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检索条件"任意字段=第五届全国生物信息学与系统生物学学术大会暨国际生物信息学前沿研讨会高通量时代的生物信息学与系统生物学"

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MicroRNA and transcription factor co-regulatory network analysis reveals miR-19 inhibits CYLD in T-cell acute lymphoblastic leukemia

MicroRNA and transcription factor co-regulatory network anal...

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第五届全国生物信息学与系统生物学学术大会暨国际生物信息学前沿研讨会高通量时代的生物信息学与系统生物学

作者： Huashan Ye Xiaowen Liu Meng Lv Yuliang Wu Shuzhcn Kuang Jing Gong Jun Sun Zhichao Chen An-Yuan Guo Hubei Bioinformatics & Molecular Imaging Key Laboratory Department of Systems BiologyCollege of Life Science and TechnologyHuazhong University of Science and Technology Department of Biochemistry and Molecular Biology TongJi Medical CollegeHuazhong University of Science and Technology Institute of Hematology Union HospitalTongJi Medical CollegeHuazhong University of Science and Technology

Background:T-cell acute lymphoblastic leukemia(T-ALL) is an aggressive hematological malignancy,understanding of its gene expression regulation and molecular mechanisms still remain ***(miRNAs) and transcription factors(TFs) were found to play an important role in the etiology of tumor,and several miRNA-TF mediated regulatory modules have been *** hypothesized that miRNAs and TFs might play combinatory regulatory roles for the diseased genes and,thus,explored miRNA-TF regulatory networks in T-cell acute lymphoblastic leukemia. Methods:Started from experimentally verified T-ALL related miRNAs and genes, we obtained 120 feed-forward loops(FFLs) among T-ALL related genes,miRNAs and TFs through combining target ***,a T-ALL miRNA and TF co-regulatory network was constructed and its significance was tested by statistical methods. Results:Four miRNAs in the miR-17～92 cluster and 4 important genes(CYLD, HOXA9,BCL2L11,and RUNX1) were found as hubs in the ***,we found that miR-19 was highly expressed in T-ALL patients and cell *** expression of miR-19 repress CYLD expression,while miR-19 inhibitor treatment induce CYLD protein expression and decreases NF-κB expression in the downstream signaling ***,miR- 19,CYLD and NF-κB form a regulatory feed-forward loop,which provides new clues for sustained activation of NF-κB in T-ALL. Conclusions:Taken together,we provided the first miRNA-TF co-regulatory network in T-ALL and proposed a model to demonstrate the roles of miR-19 and CYLD in the T-cell *** study may provide potential therapeutic targets for T-ALL and shed light on combining bioinformatics with experiments in the research of complex diseases.

关键词： Feed-forward loop MicroRNA Regulatory network T-ALL Transcription factor

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Predicting bone metastasis of breast cancer using context-specific miRNA regulation modules

Predicting bone metastasis of breast cancer using context-sp...

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第五届全国生物信息学与系统生物学学术大会暨国际生物信息学前沿研讨会高通量时代的生物信息学与系统生物学

作者： Xionghui Zhou Fengji Liang Juan Liu Yinghui Li Shanguang Chen Jianghui Xiong School of Computer Science Wuhan University Bioinformatics Group and Data Coordination Center State Key Lab of Space Medicine Fundamentals and Application(SMFA)China Astronaut Research and Training Center(ACC) School of Computer Science Wuhan University.WuhanChina

