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Showing papers by "José María Carazo published in 2009"


Journal ArticleDOI
TL;DR: A new version of the GeneCodis system has been developed, expanding the functional information with regulatory patterns and user-defined annotations, offering the possibility of integrating all sources of information in the same analysis.
Abstract: GeneCodis is a web server application for functional analysis of gene lists that integrates different sources of information and finds modular patterns of interrelated annotations. This integrative approach has proved to be useful for the interpretation of high-throughput experiments and therefore a new version of the system has been developed to expand its functionality and scope. GeneCodis now expands the functional information with regulatory patterns and user-defined annotations, offering the possibility of integrating all sources of information in the same analysis. Traditional singular enrichment is now permitted and more organisms and gene identifiers have been added to the database. The application has been re-engineered to improve performance, accessibility and scalability. In addition, GeneCodis can now be accessed through a public SOAP web services interface, enabling users to perform analysis from their own scripts and workflows. The application is freely available at http://genecodis.dacya.ucm.es

436 citations


Journal Article
TL;DR: Cheng et al. as mentioned in this paper reported that mice lacking asparaginyl endopeptidase develop disorders resembling hemophagocytic syndrome, and they added Chengyun Zheng, Jan-Inge Henter, Marie Meeths, and Magnus Nordenskjold to the authors list between Akitsugu Yamamoto and Shi-Yong Li.
Abstract: Correction for "Mice lacking asparaginyl endopeptidase develop disorders resembling hemophagocytic syndrome," by Chi-Bun Chan, Michivo Abe, Norivoshi Hashimoto, Chunhai Hao, Ifor R. Williams, Xia Liu, Shinji Nakao, Akitsugu Yamamoto, Shi-Yong Li, Ikuko Hara-Nishimura, Masahide Asano, and Keqiang Ye, which appeared in issue 2, January 13, 2009, of Proc NatlAcad Sci USA (106:468-473; first published December 23, 2008; 10.1073/pnas.0809824105). The authors request that Chengyun Zheng, Jan-Inge Henter, Marie Meeths, and Magnus Nordenskjold be added to the authors list between Akitsugu Yamamoto and Shi-Yong Li. Chengyun Zheng designed research and analyzed data, Jan-Inge Henter designed research, Marie Meeths performed research and analyzed data, and Magnus Nordenskjold analyzed data. The online version has been corrected. The corrected author and

134 citations


Journal ArticleDOI
TL;DR: The boundaries of the ATPase module in the “base” part of the regulatory complex that can vary in its position and orientation relative to the 20S core particle are outlined.
Abstract: Cryo-electron microscopy in conjunction with advanced image analysis was used to analyze the structure of the 26S proteasome and to elucidate its variable features. We have been able to outline the boundaries of the ATPase module in the “base” part of the regulatory complex that can vary in its position and orientation relative to the 20S core particle. This variation is consistent with the “wobbling” model that was previously proposed to explain the role of the regulatory complex in opening the gate in the α-rings of the core particle. In addition, a variable mass near the mouth of the ATPase ring has been identified as Rpn10, a multiubiquitin receptor, by correlating the electron microscopy data with quantitative mass spectrometry.

128 citations


Journal ArticleDOI
TL;DR: A maximum likelihood algorithm is presented for the simultaneous alignment and classification of subtomograms or random conical tilt (RCT) reconstructions, where the Fourier components in the missing data regions are treated as hidden variables.

113 citations


Journal ArticleDOI
TL;DR: An algorithm is able to correctly align a single-tilt tomographic series without the help of fiducial markers thanks to the detection of thousands of small image patches that can be tracked over a short number of images in the series.
Abstract: Background Tilt series are commonly used in electron tomography as a means of collecting three-dimensional information from two-dimensional projections. A common problem encountered is the projection alignment prior to 3D reconstruction. Current alignment techniques usually employ gold particles or image derived markers to correctly align the images. When these markers are not present, correlation between adjacent views is used to align them. However, sequential pairwise correlation is prone to bias and the resulting alignment is not always optimal.

104 citations


Journal ArticleDOI
TL;DR: Centrosome:db is presented, which intends to compile and integrate relevant information related to the human centrosome, which contains information on the orthology relationships with other species, including fungi, nematodes, arthropods, urochordates and vertebrates.
Abstract: Active research on the biology of the centrosome during the past decades has allowed the identification and characterization of many centrosomal proteins. Unfortunately, the accumulated data is still dispersed among heterogeneous sources of information. Here we present centrosome:db, which intends to compile and integrate relevant information related to the human centrosome. We have compiled a set of 383 likely human centrosomal genes and recorded the associated supporting evidences. Centrosome:db offers several perspectives to study the human centrosome including evolution, function and structure. The database contains information on the orthology relationships with other species, including fungi, nematodes, arthropods, urochordates and vertebrates. Predictions of the domain organization of centrosome:db proteins are graphically represented at different sections of the database, including sets of alternative protein isoforms, interacting proteins, groups of orthologs and the homologs identified with blast. Centrosome:db also contains information related to function, gene-disease associations, SNPs and the 3D structure of proteins. Apart from important differences in the coverage of the set of centrosomal genes, our database differentiates from other similar initiatives in the way information is treated and analyzed. Centrosome:db is publicly available at http://centrosome.dacya.ucm.es.

