Construction of Discrete Model of Human Pluripotency in Predicting Lineage-Specific Outcomes and Targeted Knockdowns of Essential Genes
| Autor: | Romasha Gupta, Priyanka Narad, Abhishek Sengupta, Lakshay Anand |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Pluripotent Stem Cells
0301 basic medicine Computer science In silico Human Embryonic Stem Cells lcsh:Medicine Computational biology Network topology Article 03 medical and health sciences Humans lcsh:Science Induced pluripotent stem cell Gene Embryonic Stem Cells Network model Multidisciplinary Mechanism (biology) Gene Expression Profiling lcsh:R Cell Differentiation Initial topology Embryonic stem cell 030104 developmental biology Boolean network lcsh:Q Octamer Transcription Factor-3 |
| Zdroj: | Scientific Reports, Vol 8, Iss 1, Pp 1-10 (2018) Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-018-29480-w |
| Popis: | A network consisting of 45 core genes was developed for the genes/proteins responsible for loss/gain of function in human pluripotent stem cells. The nodes were included on the basis of literature curation. The initial network topology was further refined by constructing an inferred Boolean model from time-series RNA-seq expression data. The final Boolean network was obtained by integration of the initial topology and the inferred topology into a refined model termed as the integrated model. Expression levels were observed to be bi-modular for most of the genes involved in the mechanism of human pluripotency. Thus, single and combinatorial perturbations/knockdowns were executed using an in silico approach. The model perturbations were validated with literature studies. A number of outcomes are predicted using the knockdowns of the core pluripotency circuit and we are able to establish the minimum requirement for maintenance of pluripotency in human. The network model is able to predict lineage-specific outcomes and targeted knockdowns of essential genes involved in human pluripotency which are challenging to perform due to ethical constraints surrounding human embryonic stem cells. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|