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Computational evidence of A-to-I RNA editing in nucleus transcriptome of Arabidopsis thaliana

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Frontiers of Electrical and Electronic Engineering in China 2009年第4期4卷 349-361页

作者： Pufeng DU Yang CHEN Yanda LI MOE Key laboratory of bioinformatics and bioinformatics Division TNLIST/Department of AutomationTsinghua UniversityBeijing 100084China

RNA editing is a mechanism that can increase the complexity of the transcriptome via the insertion,deletion,or substitution of single or multiple nucleotides of mRNA *** the last two decades,A-to-I RNA editing,which is catalyzed by the ADAR family enzymes,was discovered in many metazoans.C-to-U and U-to-C RNA editing were found in the mitochondria and plastids of ***,there is no report about RNA editing in plant nucleus transcriptome ***,by integrating resources from public databases with computational methods,this paper proposes that A-to-I RNA editing mechanism may exist in the nucleus of Arabidopsis *** characteristics of the potential A-to-I RNA editing sites in Arabidopsis thaliana are similar to those we have known in animals.

关键词： RNA editing nucleus Arabidopsis thaliana

Evidence for association of multi-exon skipping events with tumors

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Frontiers of Electrical and Electronic Engineering in China 2008年第3期3卷 260-266页

作者： Jianning BI Tao PENG Yanda LI MOE Key laboratory of bioinformatics and bioinformatics Div TNLIST/Department of AutomationTsinghua UniversityBeijing 100084China

Alternative splicing(AS)has been shown to be frequently present in human ***,it has been observed in some experimental studies thatmulti-exon skipping(MES)events often appear in tumorous *** by this observation,we conducted a genome-wide analysis of MES events to investigate their association with *** results show that MES events are more likely associated with tumors than single-exon skipping(SES)and the degree of association increases with the num-ber of skipped ***,MES events are found to be less conserved than their SES counterparts,which provides additional evidence for our results because dis-ease-associated AS events should be eliminated during ***,these differences still existed even after comparison of MES and SES events with similar-length skipped *** results demonstrate that MES events may be associated with tumors and suggest that MES isoforms might be useful in cancer diagnosis.

关键词： multi-exon skipping event single-exon skip-ping event tumor

CGPS:A machine learning-based approach integrating multiple gene set analysis tools for better prioritization of biologically relevant pathways

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Journal of Genetics and Genomics 2018年第9期45卷 489-504页

作者： Chen Ai Lei Kong Center for bioinformatics State Key Laboratory of Protein and Plant Gene ResearchSchool of Life SciencesPeking University

Gene set enrichment（GSE） analyses play an important role in the interpretation of large-scale transcriptome datasets. Multiple GSE tools can be integrated into a single method as obtaining optimal results is challenging due to the plethora of GSE tools and their discrepant performances. Several existing ensemble methods lead to different scores in sorting pathways as integrated results; furthermore, it is difficult for users to choose a single ensemble score to obtain optimal final results. Here, we develop an ensemble method using a machine learning approach called Combined Gene set analysis incorporating Prioritization and Sensitivity（CGPS） that integrates the results provided by nine prominent GSE tools into a single ensemble score（R score） to sort pathways as integrated results. Moreover, to the best of our knowledge, CGPS is the first GSE ensemble method built based on a priori knowledge of pathways and phenotypes. Compared with 10 widely used individual methods and five types of ensemble scores from two ensemble methods, we demonstrate that sorting pathways based on the R score can better prioritize relevant pathways, as established by an evaluation of 120 simulated datasets and 45 real ***, CGPS is applied to expression data involving the drug panobinostat, which is an anticancer treatment against multiple myeloma. The results identify cell processes associated with cancer, such as the p53 signaling pathway（hsa04115）; by contrast, according to two ensemble methods（EnrichmentBrowser and EGSEA）, this pathway has a rank higher than 20, which may cause users to miss the pathway in their analyses. We show that this method, which is based on a priori knowledge, can capture valuable biological information from numerous types of gene set collections, such as KEGG pathways, GO terms, Reactome, and BioCarta. CGPS is publicly available as a standalone source code at ftp：//***/pub/CGPS_download/***.

关键词： Gene expression Differential expression Gene set enrichment Support vector machine

Single-cell Transcriptomes Reveal Characteristics of MicroRNAs in Gene Expression Noise Reduction

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Genomics, Proteomics & bioinformatics 2021年第3期19卷 394-407页

作者： Tao Hu Lei Wei Shuailin Li Tianrun Cheng Xuegong Zhang Xiaowo Wang Ministry of Education Key laboratory of bioinformatics Center for Synthetic and Systems BiologyBioinformatics DivisionBeijing National Research Center for Information Science and TechnologyDepartment of AutomationTsinghua UniversityBeijing 100084China

Isogenic cells growing in identical environments show cell-to-cell variations because of the stochasticity in gene *** levels of variation or noise can disrupt robust gene expression and result in tremendous consequences for cell *** this work,we showed evidence from single-cell RNA sequencing data analysis that microRNAs(miRNAs)can reduce gene expression noise at the mRNA level in mouse *** identified that the miRNA expression level,number of targets,target pool abundance,and miRNA-target interaction strength are the key features contributing to noise *** tend to work together in cooperative subnetworks to repress target noise synergistically in a cell type-specific *** building a physical model of post-transcriptional regulation and observing in synthetic gene circuits,we demonstrated that accelerated degradation with elevated transcriptional activation of the miRNA target provides resistance to extrinsic ***,through the integrated analysis of single-cell RNA and miRNA expression profiles,we demonstrated that miRNAs are important post-transcriptional regulators for reducing gene expression noise and conferring robustness to biological processes.

