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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

Computational Identification of 99 Insect MicroRNAs Using Comparative genomics

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Tsinghua Science and Technology 2008年第4期13卷 425-432页

作者：何涛李非古槿李瑞强李飞 bioinformatics Division Tsinghua National Laboratory for Information Science and Technology (TNLIST) Department of Automation Tsinghua University Beijing 100084 China Beijing genomics Institute Chinese Academy of Sciences Beijing 100084 China bioinformatics Division Tsinghua National Laboratory for Information Science and Technology (TNLIST) Department of Automation Tsinghua University Beijing 100084 China Department of Entomology College of Plant Pro-tection Nanjing Agricultural University Nanjing 210095 China

In recent years, much effort has been made in identifying microRNA （miRNA） genes from mammals insects, worms, plants, and viruses. Continuing the search for more miRNA genes is still important but difficult. This paper presents a computational strategy based on comparative genomics analysis. The algorithm was used to scan four invertebrate genomes, Drosophila melangoster, Bombyx mori, Apis mellifera, and Anopheles gambiae, which are either model organisms or medically/economically important insects. 99 new miRNA genes were predicted from the four insect species which can be grouped into 17 miRNA gene families, of which 10 of the miRNA families are insect-specific. Sequence similarity analysis showed that 16 of the newly predicted insect miRNAs belong to the K-box, GY-box, and Brd-box miRNA families which are important participators in Notch-related pathways. To test the validity of the algorithm, 39 predicted insect miRNA genes from D. melangoster and A. mellifera were selected for further biological validation. 34 （87%） predicted miRNA genes＇ transcripts were successfully detected by reverse transcription-polymerase chain reaction experiments. Thus, this strategy can be used to efficiently screen for miRNA genes conserved cross species.

关键词： microRNA (miRNA) insect comparative genomics reverse transcription-polymerase chain reaction

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

Celiac Disease and Elevated Liver Enzymes:A Still Not Fully Defined Pathogenesis

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Journal of Clinical and Translational Hepatology 2021年第2期9卷 274-275页

作者： Linda Beenet Diego Tonesi Department of Pathology&laboratory Medicine University of California Los Angeles(UCLA)Technology Center for Genomics&BioinformaticsLos AngelesCAUSA Gastroenterology and Endoscopy Unit Ospedale Maggiore PoliclinicoMilanItaly

Dear Editor,We read,with great interest,the comprehensive review by Villavicencio Kim J and Wu GY that systematically addressed the issue of liver enzyme elevation in celiac disease(CD)patients.1 The Authors reviewed,in detail,the most relevant studies reporting the frequency of liver enzyme elevation in CD patients and the possible causes,discussing the hypothesis that this elevation may be a clue to associated liver disease or an epiphenomenon,possibly secondary to the increased intestinal permeability that is known to characterize CD patients,especially at diagnosis,before starting a gluten-free diet.

关键词： diagnosis patients liver

Engagement of sialylated glycans with Siglec receptors on suppressive myeloid cells inhibits anticancer immunity via CCL2

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Cellular & Molecular Immunology 2024年第5期21卷 495-509页

作者： Ronja Wieboldt Michael Sandholzer Emanuele Carlini Chia-wei Lin Anastasiya Börsch Andreas Zingg Didier Lardinois Petra Herzig Leyla Don Alfred Zippelius Heinz Läubli Natalia Rodrigues Mantuano laboratory for Cancer Immunotherapy Department of BiomedicineUniversity Hospital and University of BaselBaselSwitzerland. Functional genomics Center Zurich ETH ZurichZurichSwitzerland. bioinformatics Core Facility Department of BiomedicineUniversity of Basel and Swiss Institute of BioinformaticsBaselSwitzerland. Department of Thoracic Surgery University Hospital BaselBaselSwitzerland. laboratory of Cancer Immunology Department of BiomedicineUniversity Hospital and University of BaselBaselSwitzerland. Division of Oncology University Hospital BaselBaselSwitzerland.

