Issue 101

Online Magazine of the European Molecular Biology Laboratory

Embracing the genome sequencing revolution

EMBL’s Genomics Core Facility provides end-to-end support to researchers across Europe and beyond and stands at the forefront of scientific breakthroughs.

Two male scientists in lab coats looking at.a computer screen
Vladimir Benes, Head of the Genomics Core Facility at EMBL Heidelberg and Jan Provaznik, Bioinformatician in the GeneCore team with the AVITI sequencer, the instrument used for genomic analyses, provided for testing within the framework of collaboration with Element Biosciences. Credit: Stuart Ingham/EMBL

DNA is essentially a long thread of genetic code that can be deciphered to access the fundamental instructions for life. In the late 1970s, British scientist Frederick Sanger developed a pioneering method for DNA sequencing – a breakthrough that earned him his second Nobel Prize in Chemistry in 1980. Ten years after this breakthrough, an international team of scientists set out to sequence all 3 billion letters of the human genome, launching the Human Genome Project. In 2003, two years ahead of schedule, the ambitious goal was reached, and the human genome was sequenced to 99.99% accuracy. By 2007, older sequencing technologies were supplanted by newer methods, collectively called next-generation sequencing, greatly expanding the scope of genomics research.

The EMBL Genomics Core Facility, also known as GeneCore, has lived through this revolution in the field of genomics. The facility started out in 2001 as a Sanger sequencing provider, under the aegis of biochemist Vladimir Benes, who still leads the facility today. Twenty-two years later, it has evolved into an advanced next-generation sequencing platform. 

The GeneCore team currently consists of five research technicians, three bioinformaticians, two senior engineers, and several visiting fellows and associates, who are dedicated to supporting researchers across EMBL’s member states. In addition to providing a wide array of advanced genomics services, the facility serves as a vital resource, facilitating groundbreaking research and fostering scientific innovation.

Two GeneCore staff members looking at a liquid handling robot.
Ferris Jung, Senior Engineer of NGS Automation and Laura Villacorta, Research Technician, with the liquid handling robot used for automated preparation of NGS libraries. Credit: Stuart Ingham/EMBL

At its core, the facility specialises in providing genomics technologies, with a primary focus on sequencing techniques. The platform is well-versed in the latest advancements, including what is commonly referred to as next-generation high-throughput sequencing or more accurately, massively parallel sequencing (MPS).

“The GeneCore team provides a complete service, from library preparation to sequencing. Beyond the regular services, Vladimir and colleagues are also helpful in developing methods where none exists,” said Ramesh Pillai, Professor at the University of Geneva, Switzerland, and one of GeneCore’s users. 

Another strength of GeneCore is its significant reach within the scientific community in EMBL’s member states. This vast network of users underscores the facility’s importance and its role as a central hub for genomics research. “We are here to help people flourish in their genomics projects, and this is an element which we believe makes us stronger as a service facility,” said Benes.

A female researcher looking at an illumina sequencer.
Daphne Welter, Research Technician monitoring the performance of the Illumina sequencer analysing NGS libraries. Credit: Stuart Ingham/EMBL

Enabling diverse user projects – from COVID-19 to the flu virus

Over the course of its two decades in operation, GeneCore has made significant contributions to a diverse range of projects. 

In 2020, following the outbreak of COVID-19, scientists sequenced the genome of the SARS-CoV-2 virus, creating a significant impact on the global response to the pandemic. GeneCore played its part here, both in the development of tests for diagnostics and in the monitoring of variants. “When the pandemic reached us, we were able to pretty quickly set up testing schemes for EMBL,” said Benes. “We also participated in the sequencing of positive samples from PCR analysis for the identification of SARS-CoV-2 variants of concern. And even there, we were prepared, which is one of GeneCore’s assets.”

Another example is a long-standing collaboration with Stephen Cusack, former Head of EMBL Grenoble, who has been studying the influenza virus for more than 30 years, contributing to one of the most detailed descriptions of the influenza virus’s RNA polymerase. “Cusack’s group created an artificial system to unveil the influenza virus polymerase function, which needed sequencing experiments to be verified,” said Benes. “They came to us and we helped them solve it. We make sure to take on every project with the same degree of commitment.”

Two female scientists seen from above using a high-resolution electrophoresis Femto instrument
Hilal Ozgur and Mireia Osuna Lopez, Research Technicians in the GeneCore team, using the high-resolution electrophoresis Femto instrument to check the DNA samples’ integrity prior to their processing for long-read sequencing. Credit: Stuart Ingham/EMBL

“The GeneCore team has played a central role in advancing the success of my PhD project, notably by establishing tailored capture protocols to investigate the structure of the inactive X chromosome,” said Antonia Hauth, PhD student in the Heard Group at EMBL. “It is invaluable to have such experts at EMBL, whom we can always directly reach and who have extensive expertise in many (if not all) sequencing-based experiments you could wish for.”  

