scholarly journals Coupled Single-Cell CRISPR Screening and Epigenomic Profiling Reveals Causal Gene Regulatory Networks

Cell ◽  
2019 ◽  
Vol 176 (1-2) ◽  
pp. 361-376.e17 ◽  
Author(s):  
Adam J. Rubin ◽  
Kevin R. Parker ◽  
Ansuman T. Satpathy ◽  
Yanyan Qi ◽  
Beijing Wu ◽  
...  
Cell Systems ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 265-274.e11 ◽  
Author(s):  
Xiaojie Qiu ◽  
Arman Rahimzamani ◽  
Li Wang ◽  
Bingcheng Ren ◽  
Qi Mao ◽  
...  

2018 ◽  
Author(s):  
Xiaojie Qiu ◽  
Arman Rahimzamani ◽  
Li Wang ◽  
Qi Mao ◽  
Timothy Durham ◽  
...  

AbstractSingle-cell transcriptome sequencing now routinely samples thousands of cells, potentially providing enough data to reconstruct causal gene regulatory networks from observational data. Here, we present Scribe, a toolkit for detecting and visualizing causal regulatory interactions between genes and explore the potential for single-cell experiments to power network reconstruction. Scribe employs Restricted Directed Information to determine causality by estimating the strength of information transferred from a potential regulator to its downstream target. We apply Scribe and other leading approaches for causal network reconstruction to several types of single-cell measurements and show that there is a dramatic drop in performance for "pseudotime” ordered single-cell data compared to true time series data. We demonstrate that performing causal inference requires temporal coupling between measurements. We show that methods such as “RNA velocity” restore some degree of coupling through an analysis of chromaffin cell fate commitment. These analyses therefore highlight an important shortcoming in experimental and computational methods for analyzing gene regulation at single-cell resolution and point the way towards overcoming it.


Patterns ◽  
2021 ◽  
Vol 2 (9) ◽  
pp. 100332
Author(s):  
N. Alexia Raharinirina ◽  
Felix Peppert ◽  
Max von Kleist ◽  
Christof Schütte ◽  
Vikram Sunkara

2020 ◽  
Author(s):  
Turki Turki ◽  
Y-h. Taguchi

AbstractAnalyzing single-cell pancreatic data would play an important role in understanding various metabolic diseases and health conditions. Due to the sparsity and noise present in such single-cell gene expression data, analyzing various functions related to the inference of gene regulatory networks, derived from single-cell data, remains difficult, thereby posing a barrier to the deepening of understanding of cellular metabolism. Since recent studies have led to the reliable inference of single-cell gene regulatory networks (SCGRNs), the challenge of discriminating between SCGRNs has now arisen. By accurately discriminating between SCGRNs (e.g., distinguishing SCGRNs of healthy pancreas from those of T2D pancreas), biologists would be able to annotate, organize, visualize, and identify common patterns of SCGRNs for metabolic diseases. Such annotated SCGRNs could play an important role in speeding up the process of building large data repositories. In this study, we aimed to contribute to the development of a novel deep learning (DL) application. First, we generated a dataset consisting of 224 SCGRNs belonging to both T2D and healthy pancreas and made it freely available. Next, we chose seven DL architectures, including VGG16, VGG19, Xception, ResNet50, ResNet101, DenseNet121, and DenseNet169, trained each of them on the dataset, and checked prediction based on a test set. We evaluated the DL architectures on an HP workstation platform with a single NVIDIA GeForce RTX 2080Ti GPU. Experimental results on the whole dataset, using several performance measures, demonstrated the superiority of VGG19 DL model in the automatic classification of SCGRNs, derived from the single-cell pancreatic data.


2018 ◽  
Vol 17 (4) ◽  
pp. 246-254 ◽  
Author(s):  
Mark W E J Fiers ◽  
Liesbeth Minnoye ◽  
Sara Aibar ◽  
Carmen Bravo González-Blas ◽  
Zeynep Kalender Atak ◽  
...  

2017 ◽  
Vol 34 (2) ◽  
pp. 258-266 ◽  
Author(s):  
Nan Papili Gao ◽  
S M Minhaz Ud-Dean ◽  
Olivier Gandrillon ◽  
Rudiyanto Gunawan

2019 ◽  
Author(s):  
Soumya Korrapati ◽  
Ian Taukulis ◽  
Rafal Olszewski ◽  
Madeline Pyle ◽  
Shoujun Gu ◽  
...  

AbstractThe stria vascularis (SV) generates the endocochlear potential (EP) in the inner ear and is necessary for proper hair cell mechanotransduction and hearing. While channels belonging to SV cell types are known to play crucial roles in EP generation, relatively little is known about gene regulatory networks that underlie the ability of the SV to generate and maintain the EP. Using single cell and single nucleus RNA-sequencing, we identify and validate known and rare cell populations in the SV. Furthermore, we establish a basis for understanding molecular mechanisms underlying SV function by identifying potential gene regulatory networks as well as druggable gene targets. Finally, we associate known deafness genes with adult SV cell types. This work establishes a basis for dissecting the genetic mechanisms underlying the role of the SV in hearing and will serve as a basis for designing therapeutic approaches to hearing loss related to SV dysfunction.


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