Nowadays biological research heavily relies on the application of “omics” technologies. In particular, Next Generation Sequencing (NGS) methods have completely changed the face of omics technologies and their application.
NGS enables a host of omics analyses (genomics, transcriptomics, epigenomics, metagenomics, immunogenomics, etc.) at unprecedented resolution, speed, depth and at low cost compared to the previous generation of technology (the initial sequencing of the human genome that finished just 15 years ago cost in excess of 1 billion $, while NGS-based methods today do the same for around 1,000 $). This allows performing many experiments we could only dream of less than a generation ago.
However, modern omics operations require high up-front investments, highly specialized expertise, and a high degree of integration of different elements, such as elaborate experimental design, laboratory techniques and automation, tracking systems, computational environments, data analysis, bioinformatics, and quality management systems.
As such it is obvious that having infrastructures that hold this expertise and that put it at the service of the research community is a preferable model over sub-critical-effort operations. Building NGS infrastructures with all the required know-how is challenging and maintaining them at the forefront is costly.
A model where hubs offer access to state-of-the-art, well-maintained facilities makes economic sense, and several European countries have taken the path of establishing a national infrastructure.
These national infrastructures are united in EASI-Genomics.
The mission of EASI-Genomics is to provide easy and seamless access to cutting-edge DNA sequencing technologies to researchers from academia and industry, within a framework that ensures compliance with ethical and legal requirements, as well as FAIR and secure data management.
The EASI-Genomics consortium has directly evolved from the ESGI (European Sequencing and Genotyping Infrastructure – EU FP7 2007-2013 Infrastructure Project, project number 262055). Eight ESGI partners are now members of this consortium, while another eight partners with complementary expertise have joined EASI-Genomics and can help the former joint infrastructure reaching the next level in its implementation. ESGI allowed the creation of a community that shares procedures, harmonizes methodology and exchanges experience.
In ESGI we learnt that the service offered by an infrastructure has to go beyond the mere provision of raw data. For this reason, we plan to extend the breadth of support of access projects from study design to analysed results and to a substantially larger number of users than before. Users will not just receive a service but will be included in the whole process and thus be trained in all the steps of the study. Several of the partners have been working towards this in recent years, so that we are now in a perfect position to provide such comprehensive support to access projects.
The community is in urgent need of good standards, in particular for data analysis. Another need is efficient computational frameworks for data analysis. EASI-Genomics will work on these requirements and will develop tools that can be deployed widely, so that smaller operations can be established without the need to build large computing facilities.
By implementing its objectives, the EASI-Genomics project aims to build a community of practice which leverages advanced sequencing technologies beyond country and sector borders to tackle global challenges in science.
EASI-Genomics is user-oriented and all its objectives are aligned to provide excellent services, which precisely respond to the requirements of academia and industry. Thus, EASI-Genomics will establish a dialogue with, and promote collaboration among the different stakeholders to identify needs, existing gaps and opportunities. Especially the two sectors, academia and industry, will learn and benefit from each other throughout the project. By giving a significant number of users access to the best technologies in high-throughput genomics, EASI-Genomics will contribute to the impact that European Research and Innovation activities bring to the competitiveness and growth of its companies, and to other important benefits for its citizens (e.g. health, agriculture, biotechnology).
The main objectives of EASI-Genomics are:
- Culture synergy between European genomics infrastructures and create a wider co-operating community between all stakeholders
- Provide access to integrated state-of-the-art high-throughput DNA sequencing infrastructures to the European research community
- Benchmark and harmonize NGS and data analysis methods
- Establish standards to ensure quality, accessibility and reusability of produced data
- Develop new and better techniques for both pre-analytical and analytical methodologies in NGS
- Train researchers in NGS technologies to enable them in the best use of European Research Infrastructures and to foster innovation capacity
Our consortium joins sixteen partners from eight different EU member states. It includes eleven of the largest genomic facilities in Europe, which will provide access to their services and develop new methods and standards. In addition, some partners are experts on ethical, legal and societal implications, data management, and/or method harmonization. The consortium also includes two industrial partners that develop relevant methods and tools, and have extensive involvement in setting standards for pre-analytical and analytical procedures.
EASI-Genomics consortium is coordinated by Ivo Gut (CNAG-CRG), assisted by the Project Management Team. Day-to-day follow-up and operational decisions are the tasks of the Steering Group (work-package leaders) while decisions on major changes need the approval of the General Assembly (all beneficiaries). The consortium gets expert guidance from its International Scientific Advisory Board (SAB). Transnational Access activities are coordinated by Sascha Sauer (MDC) and Ann-Christine Syvanen (Upsala U).
McGill University (CA)
Sanger Institute (UK)
New York Genome C (US)
Access Project Manager
EASI-Genomics objectives and activities are all oriented towards the creation of a long-lasting community of practice and the provision of excellent access to the integrated infrastructure nodes for academic and industrial users. The work plan reflects this overarching goal. As a consequence, the work plan is organized around Transnational Access, ans structured in the following eight activities:
Emmanuelle Rial-Sebbag (INSERM)
This framework provides crucial elements of guidance for Transnational Access, both to providers and users. It ensures that data is procured according to legal, ethical and societal standards. Moreover, this framework guarantees that data is stored and maintained securely, and is findable, accessible, interoperable and reusable.
