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      CeTF: an R/Bioconductor package for transcription factor co-expression networks using regulatory impact factors (RIF) and partial correlation and information (PCIT) analysis

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          Abstract

          Background

          Finding meaningful gene-gene interaction and the main Transcription Factors (TFs) in co-expression networks is one of the most important challenges in gene expression data mining.

          Results

          Here, we developed the R package “CeTF” that integrates the Partial Correlation with Information Theory (PCIT) and Regulatory Impact Factors (RIF) algorithms applied to gene expression data from microarray, RNA-seq, or single-cell RNA-seq platforms. This approach allows identifying the transcription factors most likely to regulate a given network in different biological systems — for example, regulation of gene pathways in tumor stromal cells and tumor cells of the same tumor. This pipeline can be easily integrated into the high-throughput analysis. To demonstrate the CeTF package application, we analyzed gastric cancer RNA-seq data obtained from TCGA (The Cancer Genome Atlas) and found the HOXB3 gene as the second most relevant TFs with a high regulatory impact (TFs-HRi) regulating gene pathways in the cell cycle.

          Conclusion

          This preliminary finding shows the potential of CeTF to list master regulators of gene networks. CeTF was designed as a user-friendly tool that provides many highly automated functions without requiring the user to perform many complicated processes. It is available on Bioconductor ( http://bioconductor.org/packages/CeTF) and GitHub ( http://github.com/cbiagii/CeTF).

          Supplementary Information

          The online version contains supplementary material available at (10.1186/s12864-021-07918-2).

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          Most cited references25

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          Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2

          In comparative high-throughput sequencing assays, a fundamental task is the analysis of count data, such as read counts per gene in RNA-seq, for evidence of systematic changes across experimental conditions. Small replicate numbers, discreteness, large dynamic range and the presence of outliers require a suitable statistical approach. We present DESeq2, a method for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates. This enables a more quantitative analysis focused on the strength rather than the mere presence of differential expression. The DESeq2 package is available at http://www.bioconductor.org/packages/release/bioc/html/DESeq2.html. Electronic supplementary material The online version of this article (doi:10.1186/s13059-014-0550-8) contains supplementary material, which is available to authorized users.
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            Hallmarks of Cancer: The Next Generation

            The hallmarks of cancer comprise six biological capabilities acquired during the multistep development of human tumors. The hallmarks constitute an organizing principle for rationalizing the complexities of neoplastic disease. They include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis. Underlying these hallmarks are genome instability, which generates the genetic diversity that expedites their acquisition, and inflammation, which fosters multiple hallmark functions. Conceptual progress in the last decade has added two emerging hallmarks of potential generality to this list-reprogramming of energy metabolism and evading immune destruction. In addition to cancer cells, tumors exhibit another dimension of complexity: they contain a repertoire of recruited, ostensibly normal cells that contribute to the acquisition of hallmark traits by creating the "tumor microenvironment." Recognition of the widespread applicability of these concepts will increasingly affect the development of new means to treat human cancer. Copyright © 2011 Elsevier Inc. All rights reserved.
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              Complex heatmaps reveal patterns and correlations in multidimensional genomic data.

              Parallel heatmaps with carefully designed annotation graphics are powerful for efficient visualization of patterns and relationships among high dimensional genomic data. Here we present the ComplexHeatmap package that provides rich functionalities for customizing heatmaps, arranging multiple parallel heatmaps and including user-defined annotation graphics. We demonstrate the power of ComplexHeatmap to easily reveal patterns and correlations among multiple sources of information with four real-world datasets.
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                Author and article information

                Contributors
                biagi@usp.br
                rnociti@gmail.com
                daniellebrotto@gmail.com
                osvaldobreno99@gmail.com
                patiruy@gmail.com
                joaopaulo.ximenez@me.com
                davidlafigueiredo@gmail.com
                wilsonjr@usp.br
                Journal
                BMC Genomics
                BMC Genomics
                BMC Genomics
                BioMed Central (London )
                1471-2164
                20 August 2021
                20 August 2021
                2021
                : 22
                : 624
                Affiliations
                [1 ]GRID grid.11899.38, ISNI 0000 0004 1937 0722, Department of Genetics at Ribeirão Preto Medical School, , University of São Paulo, ; Ribeirão Preto, Brazil
                [2 ]Center for Cell-Based Therapy (CEPID/FAPESP), National Institute of Science and Technology in Stem Cell and Cell Therapy (INCTC/CNPq), Regional Blood Center of Ribeirão Preto, Ribeirão Preto, Brazil
                [3 ]GRID grid.507702.7, Institute for Cancer Research, , IPEC, ; Guarapuava, Brazil
                [4 ]GRID grid.11899.38, ISNI 0000 0004 1937 0722, Laboratory of Molecular Morphophysiology and Development, Department of Veterinary Medicine, , Faculty of Animal Science and Food Engineering, University of São Paulo, ; Pirassununga, Brazil
                [5 ]Center for Medical Genomics, HCFMRP/USP, Ribeirão Preto, Brazil
                [6 ]GRID grid.412329.f, ISNI 0000 0001 1581 1066, Department of Medicine, , Midwest State University of Paraná-UNICENTRO, ; Guarapuava, Brazil
                [7 ]GRID grid.11899.38, ISNI 0000 0004 1937 0722, Center for Integrative Systems Biology (CISBi) - NAP/USP, , University of São Paulo, ; Ribeirão Preto, Brazil
                Author information
                http://orcid.org/0000-0001-9364-2886
                Article
                7918
                10.1186/s12864-021-07918-2
                8379792
                34416858
                07a86041-8949-4fcb-900b-a13eb973d91d
                © The Author(s) 2021

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 5 January 2021
                : 30 July 2021
                Funding
                Funded by: CAPES
                Award ID: 88882.378695/2019-01
                Funded by: FAPESP
                Award ID: 2013/08135-2
                Funded by: CISBi-NAP/USP
                Award ID: 12.1.25441.01.2
                Categories
                Software
                Custom metadata
                © The Author(s) 2021

                Genetics
                bioinformatics,r package,r,transcript factors,network
                Genetics
                bioinformatics, r package, r, transcript factors, network

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