*2.4.1.2 Database*

*Cheminformatics and Its Applications*

**EU-OPENSCREEN**

innovation [22].

**2.4 The European research infrastructure consortium (ERIC)** 

processes, such as signaling or metabolic pathways.

encourage scientists at the local level to participate.

*2.4.1 The research infrastructure*

*2.4.1.1 Compound collection*

EU-OPENSCREEN [20] is a community-driven, bottom-up initiative in Europe,

EU-OPENSCREEN is one of 55 research infrastructures listed on the current ESFRI (European Strategy Forum on Research Infrastructures) Roadmap [21] as an 'ESFRI Landmark Project', demonstrating the relevance for the European scientific community and the European Research Area (ERA). It is jointly funded by the research ministries of eight countries (the Czech Republic, Denmark, Finland, Germany, Latvia, Norway, Poland, Spain) and the European Commission. Since April 2018, it operates a European, not-for-profit organization ('European Research Infrastructure Consortium'), which is based in Berlin, Germany, and is legally independent from any university or research institute. EU-OPENSCREEN, and the European Research Infrastructures in general, promote open science and open

Many technology platforms at universities and research institutes predominantly work with the colleagues at their hosting institution. Larger European initiatives often engage with scientists from Western European countries, where these initiatives are based. Reaching out to, and encourage the active participation of, scientists from regions, which are often underrepresented in chemical biology and early drug discovery research, requires a different approach. Through its distributed network of partner sites across its member countries, EU-OPENSCREEN aims to have a more balanced engagement of local science communities. In each member country, a local partner establishes and coordinates a national network—e.g. CZ-OPENSCREEN in the Czech Republic, PL-OPENSCREEN in Poland, NOR-OPENSCREEN in Norway, Drug Discovery and Chemical Biology Consortium (DDCB) in Finland, ChemBioNet in Germany—to raise awareness about the initiative and to efficiently

The EU-OPENSCREEN infrastructure provides open-access to compound libraries, assay development and screening facilities, and medicinal chemistry and informatics platforms. It provides training and serves as a platform for industry

The EU-OPENSCREEN compound collection is a diversity library, which has been designed in a collaborative effort of several partner sites. The library is jointly used by affiliated EU-OPENSCREEN partner sites for primary screening against biological targets solicited from external researchers who developed the appropriate assays. During the design of the library, 100,000 commercially available

which brings together 21 partner sites, i.e. technology platforms and research groups at various universities and research institutions, to form an open-access research infrastructure for chemical biology and early drug discovery. Instead of building an ivory tower, the aim of EU-OPENSCREEN is to establish and operate an infrastructure that facilitates and encourages the engagement with the broader scientific community. In the framework of EU-OPENSCREEN, the partner sites and external researchers collaboratively develop novel tool compounds (or chemical 'probes') that allow researchers to interrogate and study fundamental cellular

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engagement.

In many cases, primary screening data—even from publicly funded programs are not openly accessible by the scientific community. While private organizations, contract research organizations (CROs) and many public-private partnerships do not reveal data on a routine basis, EU-OPENSCREEN is committed to maximizing the re-use and impact of generated bioactivity data for the benefit of the wider scientific community. Therefore, EU-OPENSCREEN's ECBD adheres to the FAIR principles [23] and is closely linked to the ChEMBL [24] database, which will raise the discoverability and re-use of EU-OPENSCREEN's data. Via ECBD and ChEMBL, database users will be drawn from across the global biological and chemical science communities, both from academia and industry. Together with other European life sciences-research infrastructures, EU-OPENSCREEN partners also contribute towards the optimization of technological implementation, integration and interoperability of data and tools within the European Open Science Cloud (EOSC) and participate in the Horizon 2020-funded 'EOSC-Life' project (www.eosc-life.eu/). Another initiative, to which the EU-OPENSCREEN partner

Fraunhofer IME actively contributes, is the Innovative Medicines Initiative (IMI) funded 'FAIRplus' project (https://fairplus-project.eu/), which aims to facilitate the application of FAIR principles to data from certain IMI projects and datasets from pharmaceutical companies.

The ECBD is the central database for the integration of screening data from EU-OPENSCREEN projects with advanced search, analysis, and visualization tools. There will be three levels of data management and access: First, bioactivity data generation of compounds in screening projects, implemented at the individual EU-OPENSCREEN screening sites, using assays provided by the external collaboration partners; second, the integration of these screening datasets from partner sites into the ECBD; and, third, public dissemination of the data through established databases like ChEMBL [24] and PubChem [25, 26]. The ECBD is hosted by Petr Bartunek, the coordinator of CZ-OPENSCREEN, and his team at the Institute of Molecular Genetics of the ASCR in Prague, Czech Republic, who have developed the open data resource Probes & Drugs portal [27] as well as other databases such as the Zebrabase [28]. The e-infrastructure CESNET provides cloud-based hosting, backup and security.

