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Results GREEKC



The Knowledge Commons

The analysis of gene regulation by transcription factor-mediated mechanisms is key to understanding how genomic information determines cellular differentiation and function. This regulation involves a coordinated interaction between various types of transcription factors, the DNA regions where they engage in gene-specific transcription regulation and the specific epigenetic context that defines the accessibility and proximity to their target genes. Systems approaches to study this require ample access to all knowledge that has been obtained and such knowledge should be available from public databases: The Knowledge Commons.


The COST Action Gene Regulation Ensemble Effort for the Knowledge Commons was proposed by the Gene Regulation Consortium (GRECO) and designed to improve the development of the Gene Regulation Knowledge Commons (GRKC): ‘The collection of freely accessible information resources, with data well annotated with unambiguous descriptors according to quality criteria and standards that allow seamless integration and interoperability as well as automated computational access with third-party software. GREEKC has worked toward improving the resources contributing to the GRKC by coordinating efforts in building and making available high-quality, curated databases, following a responsible research and innovation (RRI) approach. This RRI approach proved to be an extremely good fit with the main use of COST Actions: bringing together people in one room who would not normally discuss or consult each other.



Through the organization of nine Workshops, the GREEKC COST Action discussed improvements of the Sequence Ontology and the Gene Ontology, and the testing and use of curation tools including Noctua (which allows Gene Ontology-Causal Activity Modeling GO-CAM)) and Visual Syntax Markup (which aids a curator in the construction of annotations in a readable sentence format). Discussions stimulated the development of new curation guidelines, workflows, and data standards for the annotation of gene regulators at levels of proteins, ncRNA, gene, nucleotide sequence and interactions, regulatory complexes, and network information flow. A critical assessment was done to define what constitutes a DNA binding Transcription Factor, resulting in the GREEKC dbTF list. Given the importance of computationally generated knowledge, the crucial role of the Positional Weight Matrix (PWM) for predicting TF-TG interactions was the inspiration for a comprehensive benchmarking of public PWM models against large experimental reference sets, resulting in benchmarking protocols for future use.

GREEKC also coordinated the new annotation standard ‘Minimum Information about a Molecular Interaction Causal Statement’ (MI2CAST) and the data exchange language CausalTAB (the MITAB 2.8 format), for producing and sharing causal (regulatory) molecular interaction data. The use of text mining was discussed as a way to extract knowledge about regulatory interactions of transcription factors with target genes automatically from MedLine abstracts (, and the results (a large corpus of TF-TG sentences) was made available through the PSICQUIC web service and through the Cytoscape App BioGateway, allowing a network builder to validate the quality of the text mining result by linking out to the ExTRI sentence in the abstract.


GREEKC Training Schools results


Summary of results document

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Summary of results document

To appear in Biochimica et Biophysica Acta as Gene Ontology representation for transcription factor functions.


  • Mulero-Hernández J, Fernández-Breis, JT. Analysis of the landscape of human enhancer sequences in biological databases. CSBJ 2022, DOI: 10.1016/j.csbj.2022.05.045.

    Ershova AS, Eliseeva IA, Nikonov OS, Fedorova AD, Vorontsov IE, Papatsenko D, Kulakovskiy IV. Enhanced C/EBP binding to G· T mismatches facilitates fixation of CpG mutations in cancer and adult stem cells. Cell Reports. 2021 Jun 8;35(10):109221. DOI: 10.1016/j.celrep.2021.109221

    Abramov S, Boytsov A, Bykova D, Penzar DD, Yevshin I, Kolmykov SK, Fridman MV, Favorov AV, Vorontsov IE, Baulin E, Kolpakov F. Landscape of allele-specific transcription factor binding in the human genome. Nature Communications. 2021 May 12;12(1):1-5. DOI: 10.1038/s41467-021-23007-0

    Carbon S, Douglass E, Good BM, Unni DR, Harris NL, Mungall CJ, Basu S, Chisholm RL, Dodson RJ, Hartline E, Fey P. The Gene Ontology resource: enriching a GOld mine. Nucleic Acids Research. 2021 Jan 8;49(D1):D325-34. DOI: 10.1093/nar/gkaa1113

    Gene Ontology Consortium. The gene ontology resource: 20 years and still GOing strong. Nucleic acids research. 2019 Jan 8;47(D1):D330-8. DOI: 10.1093/nar/gky1055

    Vera-Ramos JA, Juanes-Cortés B, Fernández-Breis JT, Gaudet P, Kuiper M, Lægreid A, Logie C, García MD, Schulz S. An Example of Multimodal Biological Knowledge Representation. InJOWO 2019. //

