Vicente Arnau

Iterative Cluster Analysis of Protein Interaction Data

MOTIVATION Generation of fast tools of hierarchical clustering to be applied when distances among elements of a set are constrained, causing frequent distance ties, as happens in protein interaction data. RESULTS We present in this work the program UVCLUSTER, that iteratively explores distance datasets using hierarchical clustering. Once the user selects a group of proteins, UVCLUSTER converts the set of primary distances among them (i.e. the minimum number of steps, or interactions, required to connect two proteins) into secondary distances that measure the strength of the connection between each pair of proteins when the interactions for all the proteins in the group are considered. We show that this novel strategy has advantages over conventional clustering methods to explore protein-protein interaction data. UVCLUSTER easily incorporates the information of the largest available interaction datasets to generate comprehensive primary distance tables. The versatility, simplicity of use and high speed of UVCLUSTER on standard personal computers suggest that it can be a benchmark analytical tool for interactome data analysis. AVAILABILITY The program is available upon request from the authors, free for academic users. Additional information available at http://www.uv.es/genomica/UVCLUSTER.

Direct Objective Quantification of Corneal Haze after Excimer Laser Photorefractive Keratectomy for High Myopia

PURPOSE The purpose of the study is to measure regional distribution differences in corneal haze after excimer laser photorefractive keratectomy for high myopia. METHODS The authors developed computerized gradient edge detectors with which were analyzed digitized anterior slit-lamp photographs of 40 eyes, an average of 21.0 plus or minus 14.5 weeks after photorefractive keratectomy for high myopia (-6 to -22 diopters). A treated area an adjacent untreated area on the anterior corneal surface, each containing six regions, were quantified, and the difference was correlated with various parameters. RESULTS Mean differences between scarred and clear areas for haze grade 0.5, 1.0, 2.0, 3.0, and 4.0 were 16.9, 26.6, 42.6, 60.4, and 76.4 gray levels, respectively (rs = 0.96; P = 0.0001). A low but statistically significant correlation between the intended correction and postoperative corneal haze was found (r = 0.33; P = 0.037). The mean coefficient of variation of the amount of opacification within each treated area was 9.4%. This coefficient of variation increased with a longer follow-up time (r = 0.88; P = 0.0001). The difference in the intensity of haze between the center and more peripheral regions over the entrance pupil did not correlate with the attempted correction. However, a strong association between a relatively less severe central corneal haze with respect to more peripheral haze and longer follow-up time was found (r = -0.96; P = 0.0001). CONCLUSION The amount of corneal haze showed a weak positive association with the attempted correction in excimer laser photorefractive keratectomy for high myopia. Corneal haze appeared fairly uniformly distributed within the ablation zone, but a more heterogeneous distribution was found with a longer follow-up time. Furthermore, later postoperative examinations disclosed a clear trend toward diminishing central opacification relative to peripheral regions over the entrance pupil.

Reproducibility of Digital Image Analysis for Measuring Corneal Haze After Myopic Photorefractive Keratectomy

PURPOSE To evaluate the usefulness of digital image analysis for quantifying corneal haze by determining the reproducibility of its measurements at the corneal plane. METHODS In a prospective study, 20 randomly selected eyes that had undergone myopic photorefractive keratectomy were photographed focusing the slit beam on their anterior corneal surface. Each photograph was examined using computer image analysis techniques that detect the edge of the reticular pattern of the image. Quantification of the difference between two areas, treated and adjacent untreated cornea, each containing 3,750 pixels with a resolution of 256 gray levels, was performed. Intra-analyzer variation was determined by evaluating the photographs obtained by two analyzers under standard conditions on four separate visits. Interanalyzer variation was calculated using one measurement and the mean of the four measurements. RESULTS The pooled standard deviation of the measurements for the analyzers was 0.63 and 0.62 gray levels (coefficient of variation, 4.1% and 3.3%). An association between less severe haze measurements and higher reproducibility scores was found (r = .42; P = .007). The mean interanalyzer variation was smaller for the average of four measurements, 0.55 +/- 0.37 gray levels, than for one measurement, 0.94 +/- 0.73 gray levels (P = .014). CONCLUSIONS Good reproducibility for haze measurements by digital image analysis of the differences between the treated and adjacent untreated corneal areas was obtained. When the average of four measurements was used instead of a single measurement, interanalyzer reproducibility increased significantly. This new technique may be used to quantify and analyze corneal haze after myopic photorefractive keratectomy.

