Application of regulatory sequence analysis and metabolic network analysis to the interpretation of gene expression data

We present two complementary approaches for the interpretation of clusters of co-regulated genes, such as those obtained from DNA chips and related methods. Starting from a cluster of genes with similar expression profiles, two basic questions can be asked: 1. Which mechanism is responsible for the coordinated transcriptional response of the genes? This question is approached by extracting motifs that are shared between the upstream sequences of these genes. The motifs extracted are putative cis-acting regulatory elements. 2. What is the physiological meaning for the cell to express together these genes? One way to answer the question is to search for potential metabolic pathways that could be catalyzed by the products of the genes. This can be done by selecting the genes from the cluster that code for enzymes, and trying to assemble the catalyzed reactions to form metabolic pathways. We present tools to answer these two questions, and we illustrate their use with selected examples in the yeast Saccharomyces cerevisiae. The tools are available on the web (http://ucmb.ulb.ac.be/bioinformatics/rsa-tools/; http://www.ebi.ac.uk/research/pfbp/; http://www.soi.city.ac.uk/~msch/)

RSAT 2011: regulatory sequence analysis tools

RSAT (Regulatory Sequence Analysis Tools) comprises a wide collection of modular tools for the detection of cis-regulatory elements in genome sequences. Thirteen new programs have been added to the 30 described in the 2008 NAR Web Software Issue, including an automated sequence retrieval from EnsEMBL (retrieve-ensembl-seq), two novel motif discovery algorithms (oligo-diff and info-gibbs), a 100-times faster version of matrix-scan enabling the scanning of genome-scale sequence sets, and a series of facilities for random model generation and statistical evaluation (random-genome-fragments, random-motifs, random-sites, implant-sites, sequence-probability, permute-matrix). Our most recent work also focused on motif comparison (compare-matrices) and evaluation of motif quality (matrix-quality) by combining theoretical and empirical measures to assess the predictive capability of position-specific scoring matrices. To process large collections of peak sequences obtained from ChIP-seq or related technologies, RSAT provides a new program (peak-motifs) that combines several efficient motif discovery algorithms to predict transcription factor binding motifs, match them against motif databases and predict their binding sites. Availability (web site, stand-alone programs and SOAP/WSDL (Simple Object Access Protocol/Web Services Description Language) web services): http://rsat.ulb.ac.be/rsat/

RSAT: regulatory sequence analysis tools

The regulatory sequence analysis tools (RSAT, http://rsat.ulb.ac.be/rsat/) is a software suite that integrates a wide collection of modular tools for the detection of cis-regulatory elements in genome sequences. The suite includes programs for sequence retrieval, pattern discovery, phylogenetic footprint detection, pattern matching, genome scanning and feature map drawing. Random controls can be performed with random gene selections or by generating random sequences according to a variety of background models (Bernoulli, Markov). Beyond the original word-based pattern-discovery tools (oligo-analysis and dyad-analysis), we recently added a battery of tools for matrix-based detection of cis-acting elements, with some original features (adaptive background models, Markov-chain estimation of P-values) that do not exist in other matrix-based scanning tools. The web server offers an intuitive interface, where each program can be accessed either separately or connected to the other tools. In addition, the tools are now available as web services, enabling their integration in programmatic workflows. Genomes are regularly updated from various genome repositories (NCBI and EnsEMBL) and 682 organisms are currently supported. Since 1998, the tools have been used by several hundreds of researchers from all over the world. Several predictions made with RSAT were validated experimentally and published

