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      KOBAS-i: intelligent prioritization and exploratory visualization of biological functions for gene enrichment analysis

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          Abstract

          Gene set enrichment (GSE) analysis plays an essential role in extracting biological insight from genome-scale experiments. ORA (overrepresentation analysis), FCS (functional class scoring), and PT (pathway topology) approaches are three generations of GSE methods along the timeline of development. Previous versions of KOBAS provided services based on just the ORA method. Here we presented version 3.0 of KOBAS, which is named KOBAS-i (short for KOBAS intelligent version). It introduced a novel machine learning-based method we published earlier, CGPS, which incorporates seven FCS tools and two PT tools into a single ensemble score and intelligently prioritizes the relevant biological pathways. In addition, KOBAS has expanded the downstream exploratory visualization for selecting and understanding the enriched results. The tool constructs a novel view of cirFunMap, which presents different enriched terms and their correlations in a landscape. Finally, based on the previous version's framework, KOBAS increased the number of supported species from 1327 to 5944. For an easier local run, it also provides a prebuilt Docker image that requires no installation, as a supplementary to the source code version. KOBAS can be freely accessed at http://kobas.cbi.pku.edu.cn, and a mirror site is available at http://bioinfo.org/kobas.

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          Graphical Abstract

          Framework of KOBAS.

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          Most cited references49

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          Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles

          Although genomewide RNA expression analysis has become a routine tool in biomedical research, extracting biological insight from such information remains a major challenge. Here, we describe a powerful analytical method called Gene Set Enrichment Analysis (GSEA) for interpreting gene expression data. The method derives its power by focusing on gene sets, that is, groups of genes that share common biological function, chromosomal location, or regulation. We demonstrate how GSEA yields insights into several cancer-related data sets, including leukemia and lung cancer. Notably, where single-gene analysis finds little similarity between two independent studies of patient survival in lung cancer, GSEA reveals many biological pathways in common. The GSEA method is embodied in a freely available software package, together with an initial database of 1,325 biologically defined gene sets.
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            clusterProfiler: an R package for comparing biological themes among gene clusters.

            Increasing quantitative data generated from transcriptomics and proteomics require integrative strategies for analysis. Here, we present an R package, clusterProfiler that automates the process of biological-term classification and the enrichment analysis of gene clusters. The analysis module and visualization module were combined into a reusable workflow. Currently, clusterProfiler supports three species, including humans, mice, and yeast. Methods provided in this package can be easily extended to other species and ontologies. The clusterProfiler package is released under Artistic-2.0 License within Bioconductor project. The source code and vignette are freely available at http://bioconductor.org/packages/release/bioc/html/clusterProfiler.html.
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              GSVA: gene set variation analysis for microarray and RNA-Seq data

              Background Gene set enrichment (GSE) analysis is a popular framework for condensing information from gene expression profiles into a pathway or signature summary. The strengths of this approach over single gene analysis include noise and dimension reduction, as well as greater biological interpretability. As molecular profiling experiments move beyond simple case-control studies, robust and flexible GSE methodologies are needed that can model pathway activity within highly heterogeneous data sets. Results To address this challenge, we introduce Gene Set Variation Analysis (GSVA), a GSE method that estimates variation of pathway activity over a sample population in an unsupervised manner. We demonstrate the robustness of GSVA in a comparison with current state of the art sample-wise enrichment methods. Further, we provide examples of its utility in differential pathway activity and survival analysis. Lastly, we show how GSVA works analogously with data from both microarray and RNA-seq experiments. Conclusions GSVA provides increased power to detect subtle pathway activity changes over a sample population in comparison to corresponding methods. While GSE methods are generally regarded as end points of a bioinformatic analysis, GSVA constitutes a starting point to build pathway-centric models of biology. Moreover, GSVA contributes to the current need of GSE methods for RNA-seq data. GSVA is an open source software package for R which forms part of the Bioconductor project and can be downloaded at http://www.bioconductor.org.
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                Author and article information

                Contributors
                Journal
                Nucleic Acids Res
                Nucleic Acids Res
                nar
                Nucleic Acids Research
                Oxford University Press
                0305-1048
                1362-4962
                02 July 2021
                04 June 2021
                04 June 2021
                : 49
                : W1
                : W317-W325
                Affiliations
                Pervasive Computing Research Center, Institute of Computing Technology, Chinese Academy of Sciences, Beijing, 100190, China
                Translational Medicine Collaborative Innovation Center, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University , Shenzhen 518020, China
                Chinese Academy of Sciences, LuoYang Branch of Institute of Computing Technology , Luoyang, 471000, China
                Chinese Academy of Sciences, LuoYang Branch of Institute of Computing Technology , Luoyang, 471000, China
                Chinese Academy of Sciences, LuoYang Branch of Institute of Computing Technology , Luoyang, 471000, China
                School of Traditional Chinese Medicine, Beijing University of Chinese Medicine , ChaoYang District, Beijing 100029, China
                Pervasive Computing Research Center, Institute of Computing Technology, Chinese Academy of Sciences, Beijing, 100190, China
                Pervasive Computing Research Center, Institute of Computing Technology, Chinese Academy of Sciences, Beijing, 100190, China
                Cancer Center, Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences , Zhejiang 315000, China
                School of Traditional Chinese Medicine, Beijing University of Chinese Medicine , ChaoYang District, Beijing 100029, China
                School of Traditional Chinese Medicine, Beijing University of Chinese Medicine , ChaoYang District, Beijing 100029, China
                School of Traditional Chinese Medicine, Beijing University of Chinese Medicine , ChaoYang District, Beijing 100029, China
                Pervasive Computing Research Center, Institute of Computing Technology, Chinese Academy of Sciences, Beijing, 100190, China
                Pervasive Computing Research Center, Institute of Computing Technology, Chinese Academy of Sciences, Beijing, 100190, China
                Center for Bioinformatics, State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University , Beijing 100871, China
                Author notes
                To whom correspondence should be addressed. Tel: +86 010 62755206; Email: konglei@ 123456pku.edu.cn
                Correspondence may also be addressed to Yi Zhao. Tel: +86 010 62600822; Email: biozy@ 123456ict.ac.cn

                The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.

                Author information
                https://orcid.org/0000-0002-5616-6910
                Article
                gkab447
                10.1093/nar/gkab447
                8265193
                34086934
                c095b21a-0797-4561-a575-50c43e3dbbe4
                © The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@ 123456oup.com

                History
                : 09 May 2021
                : 24 April 2021
                : 24 March 2021
                Page count
                Pages: 9
                Funding
                Funded by: National Key Research and Development Program of China, DOI 10.13039/501100012166;
                Award ID: 2016YFB0201700
                Funded by: National Natural Science Foundation of Zhejiang Province;
                Award ID: LY20C060001
                Award ID: LY21C060003
                Funded by: National Natural Science Foundation of China, DOI 10.13039/501100001809;
                Award ID: 32070670
                Funded by: National Key Research and Development Program of China, DOI 10.13039/501100012166;
                Award ID: 2017YFC0908404
                Funded by: Zhejiang Provincial Research Center for Cancer Intelligent Diagnosis and Molecular Technology;
                Award ID: JBZX-202003
                Funded by: National Natural Science Foundation for Young Scholars of China;
                Award ID: 31701149
                Award ID: 31701141
                Categories
                AcademicSubjects/SCI00010
                Web Server Issue

                Genetics
                Genetics

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