Background:The bone is the most frequent target of metastatic breast ***, the underlying molecular mechanisms are *** many microarray studies have reported gene signatures that can predict metastasis in breast cancer,predicting cancer metastasis to a specific organ,such as to bone,remains a challenge in cancer study. Methods:Previously we proposed a concept CoMi(Context Specific miRNA activity), which could quantify the regulation activity of miRNA on specific context(CoMi activity) by calculating the statistical difference of the expression level between the miRNA targets and non-targets in a given context(GO term biological process),and demonstrated its application on predicting *** we extend this concept to CoMi module and use it to predict whether the cancer will metastasize to ***,CoMi features which are significant associated with the bone metastasis are identified by Cox proportional hazards regression. Based on the significant CoMi features,miRNAs regulate on the same context are regarded as a significant miRNA regulation *** each significant CoMi module is used to predict bone metastasis of breast cancer patients by sum up all the risk scores(Cox proportional hazards regression) of CoMi features in the module. Results:We tested the proposed method on a breast cancer cohort contain 855 samples' gene expression profiles together with bone metastasis *** bone metastasis specific CoMi modules are identified,such as module 'hemopoiesis',which has a log rank p value of 9.05e-07 in train dataset,0.0075 in test dataset and 0.0031 in independent test dataset. Considering the hematopoietic stem cell niche is a potential therapeutic target for bone metastatic tumors,our results might facilitate to identify the miRNAs regulation modules involved in hematopoietic stem cell niche. Conclusions:We proposed the concept of CoMi activity module,and identified some CoMi activity modules which could predict bone metas

关键词： Context specific miRNA activity metastasis organ prediction miRNA regulation network

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Investigation of codon usage bias in human tissue-specific genes

Investigation of codon usage bias in human tissue-specific g...

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第五届全国生物信息学与系统生物学学术大会暨国际生物信息学前沿研讨会高通量时代的生物信息学与系统生物学

作者： Lina Ma Peng Cui Jiang Zhu Zhang Zhang CAS Key Laboratory of Genome Sciences and Information Beijing Institute of GenomicsChinese Academy of Sciences Division of Chemical and Life Sciences & Engineering King Abdullah University of Science and TechnologyThuwal 23955-6900Kingdom of Saudi Arabia Department of Pathology Massachusetts General Hospital and Harvard Medical SchoolBostonMassachusettsUSA CAS Key Laboratory of Genome Sciences and Information Beijing Institute of GenomiesChinese Academy of Sciences

Background:Codon usage bias(CUB),a balanced result of mutation and selection,is of great significance in better understanding gene evolution and providing insights on gene function and ***,quantitative comparative analysis of CUB in different human tissues remains unexplored,primarily limited by the comprehensiveness and accuracy of tissue expression data and the reliability of CUB estimation. Methods:Equipped with our newly-developed algorithm(Codon Deviation Coefficient) for accurate estimation of CUB,we performed a systematic investigation on CUB in 10 human tissues based on RNA-Seq data including testis,brain,adipose,breast,colon,heart, kidney,liver,lymph node and muscle. Results:We found that tissue-specific(TS) genes and housekeeping(HK) genes exhibit different CUB *** TS genes across 10 tissues show relatively lower CUBs than HK *** 10 tissues,brain-specific genes have lowest CUBs,whereas adipose-specific genes have highest *** the distribution of CUB,testis-specific genes show the broadest range of CUB,probably due to their large diversity of gene ***, liver-specific genes present the narrowest range of CUB,which may be related to their function exclusively responsible for *** addition,HK genes that are highly and consistently expressed in different tissues have a close correlation between CUB and gene expression level,whereas TS genes do not present such correlation. Conclusions:These results indicate that CUB is a fundamental mechanism in regulating gene expression in both prokaryotes and *** there are multiple mechanisms complicating gene regulation in human,genes that perform basic functions may still be substantially regulated through CUB.

关键词： Codon usage bias(CUB) Codon deviation coefficient(CDC) Tissue-specific genes(TS genes) Housekeeping genes(HK genes)

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Classification of HCV NS5B Polymerase Inhibitors Using Support Vector Machine

Classification of HCV NS5B Polymerase Inhibitors Using Suppo...

