小柯机器人

美国哈佛医学院Luca Pinello团队近期取得重要工作进展，他们研究开发了Dictys，这是一种动态基因调控网络，可以利用单细胞多组学剖析发育连续体。相关研究成果2023年8月3日在线发表于《自然—方法学》杂志上。

据介绍，基因调控网络（GRN）是细胞功能和身份的关键决定因素，在发育和疾病过程中会动态地重新连接。尽管经过了数十年的发展，但GRN推理仍然面临挑战，包括动态重新布线、因果推理、反馈回路建模和上下文特异性。

为了应对这些挑战，研究人员开发了Dictys，这是一种动态GRN推断和分析方法，利用染色质可及性和基因表达的多组单细胞分析、上下文特异性转录因子足迹、随机过程网络和单细胞RNA测序读取计数的有效概率建模。Dictys提高了GRN重建的准确性和再现性，并能够在发展背景下对特定背景和动态GRN进行推断和比较分析。Dictys的网络分析通过细胞类型特异性和动态GRN恢复了对人类血液和小鼠皮肤发育的独特见解。它的动态网络可视化能够实现对发育驱动转录因子及其调控靶点的时间分辨发现和研究。

Dictys是一个免费的、开源的、用户友好的Python包。

附：英文原文

Title: Dictys: dynamic gene regulatory network dissects developmental continuum with single-cell multiomics

Author: Wang, Lingfei, Trasanidis, Nikolaos, Wu, Ting, Dong, Guanlan, Hu, Michael, Bauer, Daniel E., Pinello, Luca

Issue&Volume: 2023-08-03

Abstract: Gene regulatory networks (GRNs) are key determinants of cell function and identity and are dynamically rewired during development and disease. Despite decades of advancement, challenges remain in GRN inference, including dynamic rewiring, causal inference, feedback loop modeling and context specificity. To address these challenges, we develop Dictys, a dynamic GRN inference and analysis method that leverages multiomic single-cell assays of chromatin accessibility and gene expression, context-specific transcription factor footprinting, stochastic process network and efficient probabilistic modeling of single-cell RNA-sequencing read counts. Dictys improves GRN reconstruction accuracy and reproducibility and enables the inference and comparative analysis of context-specific and dynamic GRNs across developmental contexts. Dictys’ network analyses recover unique insights in human blood and mouse skin development with cell-type-specific and dynamic GRNs. Its dynamic network visualizations enable time-resolved discovery and investigation of developmental driver transcription factors and their regulated targets. Dictys is available as a free, open-source and user-friendly Python package.

DOI: 10.1038/s41592-023-01971-3

Source: https://www.nature.com/articles/s41592-023-01971-3

Nature Methods：《自然—方法学》，创刊于2004年。隶属于施普林格·自然出版集团，最新IF：47.99
官方网址：https://www.nature.com/nmeth/
投稿链接：https://mts-nmeth.nature.com/cgi-bin/main.plex