An important aspect in the context of integrating complex and diverse screening data, when dealing with datasets from various affiliated, but legally independent sites that jointly use the compound collection, is the implementation of harmonized data standards and data curation. The ECBD adheres to well-established ontologies and identifiers, for example, the BioAssay Ontology (BAO) [29] for the classification and description of assays, which are commonly used by other similar open data repositories, such as ChEMBL or PubChem BioAssay. Only officially accredited partner sites have permission to upload data into the ECBD and uploaded data will be curated both automatically (e.g. file format, column values) as well as manually (e.g. data inspection) by the ECBD team. In case of ambiguities, the ECBD team contacts the data provider to resolve the issue. The ECBD team provides user support and help desk functions. Webinars on data deposition, the use of ECBD for data searching, visualizations and analysis are planned and dedicated workshops will be organized to demonstrate database users all ECBD capabilities and to share best practices in the community.

A grace period of up to 3 years between the completion of the primary screen and data publication in the EU-OPENSCREEN database is provided, during which the bioactivity datasets are not publicly accessible. This grace period allows for follow-up studies, publication in peer-review scientific journals and securing of intellectual property.

Assay development and screening facilities, and medicinal chemistry groups: EU-OPENSCREEN's affiliated screening partner sites implement the EU-OPENSCREEN high-throughput screening (HTS) and High-content screening (HCS) projects by using the EU-OPENSCREEN chemical compound collection, in collaboration with the external assay developer. They have been operational as local groups collaborating with external researchers over the past years, even before the EU-OPENSCREEN ERIC has been established. A recent publication showcases several successful projects, which have been realized by individual partner sites, as an example of the capabilities and expertise within the research infrastructure [20]. The chemistry groups have an excellent, proven track record in medicinal chemistry and hit-to-lead/tool optimization. As part of the collaborations with external researchers, they provide services ranging from the re-synthesis of hit compounds and chemical optimization by synthesis of focused libraries containing structurally similar analogues, elaboration of structure activity relationships (SAR), and NMR and TOF-LC-MS analytics.

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*Accelerating Chemical Tool Discovery by Academic Collaborative Models*

*2.4.2 Access to the research infrastructure for external researchers*

hit-to-lead/tool optimization, with an external chemist.

**Second**, organic and medicinal chemists and pharmacologists who seek to expose their compounds to a large number of screens, and thereby a wide range of biological targets. They provide their compounds to EU-OPENSCREEN, so that their compounds are 'bio-profiled' and tested as part of the screening collection at the EU-OPENSCREEN partner sites. As chemists often have only limited opportunities to systematically annotate their compounds, their incentive to provide their compounds to EU-OPENSCREEN is the possibility to identify novel biological activities of their compounds. A similar approach to crowd-sourcing academic compounds has been applied over more than a decade within the French Chimiothèque

main groups of researchers who will benefit from EU-OPENSCREEN:

The EU-OPENSCREEN partner sites have been operational as local screening platforms for many years. During this time, they predominantly work with their colleagues from the hosting institution and university. By working with the same collaborators over a longer time period, both sides could, over the time, increasingly gain practical experience and build a knowledge base, for example, in developing miniaturized, robust assays which are amendable to screening large compound collections. One of the aims of EU-OPENSCREEN is to enable as-yet under-served and under-represented user communities, which, by definition, did not yet have the opportunity to gain practical experience in these areas. Therefore, EU-OPENSCREEN will offer training courses, for example in assay development and other aspects of high-throughput screening. Furthermore, staff exchanges at established partner sites for scientists from prospective sites in countries that are not yet members of EU-OPENSCREEN promote convergence in technical capacities.

External scientists have open access to a chemical library, assay development and screening facilities, medicinal chemistry and informatics platforms. There are three

**First**, molecular and cell biologists, biochemists, microbiologists, plant biologists etc. who develop assays which are amendable to screening and are interested in developing a chemical 'tool' compound for their biological target or pathway of interest to answer a biological question or, in the case of disease-relevant targets, develop new therapeutic approaches to addressing unmet medical needs for patients. These scientists benefit from the open access to the screening capabilities of EU-OPENSCREEN's screening partner sites. They are encouraged to contact and consult the central office of EU-OPENSCREEN, which acts as a single point of contact for external scientists, prior to submitting a project proposal. Depending on the proposal and project requirements, the central office identifies one or more partner sites within the network, which offer the appropriate technology and expertise. The technical feasibility and scientific novelty will be evaluated. After the project proposal has been accepted, the project is initiated in collaboration with a partner site by transferring the assay onto the screening platform. This process often involves further optimization and miniaturization into a 384-well or 1536-well plate format, with the external scientist, who developed the assay, being actively involved in this process at the screening facility. After the screening of the EU-OPENSCREEN compound collection at the EU-OPENSCREEN screening site, data analysis and hit validation, a list with the validated hits will be available to the assay developer. The validated hits will be further optimized either with an EU-OPENSCREEN chemistry site or, if the assay provider already has an established collaboration for the

*DOI: http://dx.doi.org/10.5772/intechopen.91138*

*2.4.1.3 Training*