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第五届全国生物信息学与系统生物学学术大会暨国际生物信息学前沿研讨会高通量时代的生物信息学与系统生物学

作者： Maolin Wang Changyuan Yu Aixia Yan State Key Laboratory of Chemical Resource Engineering Department of Pharmaceutical EngineeringP.O.Box 53Beijing University of Chemical Technology

Hepatitis C virus(HCV) infection constitutes a global health problem,which affects more than 170 million *** is an enveloped single strand RNA virus and encodes a polyprotein chain of about 3000 amino acids,which is processed into structural and nonstructural (NS) *** processing by viral and cellular host factors results in four structural proteins(Core,E1,E2,p7) and six nonstructural(NS2,NS3,NS4A,NS4B, NS5A,NS5B) ***5B is a RNA-dependent RNA polymerase(RdRp) at the core of the HCV replicative *** the essential role of this enzyme in viral replication, it is anticipated that agents capable of disrupting its function will prove efficacious in the treatment of HCV *** work built several computational models for classification the bioactivity of HCV NS5B Polymerase inhibitors. Using a support vector machine(SVM),three classification models were built to predict whether a compound is an active or weakly active inhibitor based on a dataset of 386 hepatitis C virus(HCV) NS5B polymerase NNIs(non-nucleoside analogue inhibitors) fitting into the pocket of the NNIⅢbinding *** each molecule,global descriptors,2D and 3D property autocorrelation descriptors were calculated from the program ***. Three models were developed with the combination of different types of *** 2 based on 16 global and 2D autocorrelation descriptors gave the highest prediction accuracy of 88.24%and MCC(Matthews correlation coefficient) of 0.789 on test *** 1 based on 13 global descriptors showed the highest prediction accuracy of 86.25%and MCC of 0.732 on external test set(including 80 compounds).Some molecular properties such as molecular shape descriptors(InertiaZ,InertiaX and Span),number of rotatable bonds(NRotBond),water solubility(LogS),and hydrogen bonding related descriptors performed important roles in the interactions between the ligand and NS5B polymerase.

关键词： hepatitis C virus(HCV) NS5B polymerase inhibitor Classification models Support Vector Machine(SVM)

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Preliminary analysis of inflammatory mediator network for prognosis in non-small cell lung cancer(NSCLC) patients receiving chemotherapy

Preliminary analysis of inflammatory mediator network for pr...

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第五届全国生物信息学与系统生物学学术大会暨国际生物信息学前沿研讨会高通量时代的生物信息学与系统生物学

作者： Tao Zeng Dawei Yang Xiangdong Wang ChunxucBai Luonan Chen Key Laboratory of Systems Biology SIBS-Novo Nordisk Translational Research Centre for PreDiabetesShanghai Institutes for Biological SciencesChinese Academy of Sciences Department of Respiratory Medicine Zhongshan Hospital Fudan University Shanghai Institute of Respiratory Disease

Background:Inflammation plays an important role in lung cancer development and cancer *** identify potential protein markers for prognosis in non-small cell lung cancer(NSCLC) patients receiving chemotherapy,the association network of lung cancer relevant inflammatory mediators arc used to study inflammation system responsive to chemotherapy in cancer. Methods:To prepare the data for our study,sera of healthy non-smokers and patients with NSCLC were collected at the first hospital admission for diagnosis,and again at the second and third admission following one and two course of *** to protein concentrations measured in multiplexed cytokine immunoassays,different associations between inflammatory mediators and NSCLC were investigated by computational analysis: the potential markers(cytokines,inflammatory mediators) related to adenocarcinoma and squamous cell carcinoma were identified through feature selection method(SVM-RFE) with 10 cross-validation;the decision trees based on those markers were built to give more readable rules associating to relevant cytokines and cancer types;furthermore,the inferred co-expressed protein interaction network of those protein markers were used to distinguish patients before and after one and two course of chemotherapy. Results:Based on general statistic analysis,several inflammatory mediators were found to be significantly related to NSCLC,and the relation between NSCLC and the combination of inflammatory mediators were further *** sets of cytokines prefer to identify adenocarcinoma / squamous cell carcinoma samples from pool of patients *** decision trees based on these two kinds of markers can both achieve about 80%accuracy in leave-one-out cross-validation,so that they would be confident to use to diagnose new NSCLC *** more interesting and important thing is that,the co-expressed protein interaction network(CEPIN) of cytokines related to adenocarcinoma show dynamic co

