Meeting report: Functional Genomics and Proteomics – Applications, Molecular Diagnostics & Next Generation Sequencing

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The Functional Genomics and Proteomics meeting, which evolved from the Status Seminar Chip Technologies, is an annual event held in early February at the DECHEMA-Haus in Frankfurt, Germany. This year's meeting was held on two particularly cold days (February 2-3, with –10°C / 14°F temperatures). The meeting consisted of two plenary lectures; 17 premier oral presentations – selected from the submitted abstracts based on their “scientific interest level, ” according to chairman of the scientific organizing committee, Dr. Jörg Hoheisel (German Cancer Research Center – DKFZ, Heidelberg, Germany); 53 poster presentations; and an accompanying exhibition with 19 companies. The meeting also continued its tradition of having a panel discussion at the end of the first day, which was again a highlight of the event – this time on the “facts and fiction” of systems biology.

Next-generation cancer therapy

According to the World Health Organization, cancer is a leading cause of death worldwide. It is an existing challenge that is likely to be further exacerbated as the population ages throughout the world. It is therefore fitting that many of the presentations at this year's meeting focused on identifying new drug targets and biomarkers using various novel approaches.

“Genome sequence analysis is like drinking out of a fire hose, ” with this introductory sentence accompanied by equally captivating images, Prof. Stefan Bohlander (Marburg University, Germany) shared with the audience results on identifying somatic mutations in acute promyelocytic leukemia (APL) by exome sequencing, an approach that is much more technologically and economically viable than whole genome sequencing (for detailed information, see [1]).

“Genome sequence analysis is like drinking out of a fire hose”

Other approaches included, for example: Helen Hülsmann's (DKFZ) reverse-phase-protein-arrays to identify response markers to chemotherapy in non-small cell lung cancer (NSCLC); large-scale combined proteomic and gene expression analysis for breast cancer as reported by Dr. Jan Budczies, (Charité – University Hospital Berlin, Germany); and shRNA/RNAi screening to identify novel targets in the treatment of pancreatic cancer reported by Johannes Fredebohm (DKFZ).

Linking genome-wide screening protocols with personalized medicine approaches remains a challenge. Dr. Christian Schmees (University of Tübingen, Reutlingen, Germany) presented their novel platform technology that allows for individualized transcriptome-wide functional analysis with enzymatic generation of transcriptome-based (ENTRACE) shRNA libraries, which is currently applied to primary renal cancer cells.

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Other applications of genomics/proteomics

Functional genomics and proteomics are, of course, not for cancer research alone. As demonstrated by several speakers, these approaches have wide applicability, such as in understanding differentiation of embryonic stem cells to cardiomyocytes (Lin Gan, RWTH Aachen University, Germany) and in the validation of biomarkers associated with autoantibodies involved in autoimmune heart failure (Prof. Roland Jahns, Würzburg University Hospital, Germany).

An industrial perspective of functional genomics and proteomics

In addition to the presentations from academia, industry presenters also made a strong appearance at the meeting. Dr. Christopher Pöhlmann from Bruker Daltonik, shared with the audience their “portable toxin detector”, which offered several advantages over traditional technologies. Dr. Klaus Dücker from Merck Serono, discussed the challenges in validating biomarkers from a pharmaceutical industry's perspective and highlighted the importance of checking for antibody specificity before drawing any conclusions. Dr. Peter Schulz-Knappe from Protagen presented their work on biomarker identification in various disease settings, using a systematic high-throughput and high-content analysis of the immune-proteome. Dr. Janet Schache from Merck Millipore, shared with the audience the challenges in drug development and highlighted the need to obtain toxicology results early in the process. Using the multiplex bead-based Luminex xMAP(r) technology, it is possible to obtain rapid and automated analysis of drug effects on key parameters such as protein synthesis and stress response.

Systems biology – fact or fiction?

