分类: 生物学 >> 生物物理学 >> 生物物理、生物化学与分子生物学 提交时间: 2016-05-12
摘要: With the rapid development of high-throughput sequencing technologies, the emerging of methylated RNA immunoprecipitation sequencing (MeRIP-seq) technology makes it possible to detect RNA epigenetic modifications in a large scale, which allows transcriptome-wide profiling of RNA methylation. Mining the patterns of global mRNA methylation from these MeRIP-seq data can help reveal the potential functional roles of these mRNA methylations in regulating gene expression, splicing, RNA editing and RNA stability, effectively guiding the therapeutic intervention of cancer. Here, the principle of MeRIP-seq sequencing was first introduced. Then, the recent progress of the processing and analysis of MeRIP-seq data were comprehensively discussed. In the end, the computational problems and challenges faced in the process of MeRIP-seq data processing were also summarized.
分类: 生物学 >> 生物物理学 >> 生物物理、生物化学与分子生物学 提交时间: 2016-05-11
摘要: Biochemical modifications to mRNA, especially N6-methyladenosine (m(6)A) and 5-methylcytosine (m(5)C), have been recently shown to be associated with crucial biological functions. Despite the intriguing advancements, little is known so far about the dynamic landscape of RNA methylome across different cell types and how the epitranscriptome is regulated at the system level by enzymes, i.e., RNA methyltransferases and demethylases. To investigate this issue, a meta-analysis of m(6)A MeRIP-Seq datasets collected from 10 different experimental conditions (cell type/tissue or treatment) is performed, and the combinatorial epitranscriptome, which consists of 42758 m(6)A sites, is extracted and divided into 3 clusters, in which the methylation sites are likely to be hyper- or hypo-methylated simultaneously (or co-methylated), indicating the sharing of a common methylation regulator. Four different clustering approaches are used, including K-means, hierarchical clustering (HC), Bayesian factor regression model (BFRM) and nonnegative matrix factorization (NMF) to unveil the co-methylation patterns. To validate whether the patterns are corresponding to enzymatic regulators, i.e., RNA methyltransferases or demethylases, the target sites of a known m(6)A regulator, fat mass and obesity-associated protein (FTO), are identified from an independent mouse MeRIP-Seq dataset and lifted to human. Our study shows that 3 out of the 4 clustering approaches used can successfully identify a group of methylation sites overlapping with FTO target sites at a significance level of 0.05 (after multiple hypothesis adjustment), among which, the result of NMF is the most significant (p-value 2.81 x 10(-06)). We defined a new approach evaluating the consistency between two clustering results which shows that clustering results of different methods are highly correlated strongly indicating the existence of co-methylation patterns. Consistent with recent studies, a number of cancer and neuronal disease-related bimolecular functions are enriched in the identified clusters, which are biological functions that can be regulated at the epitranscriptional level, indicating the pharmaceutical prospect of RNA N6-methyladenosine-related studies. This result successfully reveals the linkage between the global RNA co-methylation patterns embedded in the epitranscriptomic data under multiple experimental conditions and the latent enzymatic regulators, suggesting a promising direction towards a more comprehensive understanding of the epitranscriptome.
分类: 物理学 >> 核物理学 提交时间: 2025-04-17
摘要: Metal foil element furnaces are widely used in neutron scattering sample environments. However, since the metal foil blocks the neutron beam, these furnaces typically have a large background from the metal foil. Therefore, we designed a special heating element with an innovative perforated structure for the furnace. This novel heating element can significantly reduce the instrumental background, and is specifically applicable to the Multi-Physics Instrument and High-Pressure Neutron Diffractometer in CSNS. This structure reduces material obstruction of the neutron beam, thereby greatly lowering the experimental background. Additionally, we performed electro-thermal-mechanical coupled finite element simulation on the heating element to analyze its temperature and stress distribution, and identified the locations most susceptible to failure. We adjusted the heating element's hole size to study temperature and stress changes, providing a theoretical basis for future optimization of the heating element. This furnace is extensively applied in CSNS, facilitating users in accomplishing neutron scattering experiments and achieving a series of research outcomes.
分类: 物理学 >> 核物理学 提交时间: 2025-02-27
摘要: The use of automatic sample exchange technology can greatly improve the efficiency of neutron scattering experiments. China spallation neutron source (CSNS) has currently developed a cryogenic sample changer that design for exchange sample in the temperature range of 100K to 300K and finally achieve the minimum operating temperature is 80K. Samples are provided with a temperature ranging from 4.2K to 800K by CCR-02 through a closed cycle refrigerator (CCR) and a heater. This paper introduces the structure of the sample changer, which can accommodate up to 24 samples and the replacement time of each sample does not exceed 2 minutes. CSNS II phase will develop a second generation sample changer with an operating temperature range from 10K to 350K. For this requirement, we researched why the chain drive jammed in 80K and redesigned the chain and the support. By simulating in Ansys Workbench, we concluded that the new chain has more excellent performance in low-temperature and its stress is small and uniform. Because of the stress concentration, the S chain plate with a clamping angle of 20°is selected. The new support under Fluent can get the lowest temperature is 4.48K (316 stainless steel) and 4.23K (titanium). The new design will be tested after processing is completed.