关键词： Inflammatory mediator network Prognosis Non-small cell lung cancer Chemotherapy

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In silico cancer drug screening based on microRNAs regulationnetworks

In silico cancer drug screening based on microRNAs regulatio...

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第五届全国生物信息学与系统生物学学术大会暨国际生物信息学前沿研讨会高通量时代的生物信息学与系统生物学

作者： Lida Zhu Fengji Liang Juan Liu Yinghui Li Jianghui Xiong Computer School Wuhan University Bioinformatics Group and Data Coordination Center State Key Lab of Space Medicine Fundamentals and Application(SMFA)China Astronaut Research and Training Center(ACC) Computer School Wuhan UniversityChina

Background:Severalstudies,such as the Connectivity Map(CMAP),showed that gene expression profiles could reflect drug perturbationeffects,and can be used in drug screening and drug *** we introduced a concept CoMi(Context-Specific miRNA Activity),and provide a novel perspective on drug mechanisms of *** this work,we intend to construct a virtual drug screening system and test whether CoMi could be used to capture the common features of approved cancer drugs and discriminate them from other candidate chemicals. Methods & Results:(l)We used correlation analysisby integrating the drugsensitive data(GI50) with gene expression datafrom diverse cancer cell lines in NCI60 datasets,and generated the drug sensitivity gene *** calculating the overlap rate between the drug sensitivity gene sets with disregulated gene set in breast cancer,we defined a drug-disease association index andgenerated a pool of 445 breast cancer associated compounds,including 61 positive drugs(approved breast cancer drugs) and 384 negative drugs.(2)Using the most significant differential CoMi features in positive *** drugs,a NaiveBayesian classifier could accurately predict the successful breast cancer drugs(AUC 0.86),and its performance was significantly exceed the mRNA signature based drug screening system (AUC 0.75),far superior to naive CMAP screening system(AUC0.56).(3)Further analysis of the network consisted of CoMi with good classification performance,highlighted some high connected miRNA nodes,including important cancer-related miRNAs(mir-495) and tumor suppressormiRNA(mir-520d);In addition,a number of high connectivity functional gene setsare also closely related with the biological processes of cancer(for example,cell differentiation).(4)Integrating differential expressed CoMi induced by Paclitaxel with breast cancer specific CoMi,weexaminedits application on classifying drug responsiveness in a breast cancer cohort using paclitaxel as neoadjuvant thera

关键词： microRNAs In silico cancer drug screening based on microRNAs regulationnetworks

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Chromatin Organization in Regulating Alternative Splicing

Chromatin Organization in Regulating Alternative Splicing

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第五届全国生物信息学与系统生物学学术大会暨国际生物信息学前沿研讨会高通量时代的生物信息学与系统生物学

作者： Huan Huang Xiao Sun State Key Laboratory of Bioelectronics Southeast University

