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      MELODI: Mining Enriched Literature Objects to Derive Intermediates

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          Abstract

          Background

          The scientific literature contains a wealth of information from different fields on potential disease mechanisms. However, identifying and prioritizing mechanisms for further analytical evaluation presents enormous challenges in terms of the quantity and diversity of published research. The application of data mining approaches to the literature offers the potential to identify and prioritize mechanisms for more focused and detailed analysis.

          Methods

          Here we present MELODI, a literature mining platform that can identify mechanistic pathways between any two biomedical concepts.

          Results

          Two case studies demonstrate the potential uses of MELODI and how it can generate hypotheses for further investigation. First, an analysis of ETS-related gene ERG and prostate cancer derives the intermediate transcription factor SP1, recently confirmed to be physically interacting with ERG. Second, examining the relationship between a new potential risk factor for pancreatic cancer identifies possible mechanistic insights which can be studied in vitro.

          Conclusions

          We have demonstrated the possible applications of MELODI, including two case studies. MELODI has been implemented as a Python/Django web application, and is freely available to use at [ www.melodi.biocompute.org.uk].

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          Most cited references15

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          'Mendelian randomization': can genetic epidemiology contribute to understanding environmental determinants of disease?

          Associations between modifiable exposures and disease seen in observational epidemiology are sometimes confounded and thus misleading, despite our best efforts to improve the design and analysis of studies. Mendelian randomization-the random assortment of genes from parents to offspring that occurs during gamete formation and conception-provides one method for assessing the causal nature of some environmental exposures. The association between a disease and a polymorphism that mimics the biological link between a proposed exposure and disease is not generally susceptible to the reverse causation or confounding that may distort interpretations of conventional observational studies. Several examples where the phenotypic effects of polymorphisms are well documented provide encouraging evidence of the explanatory power of Mendelian randomization and are described. The limitations of the approach include confounding by polymorphisms in linkage disequilibrium with the polymorphism under study, that polymorphisms may have several phenotypic effects associated with disease, the lack of suitable polymorphisms for studying modifiable exposures of interest, and canalization-the buffering of the effects of genetic variation during development. Nevertheless, Mendelian randomization provides new opportunities to test causality and demonstrates how investment in the human genome project may contribute to understanding and preventing the adverse effects on human health of modifiable exposures.
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            SemMedDB: a PubMed-scale repository of biomedical semantic predications.

            Effective access to the vast biomedical knowledge present in the scientific literature is challenging. Semantic relations are increasingly used in knowledge management applications supporting biomedical research to help address this challenge. We describe SemMedDB, a repository of semantic predications (subject-predicate-object triples) extracted from the entire set of PubMed citations. We propose the repository as a knowledge resource that can assist in hypothesis generation and literature-based discovery in biomedicine as well as in clinical decision-making support. The SemMedDB repository is available as a MySQL database for non-commercial use at http://skr3.nlm.nih.gov/SemMedDB. An UMLS Metathesaurus license is required. kilicogluh@mail.nih.gov.
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              Data dredging, bias, or confounding.

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                Author and article information

                Journal
                Int J Epidemiol
                Int J Epidemiol
                ije
                International Journal of Epidemiology
                Oxford University Press
                0300-5771
                1464-3685
                April 2018
                12 January 2018
                12 January 2018
                : 47
                : 2
                : 369-379
                Affiliations
                [1 ]MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK
                [2 ]Cancer Epidemiology and Intelligence Division, Cancer Council Victoria, Melbourne, VIC, Australia
                [3 ]Centre for Epidemiology and Biostatistics, University of Melbourne, Melbourne, VIC, Australia
                [4 ]Physical Activity Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia
                Author notes
                Corresponding author. MRC Integrative Epidemiology Unit (IEU), Bristol Medical School: Population Health Science, Oakfield House, Oakfield Grove, University of Bristol, Bristol BS8 2BN, UK. E-mail: ben.elsworth@ 123456bristol.ac.uk
                Article
                dyx251
                10.1093/ije/dyx251
                5913624
                29342271
                fae2f026-6fab-44ea-90ea-333c6ec10b51
                © The Author(s) 2018. Published by Oxford University Press on behalf of the International Epidemiological Association

                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
                : 2 November 2017
                : 3 January 2018
                Categories
                Software Application Profile

                Public health
                data mining,risk factors,publications
                Public health
                data mining, risk factors, publications

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