title: The Implicitome: A Resource for Rationalizing Gene-Disease Associations.
abstract: High-throughput experimental methods such as medical sequencing and genome-wide association studies (GWAS) identify increasingly large numbers of potential relations between genetic variants and diseases. Both biological complexity (millions of potential gene-disease associations) and the accelerating rate of data production necessitate computational approaches to prioritize and rationalize potential gene-disease relations. Here, we use concept profile technology to expose from the biomedical literature both explicitly stated gene-disease relations (the explicitome) and a much larger set of implied gene-disease associations (the implicitome). Implicit relations are largely unknown to, or are even unintended by the original authors, but they vastly extend the reach of existing biomedical knowledge for identification and interpretation of gene-disease associations. The implicitome can be used in conjunction with experimental data resources to rationalize both known and novel associations. We demonstrate the usefulness of the implicitome by rationalizing known and novel gene-disease associations, including those from GWAS. To facilitate the re-use of implicit gene-disease associations, we publish our data in compliance with FAIR Data Publishing recommendations [https://www.force11.org/group/fairgroup] using nanopublications. An online tool (http://knowledge.bio) is available to explore established and potential gene-disease associations in the context of other biomedical relations.
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Kristina M
authors.initials: KM
authors.lastname: Hettne
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Mark
authors.initials: M
authors.lastname: Thompson
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Herman H H B M
authors.initials: HH
authors.lastname: van Haagen
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Eelke
authors.initials: E
authors.lastname: van der Horst
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Rajaram
authors.initials: R
authors.lastname: Kaliyaperumal
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Eleni
authors.initials: E
authors.lastname: Mina
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Zuotian
authors.initials: Z
authors.lastname: Tatum
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Jeroen F J
authors.initials: JF
authors.lastname: Laros
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.|Department of Medical Informatics, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Erik M
authors.initials: EM
authors.lastname: van Mulligen
authors.affiliation: Department of Medical Informatics, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Martijn
authors.initials: M
authors.lastname: Schuemie
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Emmelien
authors.initials: E
authors.lastname: Aten
authors.affiliation: Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA, United States of America.
authors.forename: Tong Shu
authors.initials: TS
authors.lastname: Li
authors.affiliation: STAR Informatics / Delphinai Corporation, Port Moody, BC, Canada.
authors.forename: Richard
authors.initials: R
authors.lastname: Bruskiewich
authors.affiliation: Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA, United States of America.
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Good
authors.affiliation: Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA, United States of America.
authors.forename: Andrew I
authors.initials: AI
authors.lastname: Su
authors.affiliation: Department of Medical Informatics, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Jan A
authors.initials: JA
authors.lastname: Kors
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Johan
authors.initials: J
authors.lastname: den Dunnen
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Gert-Jan B
authors.initials: GJ
authors.lastname: van Ommen
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Marco
authors.initials: M
authors.lastname: Roos
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Peter A C
authors.initials: PA
authors.lastname: 't Hoen
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.|Dutch Techcentre for Life Sciences, Utrecht, The Netherlands.
authors.forename: Barend
authors.initials: B
authors.lastname: Mons
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.|Leiden Institute for Advanced Computer Science, Leiden, The Netherlands.
authors.forename: Erik A
authors.initials: EA
authors.lastname: Schultes
mesh_terms: D019295:Computational Biology / Q000379:methods*; D030541:Databases, Genetic; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans