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      TISMO: syngeneic mouse tumor database to model tumor immunity and immunotherapy response

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          Abstract

          Syngeneic mouse models are tumors derived from murine cancer cells engrafted on genetically identical mouse strains. They are widely used tools for studying tumor immunity and immunotherapy response in the context of a fully functional murine immune system. Large volumes of syngeneic mouse tumor expression profiles under different immunotherapy treatments have been generated, although a lack of systematic collection and analysis makes data reuse challenging. We present Tumor Immune Syngeneic MOuse (TISMO), a database with an extensive collection of syngeneic mouse model profiles with interactive visualization features. TISMO contains 605 in vitro RNA-seq samples from 49 syngeneic cancer cell lines across 23 cancer types, of which 195 underwent cytokine treatment. TISMO also includes 1518 in vivo RNA-seq samples from 68 syngeneic mouse tumor models across 19 cancer types, of which 832 were from immune checkpoint blockade (ICB) studies. We manually annotated the sample metadata, such as cell line, mouse strain, transplantation site, treatment, and response status, and uniformly processed and quality-controlled the RNA-seq data. Besides data download, TISMO provides interactive web interfaces to investigate whether specific gene expression, pathway enrichment, or immune infiltration level is associated with differential immunotherapy response. TISMO is available at http://tismo.cistrome.org.

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          Most cited references37

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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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            STAR: ultrafast universal RNA-seq aligner.

            Accurate alignment of high-throughput RNA-seq data is a challenging and yet unsolved problem because of the non-contiguous transcript structure, relatively short read lengths and constantly increasing throughput of the sequencing technologies. Currently available RNA-seq aligners suffer from high mapping error rates, low mapping speed, read length limitation and mapping biases. To align our large (>80 billon reads) ENCODE Transcriptome RNA-seq dataset, we developed the Spliced Transcripts Alignment to a Reference (STAR) software based on a previously undescribed RNA-seq alignment algorithm that uses sequential maximum mappable seed search in uncompressed suffix arrays followed by seed clustering and stitching procedure. STAR outperforms other aligners by a factor of >50 in mapping speed, aligning to the human genome 550 million 2 × 76 bp paired-end reads per hour on a modest 12-core server, while at the same time improving alignment sensitivity and precision. In addition to unbiased de novo detection of canonical junctions, STAR can discover non-canonical splices and chimeric (fusion) transcripts, and is also capable of mapping full-length RNA sequences. Using Roche 454 sequencing of reverse transcription polymerase chain reaction amplicons, we experimentally validated 1960 novel intergenic splice junctions with an 80-90% success rate, corroborating the high precision of the STAR mapping strategy. STAR is implemented as a standalone C++ code. STAR is free open source software distributed under GPLv3 license and can be downloaded from http://code.google.com/p/rna-star/.
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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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                Author and article information