Background:In the human genome,alternative splicing is a versatile mechanism to regulat gene expression at the level of precursor mRNA(pre-mRNA) ***, increasingly researches showed that pre-mRNA splicing is not an isolated process;rather it is coupled with transcription and a role of this coupling is in alternative splicing regulation. Furthermore,nucleosome positioning and histone modification plays an important role in cross-talk between transcription and mRNA *** researches indicate that nucleosome positioning and histone modification may influence inclusion of internal exon sequences. Methods:Alternative exons were classified using the Astalavista framework and the Human Reference genome exons(hg18 database,UCSC genome browser)(Foissac & Sammeth 2007).However,as the data sets were incomplete,only 2117 skipped exons,391 retained introns,648 alternative acceptors,and 618 alternative donors were obtained.A total of 115,618 constitutive exons were retrieved using unique internal reference sequence(RefSeq) exons(hgl8,UCSC),removing alternative exons which include alternative events of UCSC and alternative events acquired by using the Astalavista framework with the Human Reference genome exons and mRNA exons. A genome-wide map of nucleosome positions in resting human CD4+ T cells(Schones et al.2008),Granulocytes and vitro was used(Sidow et al.2011).The genome-wide distribution of 37 histone methylations and histone acetylations as well as histone variant H2A.Z in human CD4+T cells was also used(Barski et al.2007;Wang et al.2008). Results:Nucleosomes are preferentially positioned within constitutive exons and/or constitutive portions of alternative exons.H2AZ,H3K4mme3 and some histone acetylations (H2BK120ac,H3K9ac,H3K18ac,H3K27ac,H4K91ac,et al) have an important role in regulating alternative donors. Conclusions:Well positioned nucleosome may serve as "speed bump" for RNAPII to facilitate recruiting splicing factors to the pre-mRNA to improve

关键词： nucleosome occupancy histone modification alternative splicing

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Conservation and Divergence of DNA Methylation Patterns among Multiple Tissues/Cells in Human and Mouse

Conservation and Divergence of DNA Methylation Patterns amon...

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第五届全国生物信息学与系统生物学学术大会暨国际生物信息学前沿研讨会高通量时代的生物信息学与系统生物学

作者：侯光远 Tiantian Gu Qiong Wu School of Life Science and Biotechnology Harbin Institute of Technology

Background:DNA methylation has been regarded as essential epigenetic mechanism involved in gene expression in specific spatiotemporal ***-wide CpG islands (CGIs) and gene promoter regions methylation profiles have been described in numbers of tissues and cells among different ***,the inter-tissues and inter-species DNA methylation pattern and function in other genome regions are not yet *** this end,we systematically analyzed the methylation difference in genome-wide CpG-sites location within seven genome categories(Up2kb,5'-UTR,CodingExon,Intron,3'-UTR,Down2kb and Intergenic regions) across multiple tissues in human and mouse. Methods:We collected methylation data in the human and mouse ES cells,B cells, fibroblast,brain,liver and lung samples detected by RRBS provided by Meissner A et al. QDMR,a bioinformatic tool based on Shannon entropy,was utilized to quantify and identify methylation differences across these tissues and cells in both ***,we analyzed the functions of genes related with methylation differences within seven genome region categories by functional annotation tools in the DAVID Bioinformatics Resources 6.7 website. Results:We found that most CpG-sites located in CGIs,Up2kb,5'-UTR and Intron regions in the both species are *** Person Correlation Coefficient(PCC) analysis exhibited that genome-wild DNA methylation profile is significantly conserved across 6 different tissues and cells from the same species(0.806

关键词： DNA methylation Conservation Evolution Differentially methylated CpG sites Methylation difference

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Bioinformatics analysis and functional verification of the polymorphisms in 3' Untranslated Regulatory Region of DLX3 gene in Chinese Merino

Bioinformatics analysis and functional verification of the p...

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第五届全国生物信息学与系统生物学学术大会暨国际生物信息学前沿研讨会高通量时代的生物信息学与系统生物学

作者： Enguang Rong Lei Yu Zhiwei Zhang Shupei Qiao Hua Yang Hui Li NingWang Key Laboratory of Chicken Genetics and Breeding Ministry of Agriculture College of Animal Science and Technology Northeast Agricultural University Institute of Animal Husbandry and Veterinary Xinjiang Academy of Agriculture and Reclamation Science