GeneCore manages an impressive volume of samples, with approximately 20,000 currently in its care, encompassing both physical specimens and data. Of these, a remarkable 10,000 samples undergo various processing methods to make them suitable for sequencing, underscoring the facility’s dedication to advancing genomics within the EMBL research community.

Democratising model organism research and handling data

Genomics technologies have advanced significantly in recent years, becoming increasingly faster and more efficient. Modern sequencers, like those based on Illumina’s technology, can generate millions to billions of DNA sequences in a single run, producing terabytes of data in a matter of hours. As of today, some of the fastest high-throughput DNA sequencers can sequence the DNA of a human-sized genome (approximately 3 billion base pairs) in a matter of hours to a day. 

“We get every kind of organism, from all sorts of bacteria, fish, mice, and human samples. A couple of years ago the concept of model organisms was very biased due to their historically accessible features. With sequencing, you can have your own model organism” said Benes. “Next-generation sequencing has, in a way, democratised this space, by opening up access to the primary information which every organism has – the genome.” 

Beyond the provision of cutting-edge technology, GeneCore actively assists researchers in taking their genomics projects to completion, ensuring they receive the guidance and support needed for success. With an end-to-end service, the facility guides the users from the experimental design to the final data analysis and interpretation of results.

“Genecore has helped me to fully understand the technicalities behind my sequencing projects and this has greatly improved the quality and throughput of my work,” said Carlos Voogdt, EIPOD Postdoctoral fellow in the Zimmermann, Typas, and Zeller groups. “With their expertise and patience, they are also assisting us in the generation of high-quality whole-genome sequences of hundreds of bacterial strains.”

“The dedication of the Genecore Team leads to high-quality data that is fundamentally supporting our research questions,” said Matthias Groß, Research Technician in the Zimmermann Group at EMBL Heidelberg. 

GeneCore also supports scientists in managing the impressive data volumes that come out of sequencing experiments – one single DNA sequencing run can produce data comparable to the amount of text found in more than 1 million average-sized novels, assuming each base sequenced corresponds to a letter in a book.

“To date, GeneCore has generated more than 100 terabases of MPS sequence data for its users,” said Benes. “Such data volumes can be overwhelming, and for sure, we need to interpret them, and this requires a very intimate interaction with the users. That’s why GeneCore is also equipped with computational biologists and bioinformaticians. On top of that, we also train the users to interpret their own data. It’s one of GeneCore’s priorities to provide guidance throughout experiments.”

Four sequencing machines inside the GeneCore facility
GeneCore sequencing room, with Illumina Sequencers running; their powerful suite provides users with adequate flexibility and throughput to meet their needs timely. Credit: Stuart Ingham/EMBL

Looking ahead: the future of genomics

According to Benes, genomic sequencing of cancer cells is one of the key topics destined to be more and more relevant in the future. “There’s no question that genomics will help substantially in cancer research. There are also many other diseases with genetic underpinnings, and sometimes the detail is incredibly small – like single base mutations in the DNA. This is not very easy to find, and GeneCore helps find these tiny hallmarks in genomes,” he said. “The refinement of sequencing methods will also continue to advance rapidly.” The facility is also poised to provide significant support for TREC Traversing European Coastlines (TREC), the flagship project of EMBL’s Planetary Biology transversal theme.

“We’re seeing TREC samples coming into the facility already,” said Benes. “Our contribution to the project revolves around single-cell transcriptomics and DNA barcoding.” For example, in collaboration with Flora Vincent, Group Leader at EMBL Heidelberg, the GeneCore team helped optimise the method for direct DNA barcoding, eliminating the need for DNA isolation. 

Furthermore, working alongside Rainer Pepperkok, Director of Scientific Core Facilities and Services, EMBL, and Johan Decelle, Junior Group Leader at CNRS, the team will be spearheading single-cell transcriptome analysis.

“The GeneCore team is also putting great effort into reducing waste as much as possible,” said Groß. “Their offer to share a number of instruments and train users for those could serve as a role model for many other institutes all over Germany to become more sustainable.’

In a time defined by extraordinary progress in genomics and its maturing tools, Benes and the GeneCore team at EMBL will continue to shape the way we think about science and address global challenges.

“Sequencing always brings the element of surprise, as it often uncovers unexpected findings, and this sense of discovery is what makes running the platform so exciting,” concluded Benes.

Tags: core facility, genecore, genomics, services, single-cell genomics

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