scholarly journals Model-Based Deconvolution of Cell Cycle Time-Series Data Reveals Gene Expression Details at High Resolution

2009 ◽  
Vol 5 (8) ◽  
pp. e1000460 ◽  
Author(s):  
Dan Siegal-Gaskins ◽  
Joshua N. Ash ◽  
Sean Crosson
2017 ◽  
Author(s):  
Anthony Szedlak ◽  
Spencer Sims ◽  
Nicholas Smith ◽  
Giovanni Paternostro ◽  
Carlo Piermarocchi

AbstractModern time series gene expression and other omics data sets have enabled unprecedented resolution of the dynamics of cellular processes such as cell cycle and response to pharmaceutical compounds. In anticipation of the proliferation of time series data sets in the near future, we use the Hopfield model, a recurrent neural network based on spin glasses, to model the dynamics of cell cycle in HeLa (human cervical cancer) and S. cerevisiae cells. We study some of the rich dynamical properties of these cyclic Hopfield systems, including the ability of populations of simulated cells to recreate experimental expression data and the effects of noise on the dynamics. Next, we use a genetic algorithm to identify sets of genes which, when selectively inhibited by local external fields representing gene silencing compounds such as kinase inhibitors, disrupt the encoded cell cycle. We find, for example, that inhibiting the set of four kinases BRD4, MAPK1, NEK7, and YES1 in HeLa cells causes simulated cells to accumulate in the M phase. Finally, we suggest possible improvements and extensions to our model.Author SummaryCell cycle – the process in which a parent cell replicates its DNA and divides into two daughter cells – is an upregulated process in many forms of cancer. Identifying gene inhibition targets to regulate cell cycle is important to the development of effective therapies. Although modern high throughput techniques offer unprecedented resolution of the molecular details of biological processes like cell cycle, analyzing the vast quantities of the resulting experimental data and extracting actionable information remains a formidable task. Here, we create a dynamical model of the process of cell cycle using the Hopfield model (a type of recurrent neural network) and gene expression data from human cervical cancer cells and yeast cells. We find that the model recreates the oscillations observed in experimental data. Tuning the level of noise (representing the inherent randomness in gene expression and regulation) to the “edge of chaos” is crucial for the proper behavior of the system. We then use this model to identify potential gene targets for disrupting the process of cell cycle. This method could be applied to other time series data sets and used to predict the effects of untested targeted perturbations.


2017 ◽  
Vol 13 (11) ◽  
pp. e1005849 ◽  
Author(s):  
Anthony Szedlak ◽  
Spencer Sims ◽  
Nicholas Smith ◽  
Giovanni Paternostro ◽  
Carlo Piermarocchi

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Hitoshi Iuchi ◽  
Michiaki Hamada

Abstract Time-course experiments using parallel sequencers have the potential to uncover gradual changes in cells over time that cannot be observed in a two-point comparison. An essential step in time-series data analysis is the identification of temporal differentially expressed genes (TEGs) under two conditions (e.g. control versus case). Model-based approaches, which are typical TEG detection methods, often set one parameter (e.g. degree or degree of freedom) for one dataset. This approach risks modeling of linearly increasing genes with higher-order functions, or fitting of cyclic gene expression with linear functions, thereby leading to false positives/negatives. Here, we present a Jonckheere–Terpstra–Kendall (JTK)-based non-parametric algorithm for TEG detection. Benchmarks, using simulation data, show that the JTK-based approach outperforms existing methods, especially in long time-series experiments. Additionally, application of JTK in the analysis of time-series RNA-seq data from seven tissue types, across developmental stages in mouse and rat, suggested that the wave pattern contributes to the TEG identification of JTK, not the difference in expression levels. This result suggests that JTK is a suitable algorithm when focusing on expression patterns over time rather than expression levels, such as comparisons between different species. These results show that JTK is an excellent candidate for TEG detection.


2020 ◽  
Vol 12 (19) ◽  
pp. 3120
Author(s):  
Luojia Hu ◽  
Nan Xu ◽  
Jian Liang ◽  
Zhichao Li ◽  
Luzhen Chen ◽  
...  

A high resolution mangrove map (e.g., 10-m), including mangrove patches with small size, is urgently needed for mangrove protection and ecosystem function estimation, because more small mangrove patches have disappeared with influence of human disturbance and sea-level rise. However, recent national-scale mangrove forest maps are mainly derived from 30-m Landsat imagery, and their spatial resolution is relatively coarse to accurately characterize the extent of mangroves, especially those with small size. Now, Sentinel imagery with 10-m resolution provides an opportunity for generating high-resolution mangrove maps containing these small mangrove patches. Here, we used spectral/backscatter-temporal variability metrics (quantiles) derived from Sentinel-1 SAR (Synthetic Aperture Radar) and/or Sentinel-2 MSI (Multispectral Instrument) time-series imagery as input features of random forest to classify mangroves in China. We found that Sentinel-2 (F1-Score of 0.895) is more effective than Sentinel-1 (F1-score of 0.88) in mangrove extraction, and a combination of SAR and MSI imagery can get the best accuracy (F1-score of 0.94). The 10-m mangrove map was derived by combining SAR and MSI data, which identified 20003 ha mangroves in China, and the area of small mangrove patches (<1 ha) is 1741 ha, occupying 8.7% of the whole mangrove area. At the province level, Guangdong has the largest area (819 ha) of small mangrove patches, and in Fujian, the percentage of small mangrove patches is the highest (11.4%). A comparison with existing 30-m mangrove products showed noticeable disagreement, indicating the necessity for generating mangrove extent product with 10-m resolution. This study demonstrates the significant potential of using Sentinel-1 and Sentinel-2 images to produce an accurate and high-resolution mangrove forest map with Google Earth Engine (GEE). The mangrove forest map is expected to provide critical information to conservation managers, scientists, and other stakeholders in monitoring the dynamics of the mangrove forest.


2020 ◽  
Vol 27 (1) ◽  
Author(s):  
E Afrifa‐Yamoah ◽  
U. A. Mueller ◽  
S. M. Taylor ◽  
A. J. Fisher

2020 ◽  
Vol 36 (19) ◽  
pp. 4885-4893 ◽  
Author(s):  
Baoshan Ma ◽  
Mingkun Fang ◽  
Xiangtian Jiao

Abstract Motivation Gene regulatory networks (GRNs) capture the regulatory interactions between genes, resulting from the fundamental biological process of transcription and translation. In some cases, the topology of GRNs is not known, and has to be inferred from gene expression data. Most of the existing GRNs reconstruction algorithms are either applied to time-series data or steady-state data. Although time-series data include more information about the system dynamics, steady-state data imply stability of the underlying regulatory networks. Results In this article, we propose a method for inferring GRNs from time-series and steady-state data jointly. We make use of a non-linear ordinary differential equations framework to model dynamic gene regulation and an importance measurement strategy to infer all putative regulatory links efficiently. The proposed method is evaluated extensively on the artificial DREAM4 dataset and two real gene expression datasets of yeast and Escherichia coli. Based on public benchmark datasets, the proposed method outperforms other popular inference algorithms in terms of overall score. By comparing the performance on the datasets with different scales, the results show that our method still keeps good robustness and accuracy at a low computational complexity. Availability and implementation The proposed method is written in the Python language, and is available at: https://github.com/lab319/GRNs_nonlinear_ODEs Supplementary information Supplementary data are available at Bioinformatics online.


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