The overexpression of sialic acids on glycans,called hypersialylation,is a common alteration found in cancer *** glycans can enhance immune evasion by interacting with sialic acid-binding immunoglobulin-like lectin(Siglec)receptors on tumorinfiltrating immune ***,we investigated the effect of sialylated glycans and their interaction with Siglec receptors on myeloid-derived suppressor cells(MDSCs).We found that MDSCs derived from the blood of lung cancer patients and tumor-bearing mice strongly express inhibitory Siglec receptors and are highly *** murine cancer models of emergency myelopoiesis,Siglec-E knockout in myeloid cells resulted in prolonged survival and increased tumor infiltration of activated T *** suppressive myeloid cells by blocking Siglec receptors or desialylation strongly reduced their suppressive *** further identified CCL2 as a mediator involved in T-cell suppression upon interaction between sialoglycans and Siglec receptors on *** results demonstrated that sialylated glycans inhibit anticancer immunity by modulating CCL2 expression.

关键词： sialoglycans Sialic acid-binding immunoglobulin-like lectin tumor microenvironment myeloid derived suppressor cells

The Genome Sequence Archive Family: Toward Explosive Data Growth and Diverse Data Types

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genomics, Proteomics & bioinformatics 2021年第4期19卷 578-583页

作者： Tingting Chen Xu Chen Sisi Zhang Junwei Zhu Bixia Tang Anke Wang Lili Dong Zhewen Zhang Caixia Yu Yanling Sun Lianjiang Chi Huanxin Chen Shuang Zhai Yubin Sun Li Lan Xin Zhang Jingfa Xiao Yiming Bao Yanqing Wang Zhang Zhang Wenming Zhao China National Center for Bioinformation Beijing 100101China National genomics Data Center Beijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China CAS Key laboratory of Genome Sciences and Information Beijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China CAS Key laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China

The Genome Sequence Archive(GSA)is a data repository for archiving raw sequence data,which provides data storage and sharing services for worldwide scientific *** explosive data growth with diverse data types,here we present the GSA family by expanding into a set of resources for raw data archive with different purposes,namely,GSA(https://***/gsa/),GSA for Human(GSA-Human,https://***/gsa-human/),and Open Archive for Miscellaneous Data(OMIX,https://***/omix/).Compared with the 2017 version,GSA has been significantly updated in data model,online functionalities,and web ***-Human,as a new partner of GSA,is a data repository specialized in human genetics-related data with controlled access and ***,as a critical complement to the two resources mentioned above,is an open archive for miscellaneous ***,all these resources form a family of resources dedicated to archiving explosive data with diverse types,accepting data submissions from all over the world,and providing free open access to all publicly available data in support of worldwide research activities.

关键词： Genome Sequence Archive GSA GSA-Human OMIX

Fine mapping of the awn gene on chromosome 4 in rice by association and linkage analyses

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Chinese Science Bulletin 2011年第9期56卷 835-839页

作者： HU GuangLong ZHANG DongLing PAN HuiQiao LI Ben WU JianTao ZHOU XueYa ZHANG QunYuan ZHOU Lei YAO GuoXin LI JunZhou LI JinJie ZHANG HongLiang LI ZiChao Key laboratory of Crop genomics and Genetic Improvement of Ministry ofAgriculture Beijing Key Laboratory of Crop Genetic Improvement College of Agronomy and Biotechnology China Agricultural University Beijing 100193 China Key laboratory of Btomformattcs and bioinformatics Division of Ministry of Education Tsinghua National Laboratory for Information Sciences and Technology Department of Automation Tsinghua University Beijing 100084 China Division of Statistical genomics Washington University School of Medicine St Louis MO USA

Awnness is a key trait in rice domestication, yet no studies have been conducted on fine mapping or association mapping of the rice awn gene. In this study, we investigated the awnness and genotype of a core collection of 303 cultivated rice varieties and a BC5F2 segregating population of 200 individuals. Combining association and linkage analyses, we mapped the awnness related genes to chromosome 4. Primary association analysis using 24 SSR markers revealed five loci significantly associated with awnness on chromosome 4. The associated markers cover previously identified regions. Fine association mapping was conducted using another 29 markers within a 4-Mb region, covering the associated marker in34, which is close to the awn gene Awn4.1. Seven associated markers were revealed, distributed over an 870-kb region. Combining the fine association mapping and linkage analysis of awnness in the 200 BC5F2 segregating population, we finally identified a 330-kb region as the candidate region for Awn4.1. The results indicate that combining association mapping and linkage mapping provides an efficient and precise approach to both genome-wide mapping and fine mapping of rice genes.