Global patterns of sequence evolution in Drosophila

BackgroundSequencing of the genomes of several Drosophila allows for the first precise analyses of how global sequence patterns change among multiple, closely related animal species. A basic question is whether there are characteristic features that differentiate chromosomes within a species or between different species.ResultsWe explored the euchromatin of the chromosomes of seven Drosophila species to establish their global patterns of DNA sequence diversity. Between species, differences in the types and amounts of simple sequence repeats were found. Within each species, the autosomes have almost identical oligonucleotide profiles. However, X chromosomes and autosomes have, in all species, a qualitatively different composition. The X chromosomes are less complex than the autosomes, containing both a higher amount of simple DNA sequences and, in several cases, chromosome-specific repetitive sequences. Moreover, we show that the right arm of the X chromosome of Drosophila pseudoobscura, which evolved from an autosome 10 – 18 millions of years ago, has a composition which is identical to that of the original, left arm of the X chromosome.ConclusionThe consistent differences among species, differences among X chromosomes and autosomes and the convergent evolution of X and neo-X chromosomes demonstrate that strong forces are acting on drosophilid genomes to generate peculiar chromosomal landscapes. We discuss the relationships of the patterns observed with differential recombination and mutation rates and with the process of dosage compensation.

Reactome pathway analysis: a high-performance in-memory approach

BackgroundReactome aims to provide bioinformatics tools for visualisation, interpretation and analysis of pathway knowledge to support basic research, genome analysis, modelling, systems biology and education. Pathway analysis methods have a broad range of applications in physiological and biomedical research; one of the main problems, from the analysis methods performance point of view, is the constantly increasing size of the data samples.ResultsHere, we present a new high-performance in-memory implementation of the well-established over-representation analysis method. To achieve the target, the over-representation analysis method is divided in four different steps and, for each of them, specific data structures are used to improve performance and minimise the memory footprint. The first step, finding out whether an identifier in the user’s sample corresponds to an entity in Reactome, is addressed using a radix tree as a lookup table. The second step, modelling the proteins, chemicals, their orthologous in other species and their composition in complexes and sets, is addressed with a graph. The third and fourth steps, that aggregate the results and calculate the statistics, are solved with a double-linked tree.ConclusionThrough the use of highly optimised, in-memory data structures and algorithms, Reactome has achieved a stable, high performance pathway analysis service, enabling the analysis of genome-wide datasets within seconds, allowing interactive exploration and analysis of high throughput data. The proposed pathway analysis approach is available in the Reactome production web site either via the AnalysisService for programmatic access or the user submission interface integrated into the PathwayBrowser. Reactome is an open data and open source project and all of its source code, including the one described here, is available in the AnalysisTools repository in the Reactome GitHub (https://github.com/reactome/).

On the design of communication-aware task scheduling strategies for heterogeneous systems

Many research activities have focused on the problem of task scheduling in heterogeneous systems from the computational point of view. However an ideal scheduling strategy would also take into account the communication requirements of the applications and the communication bandwidth that the network can offer. In this paper, we first propose a criterion to measure the suitability of each allocation of network resources to each parallel application, according to the communication requirements. Second, we propose a scheduling technique based exclusively on this criterion that provides a near-optimal mapping of processes to processors according to the communication requirements. Evaluation results show that the use of this scheduling technique fully exploits the available network bandwidth, greatly improving network performance. Therefore, the proposed scheduling technique may be used in the design of communication-aware scheduling strategies for those situations where the communication requirements are the system performance bottleneck.

