Next Generation Sequencing
29 August - 1 September 2010
Leiden, Netherlands

Organisers:

Draft Report

Summary

Next generation sequencing (NGS) technologies enable high-throughput sequencing for a multitude of applications, including de novo sequencing, re-sequencing of (subsets of) genomic DNA, whole transcriptome sequencing, tag-based transcript sequencing, and metagenomics sequencing. There has been active research in these and other NGS applications resulting in a rapidly developing field. While the second-generation technologies are being further improved, third-generation sequencing is already becoming available and utilized by pioneer researchers. However, because of the rapid developments, many scientists, some just considering the use of NGS technology, have a need for information and sharing of experiences. Furthermore, recent results show applications emerging in fields that are not immediately obvious, including evolution, environmental, forensics and archeology.

Supported by a grant from the the ESF Programme in Functional Genomics, we brought together international experts in the field to present their work and share their experiences with European researchers. The focus was mainly on the applications of high-throughput sequencing to accelerate research on evolution, gene expression and regulation, as well as biomedical and diagnostic applications. Invited and selected talks were complemented by poster and hands-on sessions. The scientific meeting accelerated the diffusion and exchange of information among European researchers, including those from labs where NGS is not yet being used.

About two-thirds of the participants (112) were based in The Netherlands, the remaining 57 participants came from Europe (47) and the rest of the world. We received 37 abstracts. In addition, we had 21 sponsored participants and 24 invited speakers, workshop leaders and members of the scientific committee. A total of 214 people attended the conference.

Scientific Content

The topics chosen for the meeting sessions were mainly focused on human genetics research, and included research on model organisms and more technology/ bioinformatics-focussed talks. The session “From old to new: evolution and archaeology” showed the acceleration of research into evolution and migration, and even climate, by next-generation sequencing. “Gene expression and regulation” was a large session with stimulating talks on mRNA, miRNA and transcription factor binding site NGS projects. The largest session was on “Re-sequencing and diagnostics” and illustrated the power of NGS to identify disease-causing mutations, and indicated successes as well as pitfalls and future directions. The session on “Current and Future Challenges” had diverse bioinformatics talks including read alignment and data storage, standards for NGS data. The final afternoon featured two “New Technology Talks” sponsored by Fluidigm and Life Technologies, as well as a discussion chaired by Thomas Gübitz from the FP7 project ERA-Instruments.

Assessment of the results & impact of the event on the future direction of the field

Next-generation sequencing (NGS) has many applications in genetics and molecular biology. This meeting gave a good overview of obvious, but also surprising, possibilities of NGS. One of the strengths of the meeting, in addition to it's early timing, was the broad scope ranging from metagenomics, ancient genomes, and model organisms, to Mendelian diseases. The attractiveness of the meeting was shown by the willingness of internationally renowned researchers to give an invited lecture, which made for an excellent scientific programme. In addition, we managed to attract many young researchers, with PhD students making up around 25% of the total number of participants. Key in attracting young researchers was the low registration fee and the special Young Researchers' programme, giving ten young researchers the opportunity to give a talk, as well as pay more attention to their work with poster and oral presentation awards.

Especially for diagnostics of Mendelian disorders, several speakers demonstrated the maturity of the method to identify disease-causing mutations based on exome re-sequencing of a well-defined set of patients. It became clear that it is very important to filter out non-causal variation and technical artifacts. Different speakers concluded that the best filters use variation found in sequencing data from other genomes analyzed by the same group, as well as a conservation score per base indicating evolutionary constraints. Debbie Nickerson from the University of Washington, on her way to analyse and make public a 1000 exomes, called finding the disease gene for a recessive disorder, “a walk in the park”. Going to the next level, several succesfull examples for finding disease genes for autosomal dominant syndromes were shown. Key to success, not surprisingly, is precise phenotyping to increase the chances that the studied patients carry mutations in the same gene. It will take a world-wide effort to identify the causal variant in all Mendelian disorders. More challenging routes lay ahead to apply this approach to diseases with more complex genetics. To use the analogy from Edwin Cuppen, Hubrecht Institute and University Medical Center Utrecht, The Netherlands, to find the few functional and causal polymorphisms among the many millions of variants between a patient and the reference genome is like “searching for Wally (Waldo)”.

In a technology-driven field such as NGS, it is important to keep up to date with new developments that could improve the speed, accuracy, and possibilities of sequencing.

Outlooks to the “next of NGS” were given by Ivo Gut, touching upon 4 generations of nucleic acid analysis including nanopore sequencing, and in a sponsored talk from Raimo Tanzi on quantum-dots. We would have liked to feature more new technology talks on third-generation sequencing, but most of these new companies were not able to sponsor a scientific speaker.

While the outlook to the future showed that there are newer technologies being developed to sequence more and better, it is important to solve and disseminate the data analysis problems of today. There was much interest in the hands-on workshops where participants learned to work with different EBI resources and with  Leiden University Medical Center / Netherlands Bioinformatics Centre's NGS data analysis pipelines in Galaxy.

While several more topical NGS meetings are being planned in Europe, and for example the Benelux has it's yearly NGS user meeting, this general European meeting may be held again in two years time to bring together the broad NGS community and have interactions across research disciplines and fields. It may be considered to include more non-biomedical/human genetics speakers, such as those from plant or micro-organisms NGS projects.