The Erasmus Computing Grid – Building a Super-Computer for Free

Today advances in scientific research as well as clinical diagnostics and treatment are inevitably connected with information solutions concerning computation power and information storage. The needs for information technology are enormous and are in many cases the limiting factor for new scientific results or clinical diagnostics and treatment. At the Hogeschool Rotterdam and the Erasmus MC there is a massive need for computation power on a scale of 10,000 to 15,000 computers equivalent to ~20 to ~30 Tflops (1012 floating point operations per second) for a variety of work areas ranging from e.g. MRI and CT scan and microscopic image anlysis to DNA sequence analysis, protein and other structural simulations and analysis. Both institutions have already 13,000 computers, i.e. ~18 Tflops of computer power, available! To make the needed computer power accessible, we started to build the Erasmus Computing Grid (ECG), which is connecting local computers in each institution via central management systems. The system guaranties security and any privacy rules through the used software as well as through our set-up and a NAN and ISO certification process being under way. Similar systems run already world-wide on entire institutions including secured environments like government institutions or banks. Currently, the ECG has a computational power of ~5 Tflops and is one of or already the largest desktop grid in the world. At the Hogeschool Rotterdam meanwhile all computers were included in the ECG. Currently, 10 departments with ~15 projects at the Erasmus MC depend on using the ECG and are preparing or prepared their analysis programs or are already in production state. The Erasmus Computing Grid office and an advisory and control board were set-up. To sustain the ECG now further infrastructure measures have to be taken. Central hardware and specialist personal needs to be put in place for capacity, security and usability reasons for the application at Erasmus MC. This is also necessary in respect to NAN and ISO certification towards diagnostic and commercial ECG use, for which there is great need and potential. Beyond the link to the Dutch BigGrid Initiative and the German MediGRID should be prepared for and realized due to the great interest for cooperation. There is also big political interest from the government to relieve the pressure on computational needs in The Netherlands and to strengthen the Dutch position in the field of high performance computing. In both fields the ECG should be brought into a leading position by establishing the Erasmus MC a centre of excellence for high-performance computing in the medical field in respect to Europe and world-wide. Consequently, we successfully started to build a super-computer at the Hogeschool Rotterdam and Erasmus MC with great opportunities for scientific research, clinical diagnostics and research as well as student training. This will put both institutions in the position to play a major world-wide role in high-performance computing. This will open entire new possibilities for both institutions in terms of recognition and new funding possibilities and is of major importance for The Netherlands and the EU

DNA Sequence Patterns – A Successful Example of Grid Computing in Genome Research and Building Virtual Super-Computers for the Research Commons of e-Societies

The amount of information is growing exponentially with ever-new technologies emerging and is believed to be always at the limit. In contrast, huge resources are obviously available, which are underused in the IT sector, similar as e.g. in the renewable energy sector. Genome research is one of the boosting areas, which needs an extreme amount of IT resources to analyse the sequential organization of genomes, i.e. the relations between distant base pairs and regions within sequences, and its connection to the three-dimensional organization of genomes, which is still a largely unresolved problem. The underusage of resources as those accessible by grid with its fast turnover rates is very astonishing considering the barriers for further development put forward by the inability to satisfy the need for such resources. The phenomenon is a typical example of the Inverse Tragedy of the Commons, i.e. resources are underexploited in contrast to the unsustainable and destructing overexploitation in the Classic Tragedy of the Commons. An analysis of IT and the grid sector which attempts to share resources for better usage efficiency, reveals two challenges, which lead to the heart of the paradox: i) From a macro perspective all grid infrastructures involve not only mere technical solutions but also dominantly all of the autopoietic social sub-systems ranging from religion to policy. ii) On the micro level the individual players and their psychology and risk behaviour are of major importance for acting within the macro autopoietic framework. Consequently, the challenges of grid implementation are similar to those of other pressing global issues as e.g. climate protection. This is well described by extending the Human Ecology triangle to a rectangle: invironment-individual-society-environment. By applying this extension of this classical field of interdisciplinary basic and applied research to the grid sector, i.e. by further extension to an e-Human Grid Ecology rational, the Grid Inverse Tragedy of the Commons can be understood and approached regarding the internalization challenge into e-Society and e-Life, from which then guidelines for the day-to-day management can be derived. This is of general importance for many complex fields and thus with similar paradoxes and challenges. By using grid Long-range power-law correlations were found using correlation analysis on almost the entire observable scale of 132 completely sequenced chromosomes of 0.5x106 to 3.0x107 bp from Archaea, Bacteria, Arabidopsis thaliana, Saccharomyces cerevisiae, Schizosaccharomyces pombe, Drosophila melanogaster and Homo sapiens. The local correlation coeffi

GRIMP: A web- and grid-based tool for high-speed analysis of large-scale genome-wide association using imputed data.

