associated with normal development and with various diseases. This predictive modeling may find applications in genome research of normal and cancer cells, stem cell biology, biology of aging, etc.

cancer biology↗

bioRxiv2016

Chromosome interactome inferred from mitosis-G1 transition

The progress in experimental techniques aimed at 3D genome study is yet to bring about revelation of basic principles of genome folding. Chromosome conformation capture Hi-C technologies provide genome wide mapping of genomic loci interactions but spatial organization of chromosomes remains unknown. Here, we develop a polymer modeling approach to generate the ensemble of 3D chromosome conformations for mapping genetic loci contacts and the positions of megabase chromosomal domains in interphase chromosome at different time of mitosis-interphase transition. We demonstrate that (*) whole chromosome contact map (interactome) generated for mouse chromosome 18 structure and (**) contact patterns, observed soon after mitotic decondensation and remaining similar during G1, correlate well with the experimental Hi-C contact data. The results suggest that contact map formation and spatial compartmentalization of an interphase chromosome are driven by interactions between different types of domains during formation of globular chromosome state at the end of mitotis-G1 transition.

biophysics↗