Paulo Nuin › Comments

Agora vai! - Paulo Nuin

no access here - Pedro Matos

Thanks for the hard work guys- I am a bit new to all this. And a very heavy teaching load at the moment (always excuses!!!) The e-mail is correct though Graeme. Cheers :-) - DrNoelCarter

Are you working at Amazon as well? - Hari

Nope, no Amazon for me. But this is something we already (Jan Aerts at least) discussed that would be a good idea (some "free" time to test and see if you like the service). - Paulo Nuin

Oikos, Vol. 116, No. 5. (May 2007), pp. 723-727. Kaj Sand-Jensen - Paulo Nuin

Genome Biology, Vol. 10, No. 3. (2009), R25. Bowtie is an ultrafast, memory-efficient alignment program for aligning short DNA sequence reads to large genomes. For the human genome, Burrows-Wheeler indexing allows Bowtie to align more than 25 million reads per CPU hour with a memory footprint of approximately 1.3 gigabytes. Bowtie extends previous Burrows-Wheeler techniques with a novel quality-aware backtracking algorithm that permits mismatches. Multiple processor cores can be used simultaneously to achieve even greater alignment speeds. Bowtie is open source http://bowtie.cbcb.umd.edu. Ben Langmead, Cole Trapnell, Mihai Pop, Steven Salzberg - Paulo Nuin

Nature Biotechnology, Vol. 27, No. 8. (07 August 2009), pp. 735-741. Circuit diagrams and Unified Modeling Language diagrams are just two examples of standard visual languages that help accelerate work by promoting regularity, removing ambiguity and enabling software tool support for communication of complex information. Ironically, despite having one of the highest ratios of graphical to textual information, biology still lacks standard graphical notations. The recent deluge of biological knowledge makes addressing this deficit a pressing concern. Toward this goal, we present the Systems Biology Graphical Notation (SBGN), a visual language developed by a community of biochemists, modelers and computer scientists. SBGN consists of three complementary languages: process diagram, entity relationship diagram and activity flow diagram. Together they enable scientists to represent networks of biochemical interactions in a standard, unambiguous way. We believe that SBGN will foster... - Paulo Nuin

Bioinformatics, Vol. 25, No. 15. (1 August 2009), pp. 1966-1967. Summary: SOAP2 is a significantly improved version of the short oligonucleotide alignment program that both reduces computer memory usage and increases alignment speed at an unprecedented rate. We used a Burrows Wheeler Transformation (BWT) compression index to substitute the seed strategy for indexing the reference sequence in the main memory. We tested it on the whole human genome and found that this new algorithm reduced memory usage from 14.7 to 5.4 GB and improved alignment speed by 20-30 times. SOAP2 is compatible with both single- and paired-end reads. Additionally, this tool now supports multiple text and compressed file formats. A consensus builder has also been developed for consensus assembly and SNP detection from alignment of short reads on a reference genome. Availability: http://soap.genomics.org.cn Contact: soap@genomics.org.cn 10.1093/bioinformatics/btp336 Ruiqiang Li, Chang Yu, Yingrui Li, Tak-Wah Lam,... - Paulo Nuin

[Found via Brian Yohn] Be sure to read the superb reviews and view the user contributed pictures. Pure gold. - Chris Lasher from Bookmarklet

I guess you need to close the lid to honk, right? - Paulo Nuin

Depends on how firm a screen your laptop has. I'd say you could go ahead and just lay down on the horn through a Thinkpad. ;-) - Chris Lasher

Ok if I comment here ? http://friendfeed.com/sciphu... - Nils Reinton

That's true - I probably should have asked about that - didn't occur to me at the time... - Cameron Neylon