The resistance of lettuce to the aphid Nasonovia ribisnigri

The resistance of lettuce to the aphid Nasonovia ribisnigri is based on a single, dominant gene, the Nr-gene. On the resistant plant aphids died within a few days, without any honeydew production. Transfer-experiments with a short stay on a resistant plant followed by a relocation to a susceptible plant showed that no weight increase occurred on the resistant plant, but weight gain immediately resumed on a susceptible plant (Chapter 2). So no intoxication seemed to occur on the resistant plant. Behavioral observations of (tethered) aphids using Electrical Penetration Graphs (EPG) (Chapter 3) and comparison with free living aphids (Chapter 4) showed that on the resistant plant the aphid's stylets did penetrate to the phloem sieve elements. On the resistant plants hardly any E2 pattern (phloem sap ingestion) occurred and the aphid finally died of malnutrition, or left the plant (Chapter 4). It was concluded that the resistance is based on a factor in the phloem. This can be either a chemical factor like a feeding deterrent or a mechanical factor which obstructs ingestion. Experiments concentrated on chemical differences in the phloem sap of resistant and susceptible (isogenic apart from the resistance gene) lettuce lines. Amputation of aphid stylets (stylectomy) during feeding can yield small but pure phloem sap samples. However, on the resistant and susceptible isogenic lines no phloem sap samples could be collected because outflow from the stylet stump stopped after a few seconds. Larger phloem sap samples were obtained by EDTA chelation and honeydew collection (Chapter 5).Chemical analysis of the composition of the phloem sap samples showed no differences in sugars, amino acids, proteins and UV absorbing compounds (Chapter 6). Exhaustive analysis of phloem sap compounds was not feasible, not only because of the number of possible compounds, but also because the sample size and quantity was limited.In a bioassay aphids were offered a choice between EDTA collected phloem sap samples of resistant and susceptible plants, added to a complete artificial diet (chapter 7). Aphids showed a clear aversion to the extract of the resistant plant. This suggests that the resistance is based on the presence of feeding deterrents in the phloem sap of the resistant plant. Hopefully, these substances can be isolated and identified with the help of the bioassay

ReSolVe : restaurer la fertilité des sols viticoles en agriculture biologique

Le projet ReSolVe (programme Core Organic Plus) regroupe 6 pays dans l’objectif de restaurer la fertilité des sols viticoles par des méthodes alternatives dans des parcelles conduites en agriculture biologique présentant des zones caractérisées par des déficiences de vigueur, de récolte ou encore de qualité. L’objectif est de tester des techniques compatibles avec l’agriculture biologique afin de rétablir la fertilité et le fonctionnement du sol dans ces zones dégradées : ajout de compost, semis d’engrais verts, et semis d’un enherbement géré en mulch. 6 parcelles d'essai ont été mises en place en France. Les relations entre caractéristiques des sols, biodiversité (dont mésofaune), décomposition de la matière organique et conséquences sur la productivité de la vigne ont été évaluées lors d'une première année témoin en 2015 et les effets de la mise en place des modalités commencent à être évalués en 2016

The First Three Rungs of the Cosmological Distance Ladder

It is straightforward to determine the size of the Earth and the distance to the Moon without making use of a telescope. The methods have been known since the 3rd century BC. However, few amateur or professional astronomers have worked this out from data they themselves have taken. Here we use a gnomon to determine the latitude and longitude of South Bend, Indiana, and College Station, Texas, and determine a value of the radius of the Earth of 6290 km, only 1.4 percent smaller than the true value. We use the method of Aristarchus and the size of the Earth's shadow during the lunar eclipse of 2011 June 15 to derive an estimate of the distance to the Moon (62.3 R_Earth), some 3.3 percent greater than the true mean value. We use measurements of the angular motion of the Moon against the background stars over the course of two nights, using a simple cross staff device, to estimate the Moon's distance at perigee and apogee. Finally, we use simultaneous CCD observations of asteroid 1996 HW1 obtained with small telescopes in Socorro, New Mexico, and Ojai, California, to derive a value of the Astronomical Unit of (1.59 +/- 0.19) X 10^8 km, about 6 percent too large. The data and methods presented here can easily become part of a beginning astronomy lab class.Comment: 34 pages, 11 figures, accepted for publication in American Journal of Physic

Automated Method for the Determination of 5′-Nucleotidase in Serum by Continuous Flow Analysis

Peer Reviewe