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Data-intensive research depends on tools that manage multi-dimensional, heterogeneous data sets. We have built OME Remote Objects (OMERO), a software platform that enables access to and use of a wide range of biological data. OMERO uses a server-based middleware application to provide a unified interface for images, matrices, and tables. OMERO’s design and flexibility have enabled its use for light microscopy, high content screening, electron microscopy, and even non-image genotype data. OMERO is open source software and available at http://openmicroscopy.org.

A training system for simulating temporal bone surgery is presented. The system is based on patient-specific volumetric object models derived from 3D CT and MR imaging data. Real-time feedback is provided to the trainees via real-time volume rendering and haptic feedback. The performance constraints dictated by the human perceptual system are met by exploiting parallelism via a decoupled simulation approach on a multi-processor PC platform. In this paper, system components are detailed and the current state of the integrated system is presented.

With vast increases in biological data generation, mechanisms for data storage and analysis have become limiting. A data structure, semantically typed data hypercubes (SDCubes), that combines hierarchical data format version 5 (HDF5) and extensible markup language (XML) file formats, now permits the flexible storage, annotation and retrieval of large and heterogenous datasets.

The analysis of the genomic distribution of viral vector genomic integration sites is a key step in hematopoietic stem cell-based gene therapy applications, allowing to assess both the safety and the efficacy of the treatment and to study the basic aspects of hematopoiesis and stem cell biology. Identifying vector integration sites requires ad-hoc bioinformatics tools with stringent requirements in terms of computational efficiency, flexibility, and usability. We developed VISPA (Vector Integration Site Parallel Analysis), a pipeline for automated integration site identification and annotation based on a distributed environment with a simple Galaxy web interface. VISPA was successfully used for the bioinformatics analysis of the follow-up of two lentiviral vector-based hematopoietic stem-cell gene therapy clinical trials. Our pipeline provides a reliable and efficient tool to assess the safety and efficacy of integrating vectors in clinical settings. Electronic supplementary material The online version of this article (doi:10.1186/s13073-014-0067-5) contains supplementary material, which is available to authorized users.

Oncogenesis induced by insertional mutagenesis with gene therapy vectors occurs mainly by activation of proto-oncogenes found at or nearby the insertion site. This activation often occurs by an enhancer-mediated mechanism or by a process of splicing capture which generates chimeric transcripts comprising portions of vector and cellular mRNAs. Although the activation of oncogenes may be reduced by the use of self-inactivating design and moderate cellular promoters, how to reduce genotoxic splicing capture events and aberrant transcript formation triggered by vector integration is still unclear. We developed a modified Linear Amplification-Mediated (LAM) PCR technique, named cDNA LAM PCR (cLAM-PCR), aimed at retrieving, from the whole transcriptome of LV-transduced cells aberrantly spliced mRNAs that contain lentiviral vector (LV) sequences fused with cellular transcripts in a high-throughput fashion. The sequences of cLAM-PCR products were obtained by 454 pyrosequencing and analyzed by dedicated high-throughput computational pipeline running in a computer cluster that use a dynamic analysis process composed by different steps based on a map-reduce parallelization model. Thus, chimeric LV-genome sequences are recognized, the nucleotide position of the fused sequence is identified (the splice site), and the remaining portion mapped on the appropriate genome assembly by BLAST. We identified several established and previously unknown splice sites within the LV backbone that participate in the aberrant splicing process with variable efficiency. Results obtained with different LV designs show that integrated LVs can perturb the processing of cellular transcripts by interacting with the cellular splicing machinery and fusing with its own splice sites to cellular splice sites both upstream and downstream the integration site. So far, 70 different fusion transcripts could be identified in total, 84% of which were fused to known splice sites of gene exons, 6% were fused to uncharacterized cryptic splice sites located in introns and the remaining 10% were fused to genomic sequences not corresponding to any annotated gene. This analysis allows identifying also several different slice sites within the LV backbone that participated to the aberrabt splicing process. Quantitative PCR on different LV portions within the LV backbone allow measuring the relative contribution to the aberrant splicing process of each splice site identified. Interestingly, the amount of transcription occurring in regions outside the expression cassette reaches the 3% of the entire transgene expression. The cLAM-PCR technique, coupled to high-throughput sequencing and the computational power of our specialized data analysis pipeline allows gaining insights into the biology of vector-mediated splicing alteration. Since this process could induce neoplastic transformation by the generation of aberrant oncogenic protein, its in-depth characterization is instrumental in the development of next-generation LV with a higher safety profile.

Results of a numerical study of the dynamics of a collection of disks colliding inelastically in a periodic two-dimensional enclosure are presented. The properties of this system, which is perhaps the simplest model for rapidly flowing granular materials, are markedly different from those known for atomic or moleclar gases, in which collisions are of elastic nature. The most prominent feature characterizing granular systems, even in the idealized situation in which no external forcing exists and the initial condition is statistically homogeneous, is their inherent instability to inhomogeneous fluctuations. Granular “gases” are thus generically nonuniform, a fact that suggests extreme caution in pursuing direct analogies with molecular gases. We find that once an inhomogeneous state sets in, the velocity distribution functions differ from the classical Maxwell-Boltzmann distribution. Other characteristics of the system are different from their counterparts in molecular systems as well. For a given value of the coefficient of restitution,e, a granular system forms clusters of typical separationL0≈l/(1-e2)1/2, wherel is the mean free path in the corresponding homogeneous system. Most of the fluctuating kinetic energy then resides in the relatively dilute regions that surround the clusters. Systems whose linear dimensions are less thenL0 do not give rise to clusters; still they are inhomogeneous, the scale of the corresponding inhomogeneity being the longest wavelength allowed by the system's size. The present article is devoted to a detailed numerical study of the above-mentioned clustering phenomenon in two dimensions and in the absence of external forcing. A theoretical framework explaining this phenomenon is outlined. Some general implications as well as practical ramifications are discussed.

As a model problem for the perturbation, up to break up, of tori in Hamiltonian mechanics, the map of the circle into itself is studied.