It's about once every other day for me :( - Brian Krueger - LabSpaces

Wait until Jan 1st, and then you'll see. - Paulo Nuin

Bioinformatics (Oxford, England) (21 October 2009), btp603. MOTIVATION: Chromosomal aberrations tend to be characteristic for given (sub) types of cancer. Such aberrations can be detected with array Comparative Genomic Hybridization (aCGH). Clustering aCGH tumor profiles aids in identifying chromosomal regions of interest and provides useful diagnostic information on the cancer type. An important issue here is to what extent individual aCGH tumor profiles can be reliably assigned to clusters associated with a given cancer type. RESULTS: We introduce a novel evolutionary fuzzy clustering (EFC) algorithm, which is able to deal with overlapping clusterings. Our method assesses these overlaps by using cluster membership degrees, which we use here as a confidence measure for individual samples to be assigned to a given tumor type. We first demonstrate the usefulness of our method using a synthetic aCGH dataset and subsequently show that EFC outperforms existing methods on four real... - Paulo Nuin

Journal of molecular evolution (23 October 2009) Testing fit of data to model is fundamentally important to any science, but publications in the field of phylogenetics rarely do this. Such analyses discard fundamental aspects of science as prescribed by Karl Popper. Indeed, not without cause, Popper (Unended quest: an intellectual autobiography. Fontana, London, 1976) once argued that evolutionary biology was unscientific as its hypotheses were untestable. Here we trace developments in assessing fit from Penny et al. (Nature 297:197-200, 1982) to the present. We compare the general log-likelihood ratio (the G or G (2) statistic) statistic between the evolutionary tree model and the multinomial model with that of marginalized tests applied to an alignment (using placental mammal coding sequence data). It is seen that the most general test does not reject the fit of data to model (P ~ 0.5), but the marginalized tests do. Tests on pairwise frequency (F) matrices, strongly (P < 0.001)... - Paulo Nuin

Nature genetics, Vol. 41, No. 10. (01 October 2009), pp. 1045-1045. Datasets released to public databases in advance of (or with) research publications should be given digital object identifiers to allow databases and journals to give quantitative citation credit to the data producers and curators. - Paulo Nuin

Bioinformatics (Oxford, England), Vol. 25, No. 23. (1 December 2009), pp. 3151-3157. MOTIVATION: For the early detection of cancer, highly sensitive and specific biomarkers are needed. Particularly, biomarkers in bio-fluids are relatively more useful because those can be used for non-biopsy tests. Although the altered metabolic activities of cancer cells have been observed in many studies, little is known about metabolic biomarkers for cancer screening. In this study, a systematic method is proposed for identifying metabolic biomarkers in urine samples by selecting candidate biomarkers from altered genome-wide gene expression signatures of cancer cells. Biomarkers identified by the present study have increased coherence and robustness because the significances of biomarkers are validated in both gene expression profiles and metabolic profiles. RESULTS: The proposed method was applied to the gene expression profiles and urine samples of 50 breast cancer patients and 50 normal persons.... - Paulo Nuin

BMC Bioinformatics, Vol. 10, No. 1. (15 October 2009), 337. BACKGROUND:Classification using microarray datasets is usually based on a small number of samples for which tens of thousands of gene expression measurements have been obtained. The selection of the genes most significant to the classification problem is a challenging issue in high dimension data analysis and interpretation. A previous study with SVM-RCE (Recursive Cluster Elimination), suggested that classification based on groups of correlated genes sometimes exhibits better performance than classification using single genes. Large databases of gene interaction networks provide an important resource for the analysis of genetic phenomena and for classification studies using interacting genes.We now demonstrate that an algorithm which integrates network information with recursive feature elimination based on SVM exhibits good performance and improves the biological interpretability of the results. We refer to the method as... - Paulo Nuin

