用RNA-seq数据的新联合模型对差异表达的异构体进行贝叶斯式鉴定
1Bradley Department of Electrical and Computer Engineering, Virginia Polytechnic Institute and State University, Arlington, Virginia, United Sates of America.
PLoS computational biology
|January 31, 2025
概括
贝叶斯Iso是一种新的贝叶斯方法,通过建模异型变异性来识别RNA-seq数据中的差异基因表达. 这种方法有助于了解乳腺癌复发途径,并确定关键生物标志物.
科学领域:
- 生物信息学是一种生物信息学.
- 计算生物学 计算生物学
- 基因组学就是基因组学.
背景情况:
- RNA测序 (RNA-seq) 能够进行转录基因分析.
- 识别差异表达的异构体对于理解基因调节至关重要.
- 现有的方法可能无法完全捕捉异形变异性和差异表达.
研究的目的:
- 开发一个贝叶斯方法,BayesIso,用于从RNA-seq数据中识别差异表达的异构.
- 使用联合模型模拟样本变异性和差异化异形态状态.
- 将贝叶斯Iso应用于乳腺癌数据,以发现复发相关的途径.
主要方法:
- 开发了BayesIso,这是一个贝叶斯的方法来进行异型分析.
- 利用了一种新的联合模型,将Poisson-Lognormal和Gamma-Gamma模型纳入可变性.
- 采用马尔科夫链蒙特卡洛 (MCMC) 来共同估计异形状态和模型参数.
- 使用模拟和真实RNA-seq数据验证,包括乳腺癌样本.
主要成果:
- 贝叶斯Iso有效地检测出差异表达的异构体,特别是具有多个异构体的基因.
- 对乳腺癌数据的应用确定了与复发相关的关键异构体和途径.
- 包括PI3K/AKT/mTOR,PTEN,Jak-STAT,MAPK和Wnt在内的信号通路与乳腺癌的发展和复发有关.
- 在早期复发瘤中观察到代谢和细胞周期基因 (例如CD36,TOP2A) 的上调和免疫反应基因 (例如NFATC1) 的下调.
结论:
- 贝叶斯还为异形水平的微分表达式分析提供了一个强大的框架.
- 该研究强调了与乳腺癌复发相关的特定信号通路和分子特征.
- 确定了早期乳腺癌复发的潜在生物标志物,为治疗策略提供了洞察力.
相关概念视频
Ribosome Profiling
3.5K
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...
3.5K
RNA-seq
9.8K
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...
9.8K
Experimental RNAi
6.0K
RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
6.0K
One-Compartment Open Model: Wagner-Nelson and Loo Riegelman Method for ka Estimation
371
This lesson introduces two critical methods in pharmacokinetics, the Wagner-Nelson and Loo-Riegelman methods, used for estimating the absorption rate constant (ka) for drugs administered via non-intravenous routes. The Wagner-Nelson method relates ka to the plasma concentration derived from the slope of a semilog percent unabsorbed time plot. However, it is limited to drugs with one-compartment kinetics and can be impacted by factors like gastrointestinal motility or enzymatic degradation.
On...
On...
371
Alternative RNA Splicing
20.9K
Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
20.9K
Regulation of Expression at Multiple Steps
864
The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
864