Backgroud:The Distal-less 3（DLX3） is a Distal-less homeodomain protein that belongs to the members of the DLX vertebrate ***3 acts as a transcriptional activator and plays a critical role in the development of hair follicle and hair ***,the four SNPs in 3'UTR of sheep DLX3 gene and their haplotypes had consistently significant effect on wool curvature ***,luciferase reporter assay indicated that these four SNPs all have a functional role for the expression of DLX3 gene. Methods:The objective of this study was to deeply explore the effect mechanisms of the four SNPs in 3'UTR of sheep DLX3 *** online bioinformatics software was applied to analyze the sequence structure and motifs in 3'UTR,and the binding change of miRNAs caused by single nucleotide mutation in 3'UTR of sheep DLX3 ***,we used luciferase reporter assay and Real-time PCR to validate the results of bioinformatics prediction. Results:The bioinformatics analysis showed that the SNP function in 3'UTR of the sheep DLX3 gene was mediated by the *** finally confirmed that the miR-204*, miR-491-5p and the miR-188 targeted into the 3'UTR of sheep DLX3 gene,and the regulation of these miRNAs were affected by the SNP c.*118T>C,c.*228T>C,c.*1038039 insl, *** the mRNA expression level of DLX3 gene and its target genes downstream were changed for these miRNAs regulation. Conclusions:All the four SNPs in 3'UTR of sheep DLX3 gene were functional sites, and they played roles via regulation of miRNA at *** current study laid the foundation for the probe into the correlation between the polymorphisms in 3'UTR of sheep DLX3 gene and wool curvature trait.

关键词： sheep DLX3 gene 3'UTR luciferase reporter assay miRNA

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Emergence of a New HIV-1 CRFO1AE Variant in Guangxi,Southern China

Emergence of a New HIV-1 CRFO1AE Variant in Guangxi,Southern...

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第五届全国生物信息学与系统生物学学术大会暨国际生物信息学前沿研讨会高通量时代的生物信息学与系统生物学

作者： Haiyan Zeng Zhiwu Sun Shujia Liang Lingnuo Li Yanyan Jiang Wei Liu Binlian Sun Jingyun Li Rongge Yang Research Group of HIV Molecular Epidemiology and Virology The State Key Laboratory of VirologyWuhan Institution of VirologyChinese Academy of Sciences Guangxi Province Center for Disease Prevention and Control NanningGuangxi 530028The People's Republic of China Department of AIDS Research The State Key Laboratory of Pathogen and BiosecurityBeijing Institute of Microbiology and Epidemiology

Background:Recent years' reports in Guangxi showed that CRFO1AE had dominated in the central city Nanning and the eastern city Liuzhou,and there may be more than one introductions of CRF01E in *** gain a deeper understanding on the evolution of the HIV-1 epidemic and genetic characterization of CRFO1E in Guangxi,we recruited 349 HIV/AIDS patients from the cities all over Guangxi. Methods:Full-length gag,pol genes and partial env gene were amplified and analyzed using phylogenetic,recombinant,intersubject diversity,signature pattern,and sequence logo approaches. Results:The distribution of HIV-1 genotypes based on gag,pol and partial env sequences（n=349） was as follows:CRFO1E（66.5%）,CRF08BC（19.2%）,CRF07C （7.2%）,URF（4.6%）,subtype B（1.7%）,and subtype B'（0.9%）.CRF01AE predominated in all geographical regions and risk populations and there were multiple introductions of CRF01_ AE strains in *** found a peculiar CRF01E monophyletic lineage distinct from other CRF01E viruses,and we designated it "CRF01E-v" for ***01_ AE-v circulating in both heterosexuals and injecting drug users（IDUs） had accounted for 39.7%) of *** showed a selective advantage in the Guangxi population and formed its own characteristic compared with all the CRF01E references. Conclusions:Our results suggested that CRF01E-v was a new variant of CRF01E and it might lead to a new epidemic in Guangxi.

关键词： HIV-1 CRF01AE China signature pattern CRF0lAE-v

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