دورية أكاديمية
Time varying causal network reconstruction of a mouse cell cycle
| العنوان: | Time varying causal network reconstruction of a mouse cell cycle |
|---|---|
| المؤلفون: | Maryam Masnadi-Shirazi, Mano R. Maurya, Gerald Pao, Eugene Ke, Inder M. Verma, Shankar Subramaniam |
| المصدر: | BMC Bioinformatics, Vol 20, Iss 1, Pp 1-22 (2019) |
| بيانات النشر: | BMC, 2019. |
| سنة النشر: | 2019 |
| المجموعة: | LCC:Computer applications to medicine. Medical informatics LCC:Biology (General) |
| مصطلحات موضوعية: | Dynamics, Cell cycle, Time series, Change point detection, Time varying network reconstruction, Causal inference, Computer applications to medicine. Medical informatics, R858-859.7, Biology (General), QH301-705.5 |
| الوصف: | Abstract Background Biochemical networks are often described through static or time-averaged measurements of the component macromolecules. Temporal variation in these components plays an important role in both describing the dynamical nature of the network as well as providing insights into causal mechanisms. Few methods exist, specifically for systems with many variables, for analyzing time series data to identify distinct temporal regimes and the corresponding time-varying causal networks and mechanisms. Results In this study, we use well-constructed temporal transcriptional measurements in a mammalian cell during a cell cycle, to identify dynamical networks and mechanisms describing the cell cycle. The methods we have used and developed in part deal with Granger causality, Vector Autoregression, Estimation Stability with Cross Validation and a nonparametric change point detection algorithm that enable estimating temporally evolving directed networks that provide a comprehensive picture of the crosstalk among different molecular components. We applied our approach to RNA-seq time-course data spanning nearly two cell cycles from Mouse Embryonic Fibroblast (MEF) primary cells. The change-point detection algorithm is able to extract precise information on the duration and timing of cell cycle phases. Using Least Absolute Shrinkage and Selection Operator (LASSO) and Estimation Stability with Cross Validation (ES-CV), we were able to, without any prior biological knowledge, extract information on the phase-specific causal interaction of cell cycle genes, as well as temporal interdependencies of biological mechanisms through a complete cell cycle. Conclusions The temporal dependence of cellular components we provide in our model goes beyond what is known in the literature. Furthermore, our inference of dynamic interplay of multiple intracellular mechanisms and their temporal dependence on one another can be used to predict time-varying cellular responses, and provide insight on the design of precise experiments for modulating the regulation of the cell cycle. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1471-2105 |
| العلاقة: | http://link.springer.com/article/10.1186/s12859-019-2895-1Test; https://doaj.org/toc/1471-2105Test |
| DOI: | 10.1186/s12859-019-2895-1 |
| الوصول الحر: | https://doaj.org/article/6656d2fa22484971984d6cbe1ecc0746Test |
| رقم الانضمام: | edsdoj.6656d2fa22484971984d6cbe1ecc0746 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 14712105 |
|---|---|
| DOI: | 10.1186/s12859-019-2895-1 |