                Contributors
                Journal
                Nucleic Acids Res
                Nucleic Acids Res
                nar
                Nucleic Acids Research
                Oxford University Press
                0305-1048
                1362-4962
                07 January 2022
                17 September 2021
                17 September 2021
                : 50
                : D1
                : D1391-D1397
                Affiliations
                Department of Data Science, Dana Farber Cancer Institute , Boston, MA 02215, USA
                Department of Biostatistics, Harvard T.H. Chan School of Public Health , Boston, MA 02215, USA
                Department of Data Science, Dana Farber Cancer Institute , Boston, MA 02215, USA
                Department of Biomedical Informatics, Harvard Medical School , Boston, MA 02115 USA
                Department of Data Science, Dana Farber Cancer Institute , Boston, MA 02215, USA
                Department of Data Science, Dana Farber Cancer Institute , Boston, MA 02215, USA
                Department of Data Science, Dana Farber Cancer Institute , Boston, MA 02215, USA
                Department of Data Science, Dana Farber Cancer Institute , Boston, MA 02215, USA
                School of Life Science and Technology, Tongji University , Shanghai, 200060, China
                Department of Medical Oncology, Dana-Farber Cancer Institute , Boston, MA 02215, USA
                Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute , Boston, MA 02215, USA
                Department of Data Science, Dana Farber Cancer Institute , Boston, MA 02215, USA
                Department of Biostatistics, Harvard T.H. Chan School of Public Health , Boston, MA 02215, USA
                Department of Data Science, Dana Farber Cancer Institute , Boston, MA 02215, USA
                Department of Biostatistics, Harvard T.H. Chan School of Public Health , Boston, MA 02215, USA
                Department of Data Science, Dana Farber Cancer Institute , Boston, MA 02215, USA
                Department of Medical Oncology, Dana-Farber Cancer Institute , Boston, MA 02215, USA
                Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute , Boston, MA 02215, USA
                Department of Data Science, Dana Farber Cancer Institute , Boston, MA 02215, USA
                Department of Biostatistics, Harvard T.H. Chan School of Public Health , Boston, MA 02215, USA
                Department of Medical Oncology, Dana-Farber Cancer Institute , Boston, MA 02215, USA
                Broad Institute of Harvard and Massachusetts Institute of Technology , Cambridge, MA 02129, USA
                Department of Medical Oncology, Dana-Farber Cancer Institute , Boston, MA 02215, USA
                Department of Medical Oncology, Dana-Farber Cancer Institute , Boston, MA 02215, USA
                Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute , Boston, MA 02215, USA
                Department of Data Science, Dana Farber Cancer Institute , Boston, MA 02215, USA
                Department of Biostatistics, Harvard T.H. Chan School of Public Health , Boston, MA 02215, USA
                Broad Institute of Harvard and Massachusetts Institute of Technology , Cambridge, MA 02129, USA
                Broad Institute of Harvard and Massachusetts Institute of Technology , Cambridge, MA 02129, USA
                Center for Cancer Research, Massachusetts General Hospital, Harvard Medical School , Charlestown, MA 02114, USA
                Department of Medical Oncology, Dana-Farber Cancer Institute , Boston, MA 02215, USA
                Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute , Boston, MA 02215, USA
                Department of Medical Oncology, Dana-Farber Cancer Institute , Boston, MA 02215, USA
                Department of Medical Oncology, Dana-Farber Cancer Institute , Boston, MA 02215, USA
                Department of Surgery, Brigham and Women's Hospital , Boston, MA 02215, USA
                Broad Institute of Harvard and Massachusetts Institute of Technology , Cambridge, MA 02129, USA
                Center for Cancer Research, Massachusetts General Hospital, Harvard Medical School , Charlestown, MA 02114, USA
                Department of Data Science, Dana Farber Cancer Institute , Boston, MA 02215, USA
                Department of Biostatistics, Harvard T.H. Chan School of Public Health , Boston, MA 02215, USA
                Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute , Boston, MA 02215, USA
                Author notes
                To whom correspondence should be addressed. Tel: +1 617 632 2472; Fax: +1 617 632 2444; Email: xsliu@ 123456ds.dfci.harvard.edu
                Correspondence may also be addressed to Zexian Zeng. Tel: +1 617 632 6052; Fax: +1 617 632 6062; Email: zzeng@ 123456ds.dfci.harvard.edu

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

                Author information
                https://orcid.org/0000-0002-3905-3244
                https://orcid.org/0000-0002-5374-7314
                https://orcid.org/0000-0002-8213-1658
                https://orcid.org/0000-0003-4736-7339
                Article
                gkab804
                10.1093/nar/gkab804
                8728303
                34534350
                78741be7-8d10-46aa-8a4d-cc166f6949f6
                © 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 License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 16 September 2021
                : 28 August 2021
                : 28 July 2021
                Page count
                Pages: 7
                Funding
                Funded by: Breast Cancer Research Foundation, DOI 10.13039/100001006;
                Award ID: BCRF-20-100
                Funded by: National Institutes of Health, DOI 10.13039/100000002;
                Award ID: R01CA234018
                Award ID: U24CA224316
                Award ID: T15LM007092
                Funded by: Sara Elizabeth O’Brien Trust, DOI 10.13039/100003212;
                Funded by: Dana-Farber Cancer Institute, DOI 10.13039/100007886;
                Categories
                AcademicSubjects/SCI00010
                Database Issue

                Genetics
                Genetics

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