Spyder:a reconfigurable processor development system

The Spyder project consists of the development of a reconfigurable processor as well as its application development environment. The name Spyder is an anagram of the first letters of "REconfigurable Processor Development SYstem", where the term reconfigurable means that the hardware of the processor can be specifically tailored for each application. Augmenting the performance of a processor implies either increasing its clock frequency or modifying its architecture. In the latter case, the solution usually adopted is to endow the processor with multiple execution units working in parallel (superscalar processors). The main problem with this kind of processors is to locate, in the sequential list of instructions of a program, batches of instructions susceptible of being executed in parallel by the different execution units of the processor. Thanks to the advent of field-programmable gate array (FPGA) circuits, new kind of superscalar processor architectures can be considered. In particular, the Spyder processor features multiple reconfigurable execution units, which can be redesigned to fit each application, a feature which greatly increases the opportunities to perform parallel computations, particularly when working with small data elements (e.g., 16 Boolean data can be packed into a single 16-bit data word and processed in parallel by a specifically designed operation in the execution unit). All the resources of the Spyder processor operate in parallel and are controlled by a very large instruction word (VLIW) 128 bits wide. The VLIW architecture allows the use of the full parallelism available to superscalar processors without requiring the complex dispatch unit needed by such processors to handle sequential scalar instructions. The goal of the Spyder project is to design and implement a superscalar processor with multiple reconfigurable execution units, as well as the software development tools (i.e., C++ compilers and a VLIW assembler) necessary to generate applications for this processor. A prototype of the Spyder processor has been implemented on a VME board, which has been installed in a VME rack along with a SPARC board acting as host computer. A C++ compiler generating netlist files for the ViewLogic CAD tools has been developed and has generated a lot of interest in the scientific community. It is now available by anonymous ftp on the Internet. Image processing applications and cellular automata simulations have been programmed on the Spyder processor. The Spyder prototype has demonstrated its ability to achieve a high level of performance with these applications

The Aesthetics and Perception of Documentary Film: A mixed methods approach and Its implications for Artistic Research

The ongoing research project Gadgets, Phones and Drones at the Zurich University of the Arts investigates how innovations in camera technology have affected the visual aesthetics of documentary films since the 1990s. With specially produced variants of short films, historical paradigm shifts are being subjected to contemporary comparative analyses. Major aspects of the aesthetic change, as for instance the tendency towards a shallow depth of field, are linked to the concept of authenticity or perceived realism. The project’s use of interdisciplinary research is oriented towards artistic research, or more precisely, towards a practice-based approach and is combined with empirical audience experiments. The dialogue between qualitative and quantitative research, also known as mixed methods, has enabled surprising new insights. However, the comparability of quantitative methods risks narrowing down the aesthetic potential of the filmic products that are used to conduct the research. In order to maintain a discriminating discourse within the practice-based approach, it is therefore advantageous to extend the study’s framework beyond a quantitative and comparative research set-up and provide specific fields for artistic investigations

Neighbor predation linked to natural competence fosters the transfer of large genomic regions in Vibrio cholerae

Natural competence for transformation is a primary mode of horizontal gene transfer. Competent bacteria are able to absorb free DNA from their surroundings and exchange this DNA against pieces of their own genome when sufficiently homologous. However, the prevalence of non-degraded DNA with sufficient coding capacity is not well understood. In this context, we previously showed that naturally competent Vibrio cholerae use their type VI secretion system (T6SS) to actively acquire DNA from non-kin neighbors. Here, we explored the conditions of the DNA released through T6SS-mediated killing versus passive cell lysis and the extent of the transfers that occur due to these conditions. We show that competent V. cholerae acquire DNA fragments with a length exceeding 150 kbp in a T6SS-dependent manner. Collectively, our data support the notion that the environmental lifestyle of V. cholerae fosters the exchange of genetic material with sufficient coding capacity to significantly accelerate bacterial evolution

Probabilistic base calling of Solexa sequencing data

BACKGROUND: Solexa/Illumina short-read ultra-high throughput DNA sequencing technology produces millions of short tags (up to 36 bases) by parallel sequencing-by-synthesis of DNA colonies. The processing and statistical analysis of such high-throughput data poses new challenges; currently a fair proportion of the tags are routinely discarded due to an inability to match them to a reference sequence, thereby reducing the effective throughput of the technology. RESULTS: We propose a novel base calling algorithm using model-based clustering and probability theory to identify ambiguous bases and code them with IUPAC symbols. We also select optimal sub-tags using a score based on information content to remove uncertain bases towards the ends of the reads. CONCLUSION: We show that the method improves genome coverage and number of usable tags as compared with Solexa's data processing pipeline by an average of 15%. An R package is provided which allows fast and accurate base calling of Solexa's fluorescence intensity files and the production of informative diagnostic plots

Ultra high throughput sequencing excludes MDH1 as candidate gene for RP28-linked retinitis pigmentosa

