Alternative splicing and transcriptome profiling of experimental autoimmune encephalomyelitis using genome-wide exon arrays

BACKGROUND: Multiple Sclerosis (MS) is a chronic inflammatory disease causing demyelination and nerve loss in the central nervous system. Experimental autoimmune encephalomyelitis (EAE) is an animal model of MS that is widely used to investigate complex pathogenic mechanisms. Transcriptional control through isoform selection and mRNA levels determines pathway activation and ultimately susceptibility to disease. METHODOLOGY/PRINCIPAL FINDINGS: We have studied the role of alternative splicing and differential expression in lymph node cells from EAE-susceptible Dark Agouti (DA) and EAE-resistant Piebald Virol Glaxo.AV1 (PVG) inbred rat strains using Affymetrix Gene Chip Rat Exon 1.0 ST Arrays. Comparing the two strains, we identified 11 differentially spliced and 206 differentially expressed genes at day 7 post-immunization, as well as 9 differentially spliced and 144 differentially expressed genes upon autoantigen re-stimulation. Functional clustering and pathway analysis implicate genes for glycosylation, lymphocyte activation, potassium channel activity and cellular differentiation in EAE susceptibility. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that alternative splicing occurs during complex disease and may govern EAE susceptibility. Additionally, transcriptome analysis not only identified previously defined EAE pathways regulating the immune system, but also novel mechanisms. Furthermore, several identified genes overlap known quantitative trait loci, providing novel causative candidate targets governing EAE

Visual Supercomputing – technologies, applications and challenges. Eurographics STAR- 2, State of the Art report. European Association for Computer Graphics: Switzerland. N.B. Revised version to be published in Computer Graphics Forum Issue 24 Number 2, 2

If we were to have a Grid infrastructure for visualization, what technologies would be needed to build such an infrastructure, what kind of applications would benefit from it, and what challenges are we facing in order to accomplish this goal? In this survey paper, we make use of the term ‘visual supercomputing ’ to encapsulate a subject domain concerning the infrastructural technology for visualization. We consider a broad range of scientific and technological advances in computer graphics and visualization, which are relevant to visual supercomputing. We identify the state-of-the-art technologies that have prepared us for building such an infrastructure. We examine a collection of applications that would benefit enormously from such an infrastructure, and discuss their technical requirements. We propose a set of challenges that may guide our strategic efforts in the coming years