关键词： MicroRNA regulation Gene expression noise Competing RNA microRNA regulation network Singlecell RNA sequencing

Co-regulated gene module detection for time series gene expression data

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Frontiers of Electrical and Electronic Engineering in China 2012年第4期7卷 357-366页

作者： Wanwan TANG Rui LI Shao LI Yanda LI MOE Key laboratory of bioinformatics Bioinformatics DivisionTsinghua National Laboratory of Information Science and Technology /Department of Automation Tsinghua University Beijing 100084 China

It is important to detect interaction effect of multiple genes during certain biological process. In this paper, we proposed, from systems biology perspective, the concept of co-regulated gene module, which consists of genes that are regulated by the same regulator（s）. Given a time series gene expression data, a hidden Markov model-based Bayesian model was developed to calculate the likelihood of the observed data, assuming the co-regulated gene modules are known. We further developed a Gibbs sampling strategy that is integrated with reversible jump Markov chain Monte Carlo to obtain the posterior probabilities of the co-regulated gene modules. Simulation study validated the proposed method. When compared with two existing methods, the proposed approach significantly outperformed the conventional methods.

关键词： co-regulated gene module Bayesian hiddenMarkov model Markov chain Monte Carlo

A quantitative understanding of microRNA- mediated competing endogenous RNA regulation

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Frontiers of Electrical and Electronic Engineering in China 2016年第1期4卷 47-57页

作者： Ye Yuan Xinying Ren Zhen Xie Xiaowo Wang Ministry of Education Key laboratory of bioinformatics and bioinformatics Division Center for Synthetic and Systems BiologyTsinghua National Laboratory for Information Science and Technology/Department of Automation Tsinghua University Beijing100084 China

MicroRNA （miRNA） plays key roles in post-transcriptional regulations. Recently, a competing endogenous RNA （ceRNA） hypothesis has been proposed that miRNA targets could communicate and regulate each other through titrating shared miRNAs, which provides a new layer of gene regulation. Though a number of ceRNAs playing biological functions have been identified, the ceRNA hypothesis remains controversial. Recent experimental and theoretical studies argued that the modulation of a single RNA species could hardly change the expression level of competing miRNA targets through ceRNA effect under normal physiological conditions. Here, we reviewed a common framework to model miRNA regulations, and summarized the current theoretical and experimental studies for quantitative understanding ceRNA effect. By revisiting a coarse-grained ceRNA model, we proposed that network topology could significantly influence the competing effect and ceRNA regulation at protein level could be much stronger than that at RNA level. We also provided a conditional independent binding equation to describe miRNA relative repression on different target, which could be applied to quantify siRNA off-target effect.

关键词： microRNA regulation competing endogenous RNA molecular titration quantitative model complexnetworks

A Differential Evolution Approach for Protein Folding Using a Lattice Model

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Journal of Computer Science & Technology 2007年第6期22卷 904-908页

作者： Heitor Silverio Lopes Reginaldo Bitello bioinformatics laboratory Federal University of Technology-ParanáAv.7 de setembro3165 80230-901 CuritibaBrazil

Protein folding is a relevant computational problem in bioinformatics, for which many heuristic algorithms have been proposed. This work presents a methodology for the application of differential evolution （DE） to the problem of protein folding, using the bi-dimensional hydrophobic-polar model. DE is a relatively recent evolutionary algorithm, and has been used successfully in several engineering optimization problems, usually with continuous variables. We introduce the concept of genotype-phenotype mapping in DE in order to provide a mapping between the real-valued vector and an actual folding. The methodology is detailed and several experiments with benchmarks are done. We compared the results with other similar implementations. The proposed DE has shown to be competitive, statistically consistent and very promising.

关键词： bioinformatics differential evolution evolutionary computation protein folding

Observations on potential novel transcripts from RNA-Seq data

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Frontiers of Electrical and Electronic Engineering in China 2011年第2期6卷 275-282页

作者： Chao YE Linxi LIU Xi WANG Xuegong ZHANG Key laboratory of bioinformatics and bioinformatics Division Ministry of EducationTsinghua National Laboratory for Information Science and Technology/Department of AutomationTsinghua UniversityBeijing 100084China

With the rapid development of next generation deep sequencing technologies,sequencing cDNA reverse-transcribed from RNA molecules(RNA-Seq)has become a key approach in studying gene expression and *** RNA-Seq does not rely on annotation of known genes,it provides the opportunity of discovering transcripts that have not been annotated in current *** the distribution of RNASeq signals and a systematic view on the potential new transcripts revealed from the signals is an important step toward the understanding of transcriptomes.

关键词： RNA-Seq novel transcripts next generation sequencing bioinformatics

Large-scale study of long non-coding RNA functions based on structure and expression features

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Science China(Life Sciences) 2013年第10期56卷 953-959页

作者： ZHAO Yi WANG Jian CHEN XiaoWei LUO HaiTao ZHAO YunJie XIAO Yi CHEN RenSheng bioinformatics Research Group Advanced Computing Research LaboratoryInstitute of Computing TechnologyChinese Academy ofSciences Department of Physics Huazhong University of Science and Technology laboratory of bioinformatics and Non-coding RNA Institute of BiophysicsChinese Academy of Sciences

Mammals and other complex organisms can transcribe an abundance of long non-coding RNAs(lncRNAs)that fulfill a wide variety of regulatory roles in many biological *** roles,including as scaffolds and as guides for protein-coding genes,mainly depend on the structure and expression level of *** this review,we focus on the current methods for analyzing lncRNA structure and expression,which is basic but necessary information for in-depth,large-scale analysis of lncRNA functions.

关键词： non-coding RNA structure expression function