Modeling of Cellular Systems: Application in Stem Cell Research and Computational Disease Modeling

Book published by Springer International Publishing (2018)

The large-scale development of high-throughput sequencing technologies has allowed the generation of reliable omics data at different regulatory levels. Integrative computational models enable the ... [more ▼]

The large-scale development of high-throughput sequencing technologies has allowed the generation of reliable omics data at different regulatory levels. Integrative computational models enable the disentangling of a complex interplay between these interconnected levels of regulation by interpreting these large quantities of biomedical information in a systematic way. In the context of human diseases, network modeling of complex gene-gene interactions has been successfully used for understanding disease-related dysregulations and for predicting novel drug targets to revert the diseased phenotype. Furthermore, these computational network models have emerged as a promising tool to dissect the mechanisms of developmental processes such as cellular differentiation, transdifferentiation, and reprogramming. In this chapter, we provide an overview of recent advances in the field of computational modeling of cellular systems and known limitations. A particular attention is paid to highlight the impact of computational modeling on our understanding of stem cell biology and the complex multifactorial nature of human diseases and their treatment. [less ▲]

Integrative Computational Network Analysis Reveals Site-Specific Mediators of Inflammation in Alzheimer's Disease

in Frontiers in Physiology (2018)

A complex of the ubiquitin ligase TRIM32 and the deubiquitinase USP7 balances the level of c-Myc ubiquitination and thereby determines neural stem cell fate specification

in Cell Death and Differentiation (2018)

Signaling-Dependent Control of Apical Membrane Size and Self-Renewal in Rosette-Stage Human Neuroepithelial Stem Cells

in Stem Cell Reports (2018)

Single-cell gene expression analysis reveals regulators of distinct cell subpopulations among developing human neurons

in Genome Research (2017)

Prediction of Chromatin Accessibility in Gene-Regulatory Regions from Transcriptomics Data

in Scientific Reports (2017)

Bioinformatics Tools for Genome-Wide Epigenetic Research

in Neuroepigenomics in Aging and Disease (2017)

RefBool: a reference-based algorithm for discretizing gene expression data

in Bioinformatics (2017)

Identifying niche mediated regulatory factors of stem cell phenotypic state: a systems biology approach

in FEBS Letters (2017)

A systems biology approach to identify niche determinants of cellular phenotypes

in Stem Cell Research (2016)

Recent reports indicate a dominant role for cellular microenvironment or niche for stably maintaining cellular phenotypic states. Identification of key niche mediated signaling that maintains stem cells ... [more ▼]

Recent reports indicate a dominant role for cellular microenvironment or niche for stably maintaining cellular phenotypic states. Identification of key niche mediated signaling that maintains stem cells in specific phenotypic states remains a challenge, mainly due to the complex and dynamic nature of stem cell-niche interactions. In order to overcome this, we consider that stem cells maintain their phenotypic state by experiencing a constant effect created by the niche by integrating its signals via signaling pathways. Such a constant niche effect should induce sustained activation/inhibition of specific stem cell signaling pathways that controls the gene regulatory program defining the cellular phenotypic state. Based on this view, we propose a computational approach to identify the most likely receptor mediated signaling responsible for transmitting niche signals to the transcriptional regulatory network that maintain cell-specific gene expression patterns, termed as niche determinants. We demonstrate the utility of our method in different stem cell systems by identifying several known and novel niche determinants. Given the key role of niche in several degenerative diseases, identification of niche determinants can aid in developing strategies for potential applications in regenerative medicine. [less ▲]