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High-throughput technologies and bioinformatics from a single source – the Quantitative Biology Center (QBiC)

“Omics” is a current buzz word used to describe comprehensive investigations in many areas of the life sciences. In practice, omics refers to fields of scientific study that involve a huge number of experiments and even more data. Evaluating and managing all the data within a fixed period is a huge challenge for most researchers working on their own. It was to address these issues that the Quantitative Biology Center – QBiC for short – was established at the University of Tübingen in 2012. To date, the QBiC is the only bioinformatics core facility in Germany. It offers scientists from different disciplines support in carrying out all types of high-throughput analyses. The centre is also the only one that provides professional support from initial planning of experiments to final analysis.

Dr. Sven Nahnsen, bioinformatician and biotechnologist, has been head of the Quantitative Biology Center in Tübingen since 2012. © QBiC

The scientists at the Quantitative Biology Center (QBiC) in Tübingen call their institution a "one-stop shop" - with good reason. The QBiC was set up to help life sciences researchers perform high-throughput experiments from start to finish – offering support in initial project planning right through to final analysis and interpretation of data, all from a single source. Once the materials and methods required for a specific project have been determined, all a QBiC client has to do is return the barcode-labelled samples. The computer scientists and bioinformaticians at the QBiC, in close cooperation with scientists from member institutions, then analyse the samples, and annotate and integrate the resulting data. QBiC clients can follow the progress of their data on a dedicated central web portal that gives access to processed data, and where researchers can request reinvestigations.

The core facility is available to internal and external scientists, and was established at the University of Tübingen in 2012 with funds from the German Excellence Initiative in cooperation with the University Hospital and the Max Planck Institute for Developmental Biology. It is the only one of its kind so far in Germany.

The idea of offering bioinformatics tools to analyse data produced with high-throughput technologies as a service to researchers, was developed at the Centre for Bioinformatics at the University of Tübingen around three years ago. Professor Oliver Kohlbacher was instrumental in the establishment of the QBiC, and Dr. Sven Nahnsen was the first scientist at the QBiC. Nahnsen is a bioinformatician, biotechnologist and head of the centre. Today, the centre's core team consists of ten additional computer and bioinformatics specialists who are responsible for project management and data analysis. Biological samples are analysed at one or several of a total of ten QBiC member institutes such as the Max Planck Institute for Developmental Biology, the Proteome Center Tübingen (PTC) and the Medical Proteome Center at the University of Tübingen, the Institute of Medical Genetics and the Centre for Plant Molecular Biology (ZMBP).

The only thing clients have to do is provide the samples

"The idea behind the QBiC was to bring together the large-scale omics experiments (genomics, transcriptomics, proteomics and metabolomics) performed at different institutes in Tübingen with data management, analysis and interpretation," says Nahnsen. Back in 2012, Tübingen already had excellent core facilities that generated high-throughput data and where individual experiments generated a large amount of data. However, manual analysis of data generated by so-called multi-omics experiments (the parallel acquisition of different omics data from one and the same sample) is no longer feasible due to the sheer quantities of data generated, no useful information can be derived from such experiments. In many research projects, complex data analyses are very promising, but many scientists are simply unable to handle such huge amounts of data.

Nahnsen adds: "On the one hand, biologists and medical doctors need the support of bioinformaticians like ourselves at the QBiC. On the other hand, it is equally hard for bioinformaticians to do the job on their own. This is because they do not have the metadata, i.e. the basic information about the data to be analysed, which they need to be able to discover relevant information. It was to bring these two groups together that the QBiC was established. Scientists can come to our one-stop shop at a very early stage in their work, for example at the experiment planning stage. An interdisciplinary team will then collect all important metadata. We send customised barcodes to the client, the client then labels the samples and sends them to us. We distribute the samples to our member institutions and the data generated will be stored on our servers. We have written some of the software programmes ourselves, as well as adapting existing solutions to our requirements."

The data are generated at QBiC member institutions using next-generation sequencing or mass spectrometry. These institutions have the necessary equipment and expertise to perform complex investigations of this kind. The resulting data are then collected at the QBiC. "This organisational structure also enables us to perform multi-omics experiments," says Nahnsen. Data management and analysis are done using the QBiC central web portal that project participants can log in to at any time. The portal is very user-friendly. "Our aim was to train the users of our services, so that they would all know how to look at high-throughput data," says the head of the QBiC, going on to add: "Our national unique selling point is that, together with our member institutes, we offer outstanding expertise in any high-throughput technology whatsoever, whether it be genomics, proteomics, transcriptomics, metabolomics, biometrics or statistics."

Big Data on high-performance computers and storage units

Powerful computers and disk space is available for the data that the QBiC receives. Bioinformatic analyses are carried out exclusively on copies, the original data are stored unchanged. © QBiC

High-performance computers and high-performance disk storage units at the Centre for Data Processing at the University of Tübingen deal with the huge amounts of raw data that the QBiC receives, annotations, connotations and integrated analyses. Nahnsen refers to data from omics experiments as Big Data. "Just imagine, the data of one patient in a biomedical research project we are currently working on need several hundred gigabytes (1011 - 1012 bytes) of storage space," says Nahnsen.

Raw data from the experiments are immediately stored in the archive. All bioinformatics analyses are made with copies to ensure that original data are safely stored and not lost. "We store data at a central place, but scientists always have access to their data. We use special bioinformatics analysis workflows to reduce the large amounts of data to the most essential. The software we use for this purpose is always kept up to date," explains Nahnsen.

Most of QBiC's orders are from scientists at the University of Tübingen and QBiC member institutes. However, QBiC services are also available to external academic and industrial institutions. Most experiments can be carried out quite quickly. Normal sequencing experiments have a handling time of four to six weeks. However, the analysis of entire genomes takes quite a bit longer.

Omics projects are thoroughly planned and discussed by interdisciplinary QBiC teams. Metadata are collected and barcodes for sample-labelling are generated. © QBiC

Driving automation forward

However, the QBiC does more than just help scientists perform high-through experiments; it also carries out its own research projects. "We are involved in methodological research and the development of bioinformatics methods," says Nahnsen. One major focus area of the QBiC scientists is the automation of data management and analysis, along with the development of new database concepts designed to make omics experiments even more efficient. QBiC bioinformaticians are also involved in a number of cooperative biomedical research projects, including the BMBF-funded project e:Med Multiscale HCC. The QBiC will play a part in the Centre of Personalised Medicine that is currently being established by the University and University Hospital of Tübingen.

In view of all the new projects, Nahnsen is seeking to expand his team in the foreseeable future: "We need to grow to meet demand, but it all depends of course on how much money we have available for this." He adds: "We also want to drive forward the automation of the process. But this can only be achieved up to a certain point."

Website address: https://www.gesundheitsindustrie-bw.de/en/article/news/high-throughput-technologies-and-bioinformatics-from-a-single-source-the-quantitative-biology-center-qbic