Bioinformatics (Oxford, England) (9 October 2009) MOTIVATION: The need to align spectra to correct for mass-to-charge experimental variation is a problem that arises in mass spectrometry (MS). Most MS-based proteomic data analysis methods involve a two-step approach, identify peaks first and then do the alignment and statistical inference on these identified peaks only. However, the peak identification step relies on prior information on the proteins of interest or a peak detection model, which are subject to error. Also numerous additional features such as peak shape and peak width are lost in simple peak detection, and these are informative for correcting mass variation in the alignment step. RESULTS: Here we present a novel Bayesian approach to align the complete spectra. The approach is based on a parametric model which assumes the spectrum and alignment function are Gaussian processes, but the alignment function is monotone. We show how to use the expectation-maximization... - Paulo Nuin

BMC Bioinformatics, Vol. 10, No. 1. (9 September 2009), 283. BACKGROUND:We propose an efficient and biologically sensitive algorithm based on repeated random walks (RRW) for discovering functional modules, e.g., complexes and pathways, within large-scale protein networks. Compared to existing cluster identification techniques, RRW implicitly makes use of network topology, edge weights, and long range interactions between proteins.RESULTS:We apply the proposed technique on a functional network of yeast genes and accurately identify statistically significant clusters of proteins. We validate the biological significance of the results using known complexes in the MIPS complex catalogue database and well-characterized biological processes. We find that 90% of the created clusters have the majority of their catalogued proteins belonging to the same MIPS complex, and about 80% have the majority of their proteins involved in the same biological process. We compare our method to various other... - Paulo Nuin

Bioinformatics (Oxford, England) (24 October 2009), btp611. SUMMARY: High-throughput sequencing technologies introduce novel demands on tools available for data analysis. We have developed NGSView, a generally applicable, flexible and extensible next-generation sequence alignment editor. The software allows for visualization and manipulation of millions of sequences simultaneously on a desktop computer, through a graphical interface. NGSView is available under an open source license and can be extended through a well documented API. AVAILABILITY: http://ngsview.sourceforge.net CONTACT: arner@gsc.riken.jp. Erik Arner, Yoshihide Hayashizaki, Carsten Daub - Paulo Nuin

BMC Bioinformatics, Vol. 10, No. 1. (2009), 330. BACKGROUND:Microarray experiments are increasing in size and samples are collected asynchronously over long time. Available data are re-analysed as more samples are hybridized. Systematic use of collected data requires tracking of biomaterials, array information, raw data, and assembly of annotations. To meet the information tracking and data analysis challenges in microarray experiments we reimplemented and improved BASE version 1.2.RESULTS:The new BASE presented in this report is a comprehensive annotable local microarray data repository and analysis application providing researchers with an efficient information management and analysis tool. The information management system tracks all material from biosource, via sample and through extraction and labelling to raw data and analysis. All items in BASE can be annotated and the annotations can be used as experimental factors in downstream analysis. BASE stores all microarray experiment... - Paulo Nuin

BMC Bioinformatics, Vol. 10, No. 1. (7 October 2009), 321. BACKGROUND:Identification of transcription factor binding sites (TFBSs) is a central problem in Bioinformatics on gene regulation. de novo motif discovery serves as a promising way to predict and better understand TFBSs for biological verifications. Real TFBSs of a motif may vary in their widths and their conservation degrees within a certain range. Deciding a single motif width by existing models may be biased and misleading. Additionally, multiple, possibly overlapping, candidate motifs are desired and necessary for biological verification in practice. However, current techniques either prohibit overlapping TFBSs or lack explicit control of different motifs.RESULTS:We propose a new generalized model to tackle the motif widths by considering and evaluating a width range of interest simultaneously, which should better address the width uncertainty. Moreover, a meta-convergence framework for genetic algorithms (GAs), is... - Paulo Nuin

