PROFET从scRNA-seq数据中预测连续基因表达动态,以阐明癌症治疗反应的异质性
Yu-Chen Cheng1,2,3,4, Hyemin Gu5, Thomas O McDonald1,2,3,4
1Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA.
bioRxiv : the preprint server for biology
|July 9, 2025
概括
PROFET从静态单细胞RNA测序数据中重建连续基因表达轨迹. 这种计算框架揭示了细胞状态转变和乳腺癌治疗反应的异质性.
科学领域:
- 计算生物学 计算生物学
- 基因组学就是基因组学.
- 系统生物学 系统生物学
背景情况:
- 单细胞RNA测序 (scRNA-seq) 提供了细胞基因表达的高分辨率快照.
- 目前的scRNA-seq方法无法随着时间的推移捕捉连续的基因表达动态.
- 了解动态基因表达对于破译细胞状态转变和对刺激的反应至关重要.
研究的目的:
- 开发一个计算框架,PROFET (基于粒子的生成力匹配表达轨迹的重建),用于从稀疏的scRNA-seq数据重建连续的单细胞基因表达轨迹.
- 应用PROFET来研究乳腺癌中对palbociclib治疗的细胞异质性和动态反应.
主要方法:
- PROFET使用了一种新的利普希茨调节梯度流方法,在时间标记的scRNA-seq样本之间产生粒子流.
- 用神经力匹配来学习轨迹重建的全球向量场.
- 该框架使用合成数据和老鼠/人类体外数据集进行了验证.
主要成果:
- 从静态scRNA-seq数据中,PROFET成功地重建了非线性基因表达轨迹.
- 在乳腺癌中应用到palbociclib治疗中,发现了具有显著表型变化的细胞子群.
- 鉴定了富含于治疗响应子群体的独特表面标记物.
结论:
- PROFET能够从静态数据中推断连续的单细胞表达轨迹.
- 这种计算工具对于在治疗反应期间剖析细胞状态异质性非常有价值.
- PROFET促进了对复杂生物系统中动态细胞过程的理解.
相关概念视频
03:21RNA-seq
10.4K
RNA sequencing, or RNA-Seq, is a high-throughput sequencing technology used to study the transcriptome of a cell. Transcriptomics helps to interpret the functional elements of a genome and identify the molecular constituents of an organism. Additionally, it also helps in understanding the development of an organism and the occurrence of diseases.
Before the discovery of RNA-seq, microarray-based methods and Sanger sequencing were used for transcriptome analysis. However, while...
Before the discovery of RNA-seq, microarray-based methods and Sanger sequencing were used for transcriptome analysis. However, while...
10.4K
02:24Ribosome Profiling
3.6K
Ribosome profiling or ribo-sequencing is a deep sequencing technique that produces a snapshot of active translation in a cell. It selectively sequences the mRNAs protected by ribosomes to get an insight into a cell’s translation landscape at any given point in time.
Applications of ribosome profiling
Ribosome profiling has many applications, including in vivo monitoring of translation inside a particular organ or tissue type and quantifying new protein synthesis levels.
The technique...
Applications of ribosome profiling
Ribosome profiling has many applications, including in vivo monitoring of translation inside a particular organ or tissue type and quantifying new protein synthesis levels.
The technique...
3.6K
01:36What is Gene Expression?
9.2K
A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is comprised of nucleotides and proteins are comprised of amino acids, a mediator is required to convert the information encoded in DNA into proteins. This mediator is the messenger RNA (mRNA). mRNA copies the blueprint from DNA by a process called transcription. In eukaryotes, transcription occurs in the nucleus by complementary base-pairing with the DNA template. The mRNA is then...
9.2K
02:51mRNA Stability and Gene Expression
5.7K
The structure and stability of mRNA molecules regulates gene expression, as mRNAs are a key step in the pathway from gene to protein. In eukaryotes, the half-life of mRNA varies from a few minutes up to several days. mRNA stability is essential in growth and development. The absence of the proteins regulating its stability, such as tristetraprolin in mice, can cause systemic issues, including bone marrow overgrowth, inflammation, and autoimmunity.
Cis-acting Elements involved in mRNA stability
Cis-acting Elements involved in mRNA stability
5.7K