scholarly journals Transcription factor enrichment analysis (TFEA) quantifies the activity of multiple transcription factors from a single experiment

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Jonathan D. Rubin ◽  
Jacob T. Stanley ◽  
Rutendo F. Sigauke ◽  
Cecilia B. Levandowski ◽  
Zachary L. Maas ◽  
...  

AbstractDetecting changes in the activity of a transcription factor (TF) in response to a perturbation provides insights into the underlying cellular process. Transcription Factor Enrichment Analysis (TFEA) is a robust and reliable computational method that detects positional motif enrichment associated with changes in transcription observed in response to a perturbation. TFEA detects positional motif enrichment within a list of ranked regions of interest (ROIs), typically sites of RNA polymerase initiation inferred from regulatory data such as nascent transcription. Therefore, we also introduce muMerge, a statistically principled method of generating a consensus list of ROIs from multiple replicates and conditions. TFEA is broadly applicable to data that informs on transcriptional regulation including nascent transcription (eg. PRO-Seq), CAGE, histone ChIP-Seq, and accessibility data (e.g., ATAC-Seq). TFEA not only identifies the key regulators responding to a perturbation, but also temporally unravels regulatory networks with time series data. Consequently, TFEA serves as a hypothesis-generating tool that provides an easy, rigorous, and cost-effective means to broadly assess TF activity yielding new biological insights.

2020 ◽  
Author(s):  
Jonathan D. Rubin ◽  
Jacob T. Stanley ◽  
Rutendo F. Sigauke ◽  
Cecilia B. Levandowski ◽  
Zachary L. Maas ◽  
...  

1AbstractDetecting differential activation of transcription factors (TFs) in response to perturbation provides insight into cellular processes. Transcription Factor Enrichment Analysis (TFEA) is a robust and reliable computational method that detects differential activity of hundreds of TFs given any set of perturbation data. TFEA draws inspiration from GSEA and detects positional motif enrichment within a list of ranked regions of interest (ROIs). As ROIs are typically inferred from the data, we also introduce muMerge, a statistically principled method of generating a consensus list of ROIs from multiple replicates and conditions. TFEA is broadly applicable to data that informs on transcriptional regulation including nascent (eg. PRO-Seq), CAGE, ChIP-Seq, and accessibility (e.g. ATAC-Seq). TFEA not only identifies the key regulators responding to a perturbation, but also temporally unravels regulatory networks with time series data. Consequently, TFEA serves as a hypothesis-generating tool that provides an easy, rigorous, and cost-effective means to broadly assess TF activity yielding new biological insights.


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.


Entropy ◽  
2020 ◽  
Vol 22 (12) ◽  
pp. 1343 ◽  
Author(s):  
Robin A. Choudhury ◽  
Neil McRoberts

In a previous study, air sampling using vortex air samplers combined with species-specific amplification of pathogen DNA was carried out over two years in four or five locations in the Salinas Valley of California. The resulting time series data for the abundance of pathogen DNA trapped per day displayed complex dynamics with features of both deterministic (chaotic) and stochastic uncertainty. Methods of nonlinear time series analysis developed for the reconstruction of low dimensional attractors provided new insights into the complexity of pathogen abundance data. In particular, the analyses suggested that the length of time series data that it is practical or cost-effective to collect may limit the ability to definitively classify the uncertainty in the data. Over the two years of the study, five location/year combinations were classified as having stochastic linear dynamics and four were not. Calculation of entropy values for either the number of pathogen DNA copies or for a binary string indicating whether the pathogen abundance data were increasing revealed (1) some robust differences in the dynamics between seasons that were not obvious in the time series data themselves and (2) that the series were almost all at their theoretical maximum entropy value when considered from the simple perspective of whether instantaneous change along the sequence was positive.


2015 ◽  
Vol 13 (03) ◽  
pp. 1541006 ◽  
Author(s):  
Asako Komori ◽  
Yukihiro Maki ◽  
Isao Ono ◽  
Masahiro Okamoto

Biological systems are composed of biomolecules such as genes, proteins, metabolites, and signaling components, which interact in complex networks. To understand complex biological systems, it is important to be capable of inferring regulatory networks from experimental time series data. In previous studies, we developed efficient numerical optimization methods for inferring these networks, but we have yet to test the performance of our methods when considering the error (noise) that is inherent in experimental data. In this study, we investigated the noise tolerance of our proposed inferring engine. We prepared the noise data using the Langevin equation, and compared the performance of our method with that of alternative optimization methods.


2021 ◽  
Author(s):  
Romain Bulteau ◽  
Mirko Francesconi

AbstractGenome-wide gene expression profiling is a powerful tool for exploratory analyses, providing a high dimensional picture of the state of a biological system. However, uncontrolled variation among samples can obscure and confound the effect of variables of interest. Uncontrolled developmental variation is often a major source of unknown expression variation in developmental systems. Existing methods to sort samples from transcriptomes require many samples to infer developmental trajectories and only provide a relative pseudo-time.Here we present RAPToR (Real Age Prediction from Transcriptome staging on Reference), a simple computational method to estimate the absolute developmental age of even a single sample from its gene expression with up to minutes precision. We achieve this by staging samples on high-resolution reference developmental expression profiles we build from existing time series data. We implemented RAPToR for the most common animal model systems: nematode, fruit fly, zebrafish, and mouse, and demonstrate application for non-model organisms. We show how developmental variation discovered by RAPToR can be exploited to increase power to detect differential expression and to untangle the signal of perturbations of interest even when it is completely confounded with development. We anticipate our RAPToR post-profiling staging strategy will be especially useful in large scale single organism profiling because it eliminates the need for synchronization or for a tedious and potentially difficult step of accurate staging before profiling.


2019 ◽  
Author(s):  
Pengjia Bao ◽  
Jiayu Luo ◽  
Yanbin Liu ◽  
Min Chu ◽  
Qingmiao Ren ◽  
...  

Abstract Background: Mammalian hair play an important role in mammals' ability to adapt to changing climatic environments. The seasonal circulation of yak hair helps them adapt to high altitude but the regulation mechanisms of the proliferation and differentiation of hair follicle (HF) cells during development are still unknown. Here, using time series data for whole genome expression profiles and hormone contents, we systematically analyzed the mechanism regulating the periodic expression of hair development in the yak and reviewed how different combinations of genetic pathways regulate HF development and cycling. Results: This study used high-throughput RNA sequencing to provide a detailed description of global gene expression in 15 samples from five developmental time points during the yak hair cycle. A total of 11,666 genes were found to be involved in the hair cycle. According to clustering analysis and the morphological features we observed, we found that these 15 samples could be significantly grouped into three phases, which represent different developmental periods in the hair cycle. A total of 2,316 genes were identified in these three consecutive developmental periods and their expression patterns could be divided into 9 clusters; GO annotation and KEGG pathway enrichment were performed on these differentially expressed genes (DEGs), showing that the three periods have distinctive functions in the seasonal hair cycle. The regulatory network of related signaling factors highlighted the interaction and dynamic expression of key DEGs during the seasonal hair cycle. Through co-expression analysis, we revealed a number of modular hub genes highly associated with hormones that may play unique roles in hormonal regulation of events associated with the hair cycle. Conclusions: Our results revealed the molecular mechanisms and developmental regulatory networks of the seasonal hair cycle in the yak and filled a gap in the current research field. The findings will be valuable in further understanding the alpine adaptation mechanism in the yak, which is important in order to make full use of yak hair resources and promote the economic development of pastoral plateau areas. Keywords: Hair cycle, Seasonal development, Transcriptome, Yak


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