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      Cancer LncRNA Census 2 (CLC2): an enhanced resource reveals clinical features of cancer lncRNAs

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          Abstract

          Long non-coding RNAs (lncRNAs) play key roles in cancer and are at the vanguard of precision therapeutic development. These efforts depend on large and high-confidence collections of cancer lncRNAs. Here, we present the Cancer LncRNA Census 2 (CLC2). With 492 cancer lncRNAs, CLC2 is 4-fold greater in size than its predecessor, without compromising on strict criteria of confident functional/genetic roles and inclusion in the GENCODE annotation scheme. This increase was enabled by leveraging high-throughput transposon insertional mutagenesis screening data, yielding 92 novel cancer lncRNAs. CLC2 makes a valuable addition to existing collections: it is amongst the largest, contains numerous unique genes (not found in other databases) and carries functional labels (oncogene/tumour suppressor). Analysis of this dataset reveals that cancer lncRNAs are impacted by germline variants, somatic mutations and changes in expression consistent with inferred disease functions. Furthermore, we show how clinical/genomic features can be used to vet prospective gene sets from high-throughput sources. The combination of size and quality makes CLC2 a foundation for precision medicine, demonstrating cancer lncRNAs’ evolutionary and clinical significance.

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          Graphical Abstract

          Cancer LncRNA Census 3 integrates manual and automated curation to identify high confidence functional cancer lncRNAs, whose disease roles are supported by a range of clinical features.

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          Most cited references70

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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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            Analyzing real-time PCR data by the comparative CT method

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              The NHGRI-EBI GWAS Catalog of published genome-wide association studies, targeted arrays and summary statistics 2019

              Abstract The GWAS Catalog delivers a high-quality curated collection of all published genome-wide association studies enabling investigations to identify causal variants, understand disease mechanisms, and establish targets for novel therapies. The scope of the Catalog has also expanded to targeted and exome arrays with 1000 new associations added for these technologies. As of September 2018, the Catalog contains 5687 GWAS comprising 71673 variant-trait associations from 3567 publications. New content includes 284 full P-value summary statistics datasets for genome-wide and new targeted array studies, representing 6 × 109 individual variant-trait statistics. In the last 12 months, the Catalog's user interface was accessed by ∼90000 unique users who viewed >1 million pages. We have improved data access with the release of a new RESTful API to support high-throughput programmatic access, an improved web interface and a new summary statistics database. Summary statistics provision is supported by a new format proposed as a community standard for summary statistics data representation. This format was derived from our experience in standardizing heterogeneous submissions, mapping formats and in harmonizing content. Availability: https://www.ebi.ac.uk/gwas/.
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                Author and article information

                Contributors
                Journal
                NAR Cancer
                NAR Cancer
                narcancer
                NAR Cancer
                Oxford University Press
                2632-8674
                June 2021
                14 April 2021
                14 April 2021
                : 3
                : 2
                : zcab013
                Affiliations
                Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern , Bern 3010, Switzerland
                Graduate School of Cellular and Biomedical Sciences, University of Bern , Bern 3012, Switzerland
                Department for BioMedical Research, University of Bern , Bern 3008, Switzerland
                Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern , Bern 3010, Switzerland
                Graduate School of Cellular and Biomedical Sciences, University of Bern , Bern 3012, Switzerland
                Department for BioMedical Research, University of Bern , Bern 3008, Switzerland
                Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern , Bern 3010, Switzerland
                Graduate School of Cellular and Biomedical Sciences, University of Bern , Bern 3012, Switzerland
                Department for BioMedical Research, University of Bern , Bern 3008, Switzerland
                Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern , Bern 3010, Switzerland
                Department for BioMedical Research, University of Bern , Bern 3008, Switzerland
                Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern , Bern 3010, Switzerland
                Department for BioMedical Research, University of Bern , Bern 3008, Switzerland
                Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern , Bern 3010, Switzerland
                Department for BioMedical Research, University of Bern , Bern 3008, Switzerland
                Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern , Bern 3010, Switzerland
                Department for BioMedical Research, University of Bern , Bern 3008, Switzerland
                School of Biology and Environmental Science, University College Dublin , Dublin D04 V1W8, Ireland
                Conway Institute of Biomedical and Biomolecular Research, University College Dublin , Dublin D04 V1W8, Ireland
                Author notes
                To whom correspondence should be addressed. Tel: +353 1 716 7777; Email: rory.johnson@ 123456ucd.ie
                Author information
                https://orcid.org/0000-0002-7990-0559
                https://orcid.org/0000-0002-5844-2974
                https://orcid.org/0000-0003-4607-2782
                Article
                zcab013
                10.1093/narcan/zcab013
                8210278
                34316704
                044bf017-9883-4008-9a32-f07cae8a7124
                © The Author(s) 2021. Published by Oxford University Press on behalf of NAR Cancer.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 17 March 2021
                : 12 March 2021
                : 15 October 2020
                Page count
                Pages: 15
                Funding
                Funded by: Swiss National Science Foundation, DOI 10.13039/501100001711;
                Funded by: Medical Faculty of the University of Bern;
                Funded by: University Hospital of Bern;
                Funded by: Helmut Horten Stiftung, DOI 10.13039/501100013850;
                Funded by: Krebsliga Schweiz, DOI 10.13039/501100004361;
                Award ID: 4534–08-2018
                Funded by: Science Foundation Ireland, DOI 10.13039/501100001602;
                Award ID: 18/FRL/6194
                Categories
                AcademicSubjects/SCI00030
                AcademicSubjects/SCI00980
                AcademicSubjects/SCI01060
                AcademicSubjects/SCI01140
                AcademicSubjects/SCI01180
                Cancer Data Resource

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