关键词： 4号染色体水稻品种连锁分析精细定位基因图谱协会 SSR标记分离群体

Whole Genome Analyses of Chinese Population and De Novo Assembly of A Northern Han Genome

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genomics, Proteomics & bioinformatics 2019年第3期17卷 229-247页

作者： Zhenglin Du Liang Ma Hongzhu Qu Wei Chen Bing Zhang Xi Lu Weibo Zhai Xin Sheng Yongqiao Sun Wenjie Li Meng Lei Qiuhui Qi Na Yuan Shuo Shi Jingyao Zeng Jinyue Wang Yadong Yang Qi Liu Yaqiang Hong Lili Dong Zhewen Zhang Dong Zou Yanqing Wang Shuhui Song Fan Liu Xiangdong Fang Hua Chen Xin Liu Jingfa Xiao Changqing Zeng Beijing Institute of genomics Chinese Academy of SciencesBeijing 100101China BIG Data Center Beijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China CAS Key laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China CAS Key laboratory of Genome Sciences and Information Beijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China

To unravel the genetic mechanisms of disease and physiological traits,it requires comprehensive sequencing analysis of large sample size in Chinese ***,we report the primary results of the Chinese Academy of Sciences Precision Medicine Initiative(CASPMI)project launched by the Chinese Academy of Sciences,including the de novo assembly of a northern Han reference genome(NH1.0)and whole genome analyses of 597 healthy people coming from most areas in *** the two existing reference genomes for Han Chinese(YH and HX1)were both from the south,we constructed NH1.0,a new reference genome from a northern individual,by combining the sequencing strategies of PacBio,10×genomics,and Bionano *** this integrated approach,we obtained an N50 scaffold size of 46.63 Mb for the NH1.0 genome and performed a comparative genome analysis of NH1.0 with YH and *** order to generate a genomic variation map of Chinese populations,we performed the whole-genome sequencing of 597 participants and identified 24.85 million(M)single nucleotide variants(SNVs),3.85 M small indels,and 106,382 structural *** the association analysis with collected phenotypes,we found that the T allele of rs1549293 in KAT8 significantly correlated with the waist circumference in northern Han ***,significant genetic diversity in MTHFR,TCN2,FADS1,and FADS2,which associate with circulating folate,vitamin B12,or lipid metabolism,was observed between northerners and ***,for the homocysteine-increasing allele of rs1801133(MTHFR 677T),we hypothesize that there exists a “comfort”zone for a high frequency of 677T between latitudes of 35–45 degree *** together,our results provide a high-quality northern Han reference genome and novel population-specific data sets of genetic variants for use in the personalized and precision medicine.

关键词： De novo assembly Reference genome Variation map Phenotype association Large population

A sensitive one-pot ROA assay for rapid miRNA detection

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aBIOTECH 2024年第3期5卷 298-308页

作者： Zhihao Hou Wenpeng Deng Alun Li Ya Zhang Jianye Chang Xinyue Guan Yuxiao Chang Kaile Wang Xinjie Wang Jue Ruan Shenzhen Branch Guangdong Laboratory of Lingnan Modern AgricultureGenome Analysis Laboratory of the Ministry of Agriculture and Rural AffairsAgricultural Genomics Institute at ShenzhenChinese Academy of Agricultural SciencesShenzhen 518120China Hubei Key laboratory of Agricultural bioinformatics College of InformaticsHuazhong Agricultural UniversityWuhan 430070China Department of Systems Biology UT MD Anderson Cancer CenterHoustonTX 77030USA

MicroRNAs(miRNAs)and short RNA fragments(18–25 nt)are crucial biomarkers in biological research and disease ***,their accurate and rapid detection remains a challenge,largely due to their low abundance,short length,and sequence *** this study,we report on a highly sensitive,one-step RNA O-circle amplification(ROA)assay for rapid and accurate miRNA *** ROA assay commences with the hybridization of a circular probe with the test RNA,followed by a linear rolling circle amplification(RCA)using *** amplification process is facilitated by U-nick reactions,which lead to an exponential amplification for *** optimized conditions,assays can be completed within an hour,producing an amplification yield up to the microgram level,with a detection limit as low as 0.15 fmol(6 pM).Notably,the ROA assay requires only one step,and the results can be easily read visually,making it *** ROA assay has proven effective in detecting various miRNAs and phage ***,the ROA assay offers a user-friendly,rapid,and accurate solution for miRNA detection.

关键词： miRNA Rolling circle amplification(RCA) Sensitive detection Fluorescence detection