Acceleration of short and long DNA read mapping without loss of accuracy using suffix array

HPG Aligner applies suffix arrays for DNA read mapping. This implementation produces a highly sensitive and extremely fast mapping of DNA reads that scales up almost linearly with read length. The approach presented here is faster (over 20× for long reads) and more sensitive (over 98% in a wide range of read lengths) than the current state-of-the-art mappers. HPG Aligner is not only an optimal alternative for current sequencers but also the only solution available to cope with longer reads and growing throughputs produced by forthcoming sequencing technologies. Availability and implementation: https://github.com/opencb/hpg-aligner. Contact: jdopazo@cipf.es or imedina@ebi.ac.uk Supplementary information: Supplementary data are available at Bioinformatics online.

Characterization of communications between processes in message-passing applications

Many research activities have focused on the problem of task scheduling in heterogeneous systems from the computational point of view. However, an ideal scheduling strategy would also take into account the communication requirements of the applications and the communication bandwidth available in the network. One of the major problems to be solved in the development of this scheduling strategy is precisely the measurement of the communication requirements for each application. We propose a clustering-based method to characterize the communications between processes generated by message-passing applications. This technique provides a model consisting of several partitions of the processes generated by the application. Also, we propose a criterion to measure the quality of the obtained partitions. This approach can be used when a given application is repeatedly executed with different input data. Results show that the proposed method can provide a partition with the highest ratio between the intracluster and the intercluster required communication bandwidth. This partition can be used to map groups of processes to processors in the heterogeneous system.

Fast comparison of DNA sequences by oligonucleotide profiling

BackgroundThe comparison of DNA sequences is a traditional problem in genomics and bioinformatics. Many new opportunities emerge due to the improvement of personal computers, allowing the implementation of novel strategies of analysis.FindingsWe describe a new program, called UVWORD, which determines the number of times that each DNA word present in a sequence (target) is found in a second sequence (source), a procedure that we have called oligonucleotide profiling. On a standard computer, the user may search for words of a size ranging from k = 1 to k = 14 nucleotides. Average counts for groups of contiguous words may also be established. The rate of analysis on standard computers is from 3.4 (k = 14) to 16 millions of words per second (1 ≤ k ≤ 8). This makes feasible the fast screening of even the longest known DNA molecules.DiscussionWe show that the combination of the ability of analyzing words of relatively long size, which occur very rarely by chance, and the fast speed of the program allows to perform novel types of screenings, complementary to those provided by standard programs such as BLAST. This method can be used to determine oligonucleotide content, to characterize the distribution of repetitive sequences in chromosomes, to determine the evolutionary conservation of sequences in different species, to establish regions of similar DNA among chromosomes or genomes, etc.

A sequence motif enriched in regions bound by the Drosophila dosage compensation complex

BackgroundIn Drosophila melanogaster, dosage compensation is mediated by the action of the dosage compensation complex (DCC). How the DCC recognizes the fly X chromosome is still poorly understood. Characteristic sequence signatures at all DCC binding sites have not hitherto been found.ResultsIn this study, we compare the known binding sites of the DCC with oligonucleotide profiles that measure the specificity of the sequences of the D. melanogaster X chromosome. We show that the X chromosome regions bound by the DCC are enriched for a particular type of short, repetitive sequences. Their distribution suggests that these sequences contribute to chromosome recognition, the generation of DCC binding sites and/or the local spreading of the complex. Comparative data indicate that the same sequences may be involved in dosage compensation in other Drosophila species.ConclusionsThese results offer an explanation for the wild-type binding of the DCC along the Drosophila X chromosome, contribute to delineate the forces leading to the establishment of dosage compensation and suggest new experimental approaches to understand the precise biochemical features of the dosage compensation system.