PURPOSE: Mutations in IDH3B, an enzyme participating in the Krebs cycle, have recently been found to cause autosomal recessive retinitis pigmentosa (arRP). The MDH1 gene maps within the RP28 arRP linkage interval and encodes cytoplasmic malate dehydrogenase, an enzyme functionally related to IDH3B. As a proof of concept for candidate gene screening to be routinely performed by ultra high throughput sequencing (UHTs), we analyzed MDH1 in a patient from each of the two families described so far to show linkage between arRP and RP28. METHODS: With genomic long-range PCR, we amplified all introns and exons of the MDH1 gene (23.4 kb). PCR products were then sequenced by short-read UHTs with no further processing. Computer-based mapping of the reads and mutation detection were performed by three independent software packages. RESULTS: Despite the intrinsic complexity of human genome sequences, reads were easily mapped and analyzed, and all algorithms used provided the same results. The two patients were homozygous for all DNA variants identified in the region, which confirms previous linkage and homozygosity mapping results, but had different haplotypes, indicating genetic or allelic heterogeneity. None of the DNA changes detected could be associated with the disease. CONCLUSIONS: The MDH1 gene is not the cause of RP28-linked arRP. Our experimental strategy shows that long-range genomic PCR followed by UHTs provides an excellent system to perform a thorough screening of candidate genes for hereditary retinal degeneration

Cell-free DNA testing of an extended range of chromosomal anomalies: clinical experience with 6,388 consecutive cases

PURPOSE: Cell-free DNA (cfDNA) testing for fetal aneuploidies was broadly implemented for common trisomies and sex-chromosome anomalies (SCAs). However, such an approach identifies only 75 to 85% of clinically relevant aneuploidies. METHODS: We present a consecutive series of 6,388 cases, thus uncovering a broader array of aneuploidies, including the rare autosomal trisomies (RATs) and the maternally inherited deletion and duplication copy-number variations (CNVs), with complete and stratified follow-up by amniocentesis. Combined measurements of z-scores and the fetal fraction, in conjunction with fetal cfDNA enrichment, were used to stratify the likelihood of true and false results. RESULTS: We obtained an incremental diagnostic yield of 50%; RATs and CNVs were found to be significant causes of fetal pathology. Scrutinizing z-scores and the fetal fraction made it possible to distinguish the sources of false-negative results; predict the likelihood of false-positive results for major trisomies and SCAs; classify maternal mosaic SCAs and CNVs, preventing false-positive results; and robustly identify maternally inherited CNVs and detect recurrent genomic disorders as a standardized function of the fetal fraction. CONCLUSION: With the clinical pertinence of this broader detection scheme confirmed, we offer recommendations for its implementation. Genet Med 19 2, 169–175

Inhibition of anti-tumor immunity by melanoma cell-derived Activin-A depends on STING

The transforming growth factor-β (TGF-β) family member activin A (hereafter Activin-A) is overexpressed in many cancer types, often correlating with cancer-associated cachexia and poor prognosis. Activin-A secretion by melanoma cells indirectly impedes CD8+ T cell-mediated anti-tumor immunity and promotes resistance to immunotherapies, even though Activin-A can be proinflammatory in other contexts. To identify underlying mechanisms, we here analyzed the effect of Activin-A on syngeneic grafts of Braf mutant YUMM3.3 mouse melanoma cells and on their microenvironment using single-cell RNA sequencing. We found that the Activin-A-induced immune evasion was accompanied by a proinflammatory interferon signature across multiple cell types, and that the associated increase in tumor growth depended at least in part on pernicious STING activity within the melanoma cells. Besides corroborating a role for proinflammatory signals in facilitating immune evasion, our results suggest that STING holds considerable potential as a therapeutic target to mitigate tumor-promoting Activin-A signaling at least in melanoma

Detection of Genomic Variation by Selection of a 9 Mb DNA Region and High Throughput Sequencing

Detection of the rare polymorphisms and causative mutations of genetic diseases in a targeted genomic area has become a major goal in order to understand genomic and phenotypic variability. We have interrogated repeat-masked regions of 8.9 Mb on human chromosomes 21 (7.8 Mb) and 7 (1.1 Mb) from an individual from the International HapMap Project (NA12872). We have optimized a method of genomic selection for high throughput sequencing. Microarray-based selection and sequencing resulted in 260-fold enrichment, with 41% of reads mapping to the target region. 83% of SNPs in the targeted region had at least 4-fold sequence coverage and 54% at least 15-fold. When assaying HapMap SNPs in NA12872, our sequence genotypes are 91.3% concordant in regions with coverage≥4-fold, and 97.9% concordant in regions with coverage≥15-fold. About 81% of the SNPs recovered with both thresholds are listed in dbSNP. We observed that regions with low sequence coverage occur in close proximity to low-complexity DNA. Validation experiments using Sanger sequencing were performed for 46 SNPs with 15-20 fold coverage, with a confirmation rate of 96%, suggesting that DNA selection provides an accurate and cost-effective method for identifying rare genomic variants

Fourmidable: a database for ant genomics

BACKGROUND: Fourmidable is an infrastructure to curate and share the emerging genetic, molecular, and functional genomic data and protocols for ants. DESCRIPTION: The Fourmidable assembly pipeline groups nucleotide sequences into clusters before independently assembling each cluster. Subsequently, assembled sequences are annotated via Interproscan and BLAST against general and insect-specific databases. Gene-specific information can be retrieved using gene identifiers, searching for similar sequences or browsing through inferred Gene Ontology annotations. The database will readily scale as ultra-high throughput sequence data and sequences from additional species become available. CONCLUSION: Fourmidable currently houses EST data from two ant species and microarray gene expression data for one of these. Fourmidable is publicly available at http://fourmidable.unil.ch