Cell-free tumour DNA analysis detects copy number alterations in gastro-oesophageal cancer patients.

BACKGROUND: Analysis of cell-free tumour DNA, a liquid biopsy, is a promising biomarker for cancer. We have performed a proof-of principle study to test the applicability in the clinical setting, analysing copy number alterations (CNAs) in plasma and tumour tissue from 44 patients with gastro-oesophageal cancer. METHODS: DNA was isolated from blood plasma and a tissue sample from each patient. Array-CGH was applied to the tissue DNA. The cell-free plasma DNA was sequenced by low-coverage whole-genome sequencing using a clinical pipeline for non-invasive prenatal testing. WISECONDOR and ichorCNA, two bioinformatic tools, were used to process the output data and were compared to each other. RESULTS: Cancer-associated CNAs could be seen in 59% (26/44) of the tissue biopsies. In the plasma samples, a targeted approach analysing 61 regions of special interest in gastro-oesophageal cancer detected cancer-associated CNAs with a z-score >5 in 11 patients. Broadening the analysis to a whole-genome view, 17/44 patients (39%) had cancer-associated CNAs using WISECONDOR and 13 (30%) using ichorCNA. Of the 26 patients with tissue-verified cancer-associated CNAs, 14 (54%) had corresponding CNAs in plasma. Potentially clinically actionable amplifications overlapping the genes VEGFA, EGFR and FGFR2 were detected in the plasma from three patients. CONCLUSIONS: We conclude that low-coverage whole-genome sequencing without prior knowledge of the tumour alterations could become a useful tool for cell-free tumour DNA analysis of total CNAs in plasma from patients with gastro-oesophageal cancer.

COordination of Standards in MetabOlomicS (COSMOS): facilitating integrated metabolomics data access.

Metabolomics has become a crucial phenotyping technique in a range of research fields including medicine, the life sciences, biotechnology and the environmental sciences. This necessitates the transfer of experimental information between research groups, as well as potentially to publishers and funders. After the initial efforts of the metabolomics standards initiative, minimum reporting standards were proposed which included the concepts for metabolomics databases. Built by the community, standards and infrastructure for metabolomics are still needed to allow storage, exchange, comparison and re-utilization of metabolomics data. The Framework Programme 7 EU Initiative 'coordination of standards in metabolomics' (COSMOS) is developing a robust data infrastructure and exchange standards for metabolomics data and metadata. This is to support workflows for a broad range of metabolomics applications within the European metabolomics community and the wider metabolomics and biomedical communities' participation. Here we announce our concepts and efforts asking for re-engagement of the metabolomics community, academics and industry, journal publishers, software and hardware vendors, as well as those interested in standardisation worldwide (addressing missing metabolomics ontologies, complex-metadata capturing and XML based open source data exchange format), to join and work towards updating and implementing metabolomics standards.

Data management pipeline for plant phenotyping in a multisite project.

In plant breeding, plants have to be characterised precisely, consistently and rapidly by different people at several field sites within defined time spans. For a meaningful data evaluation and statistical analysis, standardised data storage is required. Data access must be provided on a long-term basis and be independent of organisational barriers without endangering data integrity or intellectual property rights. We discuss the associated technical challenges and demonstrate adequate solutions exemplified in a data management pipeline for a project to identify markers for drought tolerance in potato. This project involves 11 groups from academia and breeding companies, 11 sites and four analytical platforms. Our data warehouse concept combines central data storage in databases and a file server and integrates existing and specialised database solutions for particular data types with new, project-specific databases. The strict use of controlled vocabularies and the application of web-access technologies proved vital to the successful data exchange between diverse institutes and data management concepts and infrastructures. By presenting our data management system and making the software available, we aim to support related phenotyping projects.

The Ectocarpus genome and the independent evolution of multicellularity in brown algae.

Brown algae (Phaeophyceae) are complex photosynthetic organisms with a very different evolutionary history to green plants, to which they are only distantly related. These seaweeds are the dominant species in rocky coastal ecosystems and they exhibit many interesting adaptations to these, often harsh, environments. Brown algae are also one of only a small number of eukaryotic lineages that have evolved complex multicellularity (Fig. 1). We report the 214 million base pair (Mbp) genome sequence of the filamentous seaweed Ectocarpus siliculosus (Dillwyn) Lyngbye, a model organism for brown algae, closely related to the kelps (Fig. 1). Genome features such as the presence of an extended set of light-harvesting and pigment biosynthesis genes and new metabolic processes such as halide metabolism help explain the ability of this organism to cope with the highly variable tidal environment. The evolution of multicellularity in this lineage is correlated with the presence of a rich array of signal transduction genes. Of particular interest is the presence of a family of receptor kinases, as the independent evolution of related molecules has been linked with the emergence of multicellularity in both the animal and green plant lineages. The Ectocarpus genome sequence represents an important step towards developing this organism as a model species, providing the possibility to combine genomic and genetic approaches to explore these and other aspects of brown algal biology further.

TAPIR, a web server for the prediction of plant microRNA targets, including target mimics.

UNLABELLED: We present a new web server called TAPIR, designed for the prediction of plant microRNA targets. The server offers the possibility to search for plant miRNA targets using a fast and a precise algorithm. The precise option is much slower but guarantees to find less perfectly paired miRNA-target duplexes. Furthermore, the precise option allows the prediction of target mimics, which are characterized by a miRNA-target duplex having a large loop, making them undetectable by traditional tools. AVAILABILITY: The TAPIR web server can be accessed at: http://bioinformatics.psb.ugent.be/webtools/tapir. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PLAZA: a comparative genomics resource to study gene and genome evolution in plants.

The number of sequenced genomes of representatives within the green lineage is rapidly increasing. Consequently, comparative sequence analysis has significantly altered our view on the complexity of genome organization, gene function, and regulatory pathways. To explore all this genome information, a centralized infrastructure is required where all data generated by different sequencing initiatives is integrated and combined with advanced methods for data mining. Here, we describe PLAZA, an online platform for plant comparative genomics (http://bioinformatics.psb.ugent.be/plaza/). This resource integrates structural and functional annotation of published plant genomes together with a large set of interactive tools to study gene function and gene and genome evolution. Precomputed data sets cover homologous gene families, multiple sequence alignments, phylogenetic trees, intraspecies whole-genome dot plots, and genomic colinearity between species. Through the integration of high confidence Gene Ontology annotations and tree-based orthology between related species, thousands of genes lacking any functional description are functionally annotated. Advanced query systems, as well as multiple interactive visualization tools, are available through a user-friendly and intuitive Web interface. In addition, detailed documentation and tutorials introduce the different tools, while the workbench provides an efficient means to analyze user-defined gene sets through PLAZA's interface. In conclusion, PLAZA provides a comprehensible and up-to-date research environment to aid researchers in the exploration of genome information within the green plant lineage.