    Ambrosini G, Vorontsov I, Penzar D, Groux R, Fornes O, Nikolaeva DD, Ballester B, Grau J, Grosse I, Makeev V, Kulakovskiy I. Insights gained from a comprehensive all-against-all transcription factor binding motif benchmarking study. Genome biology. 2020 Dec;21:1-8. DOI: 10.1186/s13059-020-01996-3

    Perfetto L, Acencio ML, Bradley G, Cesareni G, Del Toro N, Fazekas D, Hermjakob H, Korcsmaros T, Kuiper M, Lægreid A, Lo Surdo P. CausalTAB: the PSI-MITAB 2.8 updated format for signalling data representation and dissemination. Bioinformatics. 2019 Oct 1;35(19):3779-85. DOI: 10.1093/bioinformatics/btz132

    Touré V, Vercruysse S, Acencio ML, Lovering RC, Orchard S, Bradley G, Casals-Casas C, Chaouiya C, Del-Toro N, Flobak Å, Gaudet P. The minimum information about a molecular interaction causal statement (MI2CAST). Bioinformatics. 2020 Apr 27. DOI: 10.1093/bioinformatics/btaa622

    Panni S, Lovering RC, Porras P, Orchard S. Non-coding RNA regulatory networks. Biochimica et Biophysica Acta (BBA)-Gene Regulatory Mechanisms. 2020 Jun 1;1863(6):194417. DOI: 10.1016/j.bbagrm.2019.194417

    Chatterjee A. Pure for me or impure for us: Pollution in the Gene Regulation Knowledge Commons. //

    Gabrielsen AM. Openness and trust in data-intensive science: the case of biocuration. Medicine, Health Care and Philosophy. 2020 Sep;23(3):497-504. DOI: 10.1007/s11019-020-09960-5

    Nydal R, Bennett G, Kuiper M, Lægreid A. Silencing trust: confidence and familiarity in re-engineering knowledge infrastructures. Medicine, Health Care and Philosophy. 2020 Sep;23:471-84. DOI: 10.1007/s11019-020-09957-0

    Shelley-Egan C, Gjefsen MD, Nydal R. Consolidating RRI and Open Science: understanding the potential for transformative change. Life Sciences, Society and Policy. 2020 Dec;16(1):1-4. DOI: 10.1186/s40504-020-00103-5

  • Sant DW, Sinclair M, Mungall CJ, Schulz S, Zerbino D, Lovering RC, Logie C, Eilbeck K. Sequence Ontology terminology for gene regulation. Biochimica et Biophysica Acta (BBA)-Gene Regulatory Mechanisms. 2021 Oct 1;1864(10):194745. DOI: 10.1016/j.bbagrm.2021.194745

    Velthuijs N, Meldal B, Geessinck Q, Porras P, Medvedeva Y, Zubritskiy A, Orchard S, Logie C. Integration of transcription coregulator complexes with sequence-specific DNA-binding factor interactomes. Biochimica et Biophysica Acta (BBA)-Gene Regulatory Mechanisms. 2021 Oct 1;1864(10):194749. DOI: 10.1016/j.bbagrm.2021.194749

    Gaudet P, Logie C, Lovering RC, Kuiper M, Lægreid A, Thomas PD. Gene Ontology representation for transcription factor functions. Biochimica et Biophysica Acta (BBA)-Gene Regulatory Mechanisms. 2021 Nov 1;1864(11-12):194752. DOI: 10.1016/j.bbagrm.2021.194752

    Díaz-Rodríguez, M., Lithgow-Serrano, O., Guadarrama-García, F., Tierrafría, V.H., Gama-Castro, S., Solano-Lira, H., Salgado, H., Rinaldi, F., Méndez-Cruz, C.F. and Collado-Vides, J., 2021. Lisen&Curate: A platform to facilitate gathering textual evidence for curation of regulation of transcription initiation in bacteria. Biochimica et Biophysica Acta (BBA)-Gene Regulatory Mechanisms1864(11-12), p.194753. DOI: 10.1016/j.bbagrm.2021.194753

    Lovering RC, Gaudet P, Acencio ML, Ignatchenko A, Jolma A, Fornes O, Kuiper M, Kulakovskiy IV, Lægreid A, Martin MJ, Logie C. A GO catalogue of human DNA-binding transcription factors. Biochimica et Biophysica Acta (BBA)-Gene Regulatory Mechanisms. 2021 Nov 1;1864(11-12):194765. DOI: 10.1016/j.bbagrm.2021.194765