Sascha Sauer (MDC) and Ann-Christine Syvänen (Uppsala U)
Four calls for access are organised during EASI-Genomics.
Each call will focus on several topics: de novo assembly and annotation, rare diseases, inflammatory diseases, single-cell analysis, cancer, functional genomics, etc. Through a rigorous peer-review process involving external reviewers, the best project proposals are identified. Each selected access project receives support regarding study design, sample preparation, sequencing, primary data analysis and, importantly, also interpretation. Support covers the entire value chain of a sequencing-based analysis at state-of-the-art facilities with world-class setups and focused expertise.
The catalogue of experiments that the infrastructure nodes can cater for are: Whole-genome sequencing (single-cell, multi-cell and cfDNA (cell-free DNA)); targeted re-sequencing (exome, mutations, SNVs, CNVs); epigenetic analysis (RRBS, whole-genome bisulphite-seq, whole-genome oxidative bisulphite-seq, HiC-seq, ATACseq); RNA-seq; single-cell, CROP-seq, in situ sequencing; microbial sequencing and HLA sequencing. We also offer Nanopore, PacBio and 10x Genomics sequencing, and are preparing optical mapping techniques. These techniques are particularly important for de novo assembly and tumour genome analysis. Nanopore sequencing can be used for direct sequencing of RNA and direct analysis of DNA modifications.
Each experiment is executed using best-in-class methods supported by SOPs and backed up with dedicated data analysis pipelines. In function of the expertise required by an access project, parts of it might be carried out at different infrastructures. In total, we expect to provide more than 100 Terabases of sequencing, and 25,000 hours of support for study design, bioinformatics analysis, support and training to an estimated 150-300 access projects.
Ivo Gut (CNAG-CRG)
Methods for sequence analysis are still evolving and require continued adaptation by the infrastructures. Methods used by multiple EASI-Genomics infrastructures, are aligned to a best-in-class version. This covers wet-lab procedures, computational methods used for data analysis, and the methodology used for deposition of data.
Project-wide benchmarks for DNA, RNA, and epigenetic analyses are being organised. Participation in the creation of these benchmarks is also offered to external facilities (e.g. core facilities). A major effort is focused on the development of standards in alignment with the Global Alliance for Genomics and Health. These outputs will provide community standards and a framework for accreditation. Eventually these will improve the quality of sequencing at the community level.
Christian Conrad (Charité)
EASI-Genomics implements new technologies that are of interest to the scientific community, specifically developing new laboratory and computational methods. The goal is to maintain the EASI-Genomics infrastructures cutting-edge, attractive, and competitive in the rapidly evolving genomics landscape, allowing the scientific community to get access to new state-of-the-art technologies. The updating process is based on the study of user needs on the one hand, and the detection of new technologies potentially covering those needs on the other.
The key drivers for technology implementation are:
- increase size of sequenced fragments to ameliorate accurate mapping and eliminate statistical inference
- decrease project running time both in the laboratory and in the analysis of data
- process all types of samples of very low quantity
- allow portability of technology to allow sequencing in various conditions.
Newly implemented technologies will be eventually integrated into the activities on harmonization and benchmarking.
Jean-François Deleuze (CNRGH)EASI-Genomics will investigate wet-lab techniques for developing and supplementing novel sequencing-based techniques in order to provide them for future access. Eventually wet-lab developments will be combined with the development of new computational methods. Whenever appropriate, new methodologies will be implemented, included in harmonization and benchmarking and eventually in EASI-Genomics Access offer . Finally, exploitable outputs will be protected and assessed for their innovation potential, or directly disseminated and shared with the community.
Matthias Schlesner (DKFZ)
EASI-Genomics carries out research on computational and data analysis methods matching the developments in NGS-based techniques. These outcomes are aligned with wet-lab developments and will be deployed for implementation, standardization and eventually access. Dissemination and exploitation will be seeked as adequate.
Kurt Zatloukal (MUG)
Transnational Access calls are designed to inssure international and inter-sectorial reach and to promote the selection of excellent projects. They promote the community uptake of new and selected standards, tools and concepts.
We reach out to the different stakeholders to transfer knowledge and consult with them about their future needs and interests. We develop and organise workshops and seminars to train the new generation of users.
A new community platform has been created, as a meeting point where users, providers, suppliers, but also funders and policy makers can exchange information about challenges and opportunities. In addition, EASI-Genomics promotes the generation of Expert Centres, as public-private partnerships to support innovation and sustainability.
Ivo Gut (CNAG-CRG)
Internal communication within the consortium is coordinated by CRG. The coordinator manages the project by overseeing activities, identifying risks, and solving potential issues. It ensures that the project achieves all technical and scientific objectives within the assigned time frame and budget at highest quality.
The joint research in EASI-Genomics has the objective to augment the methods and processes that can be offered for Transnational Access.