The current fast growth of genome-wide association studies (GWAS) combined with now common computationally expensive imputation requires the online access of large user groups to high-performance computing resources capable of analyzing rapidly and efficiently millions of genetic markers for ten thousands of individuals. Here, we present a web-based interface—called GRIMP—to run publicly available genetic software for extremely large GWAS on scalable super-computing grid infrastructures. This is of major importance for the enlargement of GWAS with the availability of whole-genome sequence data from the 1000 Genomes Project and for future whole-population efforts

The detailed 3D multi-loop aggregate/rosette chromatin architecture and functional dynamic organization of the human and mouse genomes

Background: The dynamic three-dimensional chromatin architecture of genomes and its co-evolutionary connection to its function—the storage, expression, and replication of genetic information—is still one of the central issues in biology. Here, we describe the much debated 3D architecture of the human and mouse genomes from the nucleosomal to the megabase pair level by a novel approach combining selective high-throughput high-resolution chromosomal interaction capture (T2C), polymer simulations, and scaling analysis of the 3D architecture and the DNA sequence. Results: The genome is compacted into a chromatin quasi-fibre with ~5 ± 1 nucleosomes/11 nm, folded into stable ~30–100 kbp loops forming stable loop aggregates/rosettes connected by similar sized linkers. Minor but significant variations in the architecture are seen between cell types and functional states. The architecture and the DNA sequence show very similar fine-structured multi-scaling behaviour confirming their co-evolution and the above. Conclusions: This architecture, its dynamics, and accessibility, balance stability and flexibility ensuring genome integrity and variation enabling gene expression/regulation by self-organization of (in)active units already in proximity. Our results agree with the heuristics of the field and allow “architectural sequencing” at a genome mechanics level to understand the inseparable systems genomic properties

Fine-structured multi-scaling long-range correlations in completely sequenced genomes—features, origin, and classification

The sequential organization of genomes, i.e. the relations between distant base pairs and regions within sequences, and its connection to the three-dimensional organization of genomes is still a largely unresolved problem. Long-range power-law correlations were found using correlation analysis on almost the entire observable scale of 132 completely sequenced chromosomes of 0.5 × 106 to 3.0 × 107 bp from Archaea, Bacteria, Arabidopsis thaliana, Saccharomyces cerevisiae, Schizosaccharomyces pombe, Drosophila melanogaster, and Homo sapiens. The local correlation coefficients show a species-specific multi-scaling behaviour: close to random correlations on the scale of a few base pairs, a first maximum from 40 to 3,400 bp (for Arabidopsis thaliana and Drosophila melanogaster divided in two submaxima), and often a region of one or more second maxima from 105 to 3 × 105 bp. Within this multi-scaling behaviour, an additional fine-structure is present and attributable to codon usage in all except the human sequences, where it is related to nucleosomal binding. Computer-generated random sequences assuming a block organization of genomes, the codon usage, and nucleosomal binding explain these results. Mutation by sequence reshuffling destroyed all correlations. Thus, the stability of correlations seems to be evolutionarily tightly controlled and connected to the spatial genome organization, especially on large scales. In summary, genomes show a complex sequential organization related closely to their three-dimensional organization

The Detailed 3D Multi-Loop Aggregate/Rosette Chromatin Architecture and Functional Dynamic Organization of the Human and Mouse Genomes. - BioRxiv Version

The dynamic three-dimensional chromatin architecture of genomes and its coevolutionary connection to its function – the storage, expression, and replication of genetic information – is still one of the central issues in biology. Here, we describe the much debated 3D-architecture of the human and mouse genomes from the nucleosomal to the megabase pair level by a novel approach combining selective high-throughput high-resolution chromosomal interaction capture (T2C), polymer simulations, and scaling analysis of the 3D-architecture and the DNA sequence: The genome is compacted into a chromatin quasi-fibre with ~5±1 nucleosomes/11nm, folded into stable ~30-100 kbp loops forming stable loop aggregates/

The detailed 3D multi-loop aggregate/rosette chromatin architecture and functional dynamic organization of the human and mouse genomes. - Epigenetics & Chromatin Version

Background: The dynamic three-dimensional chromatin architecture of genomes and its co-evolutionary connection to its function - the storage, expression, and replication of genetic information - is still one of the central issues in biology. Here, we describe the much debated 3D architecture of the human and mouse genomes from the nucleosomal to the megabase pair level by a novel approach combining selective high-throughput high-resolution chromoso