    Cortés BJ, Vera-Ramos JA, Lovering RC, Gaudet P, Laegreid A, Logie C, Schulz S, del Mar Roldán-García M, Kuiper M, Fernández-Breis JT. Formalization of gene regulation knowledge using ontologies and gene ontology causal activity models. Biochimica et Biophysica Acta (BBA)-Gene Regulatory Mechanisms. 2021 Nov 1;1864(11-12):194766. DOI: 10.1016/j.bbagrm.2021.194766

    Bonello J, Cachia E, Alfino N. AutoFAIR-A portal for automating FAIR assessments for bioinformatics resources. Biochimica et Biophysica Acta (BBA)-Gene Regulatory Mechanisms. 2022 Jan 1;1865(1):194767. DOI: 10.1016/j.bbagrm.2021.194767

    Kuiper M, Bonello J, Fernández-Breis JT, Bucher P, Futschik ME, Gaudet P, Kulakovskiy IV, Licata L, Logie C, Lovering RC, Makeev VJ. The gene regulation knowledge commons: the action area of GREEKC. Biochimica et Biophysica Acta (BBA)-Gene Regulatory Mechanisms. 2022 Jan 1;1865(1):194768. DOI: 10.1016/j.bbagrm.2021.194768

    Vazquez M, Krallinger M, Leitner F, Kuiper M, Valencia A, Laegreid A. ExTRI: Extraction of transcription regulation interactions from literature. Biochimica et Biophysica Acta (BBA)-Gene Regulatory Mechanisms. 2022 Jan 1;1865(1):194778. DOI: 10.1016/j.bbagrm.2021.194778

    Chatterjee A, Kuiper M, Swierstra T. Dealing with different conceptions of pollution in the Gene Regulation Knowledge Commons. Biochimica et Biophysica Acta (BBA)-Gene Regulatory Mechanisms. 2021 Dec 28:194779. DOI: 10.1016/j.bbagrm.2021.194779

    Cokan KB, Hancock JM, Spindelböck W, Režen T, Juvan P, Rozman D. Matching mouse models to specific human liver disease states by comparative functional genomics of mouse and human datasets. Biochimica et Biophysica Acta (BBA)-Gene Regulatory Mechanisms. 2021 Dec 29:194785. DOI: 10.1016/j.bbagrm.2021.194785

    Logie C. From why to how; The gene expression knowledge commons. Biochimica et Biophysica acta. Gene Regulatory Mechanisms. 2021 Dec 16;1865(1):194783-. DOI: 10.1016/j.bbagrm.2021.194783

  • Almagro Hernández G. Modelos de análisis semántico de información y conocimiento genético y genómico para el estudio de enfermedades genéticas y cáncer. Proyecto de investigación:. 2021 Jan 14. //

    Touré V. Improving the FAIRness of causal interactions in systems biology. 2020 //

    Touré V, Zobolas J, Kuiper M, Vercruysse S. CausalBuilder: bringing the MI2CAST causal interaction annotation standard to the curator. Database. 2021 Jan 1;2021. DOI: 10.1093/database/baaa107

    Zobolas J, Touré V, Kuiper M, Vercruysse S. UniBioDicts: unified access to biological dictionaries. Bioinformatics. 2021 Jan 1;37(1):143-4. DOI: 10.1093/bioinformatics/btaa1065

    Porras P, Barrera E, Bridge A, Del-Toro N, Cesareni G, Duesbury M, Hermjakob H, Iannuccelli M, Jurisica I, Kotlyar M, Licata L. Towards a unified open access dataset of molecular interactions. Nature communications. 2020 Dec 1;11(1):1-2. DOI: 10.1038/s41467-020-19942-z

    Vera-Ramos JA, Roldán-García M, Hurtado S, Fernández-Breis JT, Schulz S. Deconstructing and recycling ontologies: A Gene Regulation ontology use case. 2021. Pending submission. 



UCL Institute of Cardiovascular Science Newsletter

March 2020

Editor – Barbara Kramarz

“Shirin was awarded a Short Term Scientific Mission (STSM) grant from the European Cooperation In Science and Technology (COST) organisation, which allowed her to travel to Università della Calabria in southern Italy for a week-long knowledge exchange meeting with Dr Simona Panni. During this time Simona trained Shirin in capturing molecular interactions between microRNAs and their mRNA targets using the IntAct curation tool, whereas Shirin shared with Simona her knowledge about GO annotation of microRNAs, and trained Simona in using the Gene Ontology Annotation (GOA) curation tool.”

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