BMC Bioinformatics, Vol. 10, No. 1. (2009), 356. BACKGROUND:Evolutionary trees are central to a wide range of biological studies. In many of these studies, tree nodes and branches need to be associated (or annotated) with various attributes. For example, in studies concerned with organismal relationships, tree nodes are associated with taxonomic names, whereas tree branches have lengths and oftentimes support values. Gene trees used in comparative genomics or phylogenomics are usually annotated with taxonomic information, genome-related data, such as gene names and functional annotations, as well as events such as gene duplications, speciations, or exon shufflings, combined with information related to the evolutionary tree itself. The data standards currently used for evolutionary trees have limited capacities to incorporate such annotations of different data types.RESULTS:We developed a XML language, named phyloXML, for describing evolutionary trees, as well as various associated... - Paulo Nuin

Bioinformatics (Oxford, England) (22 October 2009), btp608. MOTIVATION: By default, the R statistical environment does not make use of parallelism. Researchers may resort to expensive solutions such as cluster hardware for large analysis tasks. Graphics processing units (GPUs) provide an inexpensive and computationally powerful alternative. Using R and the CUDA toolkit from Nvidia, we have implemented several functions commonly used in microarray gene expression analysis for GPU equipped computers. RESULTS: R users can take advantage of the better performance provided by an Nvidia GPU. AVAILABILITY: The package is available from CRAN, the R project's repository of packages, at http://cran.r-project.org/web... More information about our gputools R package is available at http://brainarray.mbni.med.umich.edu/brainar... CONTACT: bucknerj@umich.edu. Joshua Buckner, Justin Wilson, Mark Seligman, Brian Athey, Stanley Watson, Fan Meng - Paulo Nuin

Bioinformatics (Oxford, England), Vol. 25, No. 23. (1 December 2009), pp. 3128-3134. MOTIVATION: The goal of present -omics sciences is to understand biological systems as a whole in terms of interactions of the individual cellular components. One of the main building blocks in this field of study is proteomics where tandem mass spectrometry (LC-MS/MS) in combination with isotopic labelling techniques provides a common way to obtain a direct insight into regulation at the protein level. Methods to identify and quantify the peptides contained in a sample are well established, and their output usually results in lists of identified proteins and calculated relative abundance values. The next step is to move ahead from these abstract lists and apply statistical inference methods to compare measurements, to identify genes that are significantly up- or down-regulated, or to detect clusters of proteins with similar expression profiles. RESULTS: We introduce the Rich Internet Application... - Paulo Nuin

BMC Bioinformatics, Vol. 10, No. 1. (2009), 342. BACKGROUND:Isobaric Tags for Relative and Absolute Quantitation (iTRAQTM) [Applied Biosystems] have seen increased application in differential protein expression analysis. To facilitate the growing need to analyze iTRAQ data, especially for cases involving multiple iTRAQ experiments, we have developed a modeling approach, statistical methods, and tools for estimating the relative changes in protein expression under various treatments and experimental conditions.RESULTS:This modeling approach provides a unified analysis of data from multiple iTRAQ experiments and links the observed quantity (reporter ion peak area) to the experiment design and the calculated quantity of interest (treatment-dependent protein and peptide fold change) through an additive model under log transformation. Others have demonstrated, through a case study, this modeling approach and noted the computational challenges of parameter inference in the unbalanced data... - Paulo Nuin

BMC Bioinformatics, Vol. 10, No. 1. (16 October 2009), 339. BACKGROUND:It is known that transcription factors frequently act together to regulate gene expression in eukaryotes. In this paper we describe a computational analysis of transcription factor site dependencies in human, mouse and rat genomes.RESULTS:Our approach for quantifying tendencies of transcription factor binding sites to co-occur is based on a binding site scoring function which incorporates dependencies between positions, the use of information about the structural class of each transcription factor (major/minor groove binder), and also considered the possible implications of varying GC content of the sequences. Significant tendencies (dependencies) have been detected by non-parametric statistical methodology (permutation tests). Evaluation of obtained results has been performed in several ways: reports from literature (many of the significant dependencies between transcription factors have previously been confirmed... - Paulo Nuin