This year's panel discussion theme, “Systems biology – fact or fiction”, was hotly debated by a panel of experts. Following a brief introduction from Prof. Martin Hrabë de Angelis (German Research Center for Environmental Health & TU Munich, Germany) to set the scene, Prof. Rudi Balling (University of Luxembourg) put forward his opinion that systems biology is here to stay, although there are both factual as well as fictional aspects to the current state of systems biology. Fact, in the sense that complex data sets can no longer be meaningfully interpreted without mathematics; and fiction, in the sense that the analysis is no way at a predictive stage. Prof. Balling also calls for more physicist and mathematicians to work with biologists to address complex biological questions. Dr. Jörg Hoheisel concurs that systems biology is required to understand biology, but disagrees with regards to what is fact. While we have lots of data, we need a lot more to be able to describe systems, as highlighted by new substitutions for the methyl group in 5-methyl-dC or the unknown function of the very large number of non-coding RNAs, for example; also, protein-interactions are far from being known quantitatively, let alone aspects such as time and localization in space. Also, the infrastructure is missing to deal with this vast amount of data, as is a cohesive strategy. Along these lines, Prof. Thomas Werner (Genomatix Software GmbH) confirmed that we are indeed at the stage of systems analysis but not quite at systems modeling, and Prof. Siegfried Neumann (TU Darmstadt, Germany) also emphasized our need for quantitative analysis.

While the panelists may not have had agreed on every aspect of the discussion, they did concurr that a bioengineering approach contributes greatly to our understanding of biology, and were all admirers of Prof. Doug Lauffenburger's work, i.e. his engineering approaches uses every approach available in the mathematical tool box to address various biological questions (for an example, see [2] in this issue of Biotechnology Journal). Another important aspect is that of education and collaboration, i.e. current university curricula select for mathematics-averse biologists and perhaps also biology-averse physicists, when instead these subjects are required to fully comprehend the complex nature of biology and highlights a need for true “bioengineers” and collaboration between the disciplines.

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Plenary Lectures

This year's two plenary lectures were presented by Prof. Jörn Walter (Saarland University, Saarbrücken, Germany) and Prof. Ivo Gut (National Genome Analysis Centre, Barcelona, Spain). Both were enlightening as well as entertaining for the audience.

Prof. Walter's presentation “The dynamic of epigenomic landscapes in development and disease”, focused on work that is part of the International Human Epigenome Consortium (IHEC, http://www.ihec-epigenomes.org/), and covered two major aspects of epigenetic control by DNA-methylation, including the dynamics and mechanisms underlying resetting of epigenetic information during early phases of development, and the latest developments in analysis of DNA-methylation patterns using next-generation sequencing.

Prof. Gut's presentation “High resolution whole genome analysis and cancer”, described Spain's contribution to the International Cancer Genome Consortium (ICGC, http://www.icgc.org/) on the genomic details of chronic lymphocytic leukaemia [3]. Prof. Gut also discussed another project, the IT Future of Medicine (ITFoM, http://www.itfom.eu/), which is an EU-funded pilot action in the Future and Emerging Technologies (FET) Flagship Scheme that aims to create computer models of humans that are tailored to the individual. While life-expectancy has continued to rise over the past few decades, the actual healthy life-expectancy remains at about 60 years of age. The goal of the project is to revolutionize the way we approach healthcare and to keep each one of us healthy for longer.

ITFoM seeks to create computer models of humans that are tailored to the individual

Poster awards

Last but not least, three posters were selected as the best posters, based on their presentation of “novel methods with different, but not always obvious approaches, ” according to Prof. Thomas Joos (Tübingen University, Reutlingen, Germany), one of the judges on the panel. The three winners each received a cash prize of 300 Euros: Alexander Groß (Ulm University, Germany) for “A delay-differential equations model for irradiation-induced differentiation across subpoplulations of hematopoietic stem cells”; Jonas Wolf (DKFZ) for “A RNAi screen in tumorspheres identifies genes important for self renewal of breast cancer stem cells”; and Julia Schanda (Georg-Speyer-Haus, Institute for Biomedical Research, Frankfurt, Germany) for “From structure and 3D-design to the rational development of specific inhibitors against leukemia”.

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Final words

From its early days as a microarray meeting more than a decade ago, to its current focus on functional applications of genomics and proteomics, this meeting has evolved continuously to meet the demands of its core audience. This year's meeting, with its excellent talks and poster presentations, as well as a most intellectually stimulating panel discussion, again highlights the relevance of the meeting. It is anticipated that the next incarnation of this meeting will be equally, if not more, exciting and full of the latest developments and innovations.

Judy Peng, PhD., Managing Editor, Biotechnology Journal

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