BMC Bioinformatics, Vol. 10, No. 1. (7 October 2009), 320. BACKGROUND:The rapid evolution of Internet technologies and the collaborative approaches that dominate the field have stimulated the development of numerous bioinformatics resources. To address this new framework, several initiatives have tried to organize these services and resources. In this paper, we present the BioInformatics Resource Inventory (BIRI), a new approach for automatically discovering and indexing available public bioinformatics resources using information extracted from the scientific literature. The index generated can be automatically updated by adding additional manuscripts describing new resources. We have developed web services and applications to test and validate our approach. It has not been designed to replace current indexes but to extend their capabilities with richer functionalities.RESULTS:We developed a web service to provide a set of high-level query primitives to access the index. The web... - Paulo Nuin

BMC Bioinformatics, Vol. 10, No. 1. (2009), 316. BACKGROUND:The development of effective environmental shotgun sequence binning methods remains an ongoing challenge in algorithmic analysis of metagenomic data. While previous methods have focused primarily on supervised learning involving extrinsic data, a first-principles statistical model combined with a self-training fitting method has not yet been developed.RESULTS:We derive an unsupervised, maximum-likelihood formalism for clustering short sequences by their taxonomic origin on the basis of their k-mer distributions. The formalism is implemented using a Markov Chain Monte Carlo approach in a k-mer feature space. We introduce a space transformation that reduces the dimensionality of the feature space and a genomic fragment divergence measure that strongly correlates with the method's performance. Pairwise analysis of over 1000 completely sequenced genomes reveals that the vast majority of genomes have sufficient genomic fragment... - Paulo Nuin

Nucleic acids research (13 October 2009), gkp813. The local false discovery rate (LFDR) estimates the probability of falsely identifying specific genes with changes in expression. In computer simulations, LFDR <10% successfully identified genes with changes in expression, while LFDR >90% identified genes without changes. We used LFDR to compare different microarray experiments quantitatively: (i) Venn diagrams of genes with and without changes in expression, (ii) scatter plots of the genes, (iii) correlation coefficients in the scatter plots and (iv) distributions of gene function. To illustrate, we compared three methods for pre-processing microarray data. Correlations between methods were high (r = 0.84-0.92). However, responses were often different in magnitude, and sometimes discordant, even though the methods used the same raw data. LFDR complements functional assessments like gene set enrichment analysis. To illustrate, we compared responses to ultraviolet radiation (UV),... - Paulo Nuin

Trends in genetics : TIG, Vol. 25, No. 10. (30 October 2009), pp. 443-454. Duplicated sequences are substrates for the emergence of new genes and are an important source of genetic instability associated with rare and common diseases. Analyses of primate genomes have shown an increase in the proportion of interspersed segmental duplications (SDs) within the genomes of humans and great apes. This contrasts with other mammalian genomes that seem to have their recently duplicated sequences organized in a tandem configuration. In this review, we focus on the mechanistic origin and impact of this difference with respect to evolution, genetic diversity and primate phenotype. Although many genomes will be sequenced in the future, resolution of this aspect of genomic architecture still requires high quality sequences and detailed analyses. Tomas Marques-Bonet, Santhosh Girirajan, Evan Eichler - Paulo Nuin

Trends in genetics : TIG, Vol. 25, No. 10. (08 October 2009), pp. 455-462. Advances in genomic technologies have made it possible to screen the entire cancer genome for mutations, leading to a better understanding of the genetic landscape of cancer. Emerging results suggest that the cancer genome is composed of a few commonly mutated genes and many infrequently mutated genes. Although the number of mutated genes in any one tumor is limited, there is much heterogeneity in the genes mutated in two tumors of even the same class because of the large number of infrequently mutated genes. This could explain the wide variation in tumor behavior to chemotherapeutic intervention. Pathway analysis suggests this large collection of cancer genes functions in a few signaling pathways, providing a simplifying picture of cancer, and indicating the possibility of treating cancer using target-based therapeutics directed against the deregulated signaling pathways themselves rather than the individually... - Paulo Nuin