80 citations


Journal ArticleDOI
TL;DR: This paper introduces a new automatic particle selection that learns from the user which particles are of interest and is able to produce datasets with fewer wrongly selected particles than previously reported methods.

68 citations


Journal ArticleDOI
TL;DR: This contribution compared two different approaches to explore the flexibility space of protein domains: i) molecular dynamics (MD-space), and ii) the study of the structural changes within superfamily (SF-space).
Abstract: It is well known the strong relationship between protein structure and flexibility, on one hand, and biological protein function, on the other hand Technically, protein flexibility exploration is an essential task in many applications, such as protein structure prediction and modeling In this contribution we have compared two different approaches to explore the flexibility space of protein domains: i) molecular dynamics (MD-space), and ii) the study of the structural changes within superfamily (SF-space) Our analysis indicates that the MD-space and the SF-space display a significant overlap, but are still different enough to be considered as complementary The SF-space space is wider but less complex than the MD-space, irrespective of the number of members in the superfamily Also, the SF-space does not sample all possibilities offered by the MD-space, but often introduces very large changes along just a few deformation modes, whose number tend to a plateau as the number of related folds in the superfamily increases Theoretically, we obtained two conclusions First, that function restricts the access to some flexibility patterns to evolution, as we observe that when a superfamily member changes to become another, the path does not completely overlap with the physical deformability Second, that conformational changes from variation in a superfamily are larger and much simpler than those allowed by physical deformability Methodologically, the conclusion is that both spaces studied are complementary, and have different size and complexity We expect this fact to have application in fields as 3D-EM/X-ray hybrid models or ab initio protein folding

38 citations


Journal ArticleDOI
TL;DR: A statistical data model that accounts for normalization errors is presented, and a corresponding algorithm for maximum likelihood classification of structurally heterogeneous projection data is derived.

35 citations


Proceedings ArticleDOI
05 Jun 2009
TL;DR: A system that uses the case-based reasoning (CBR) machine learning approach for the extraction of the entities (events, sites and location) and achieves an f-measure of 24.15 and 21.15 for Task 1 and 2, respectively.
Abstract: The BioNLP'09 Shared Task on Event Extraction presented an evaluation on the extraction of biological events related to genes/proteins from the literature. We propose a system that uses the case-based reasoning (CBR) machine learning approach for the extraction of the entities (events, sites and location). The mapping of the proteins in the texts to the previously extracted entities is carried out by some simple manually developed rules for each of the arguments under consideration (cause, theme, site or location). We have achieved an f-measure of 24.15 and 21.15 for Task 1 and 2, respectively.

22 citations


Journal ArticleDOI
TL;DR: A parallel implementation of a computation-intensive algorithm for three-dimensional reconstruction, ART, that takes advantage of the computational power in modern multicore platforms is proposed.

Journal ArticleDOI
TL;DR: Which are the most sensitive CTF parameters as well as the mostsensitive background parameters and a methodology to reveal the internal structure of the CTF model and to estimate the accuracy of each model parameter are provided.
Abstract: Background The transmission electron microscope is used to acquire structural information of macromolecular complexes. However, as any other imaging device, it introduces optical aberrations that must be corrected if high-resolution structural information is to be obtained. The set of all aberrations are usually modeled in Fourier space by the so-called Contrast Transfer Function (CTF). Before correcting for the CTF, we must first estimate it from the electron micrographs. This is usually done by estimating a number of parameters specifying a theoretical model of the CTF. This estimation is performed by minimizing some error measure between the theoretical Power Spectrum Density (PSD) and the experimentally observed PSD. The high noise present in the micrographs, the possible local minima of the error function for estimating the CTF parameters, and the cross-talking between CTF parameters may cause errors in the estimated CTF parameters.

Journal ArticleDOI
TL;DR: SENT uses Non-negative Matrix Factorization to identify topics in the scientific articles related to a collection of genes or their products, and use them to group and summarize these genes.
Abstract: We present SENT (semantic features in text), a functional interpretation tool based on literature analysis. SENT uses Non-negative Matrix Factorization to identify topics in the scientific articles related to a collection of genes or their products, and use them to group and summarize these genes. In addition, the application allows users to rank and explore the articles that best relate to the topics found, helping put the analysis results into context. This approach is useful as an exploratory step in the workflow of interpreting and understanding experimental data, shedding some light into the complex underlying biological mechanisms. This tool provides a user-friendly interface via a web site, and a programmatic access via a SOAP web server. SENT is freely accessible at http://sent.dacya.ucm.es.

Journal ArticleDOI
TL;DR: This paper shows how to compute the normalizing and the system matrix terms of the EM-ML reconstruction algorithm for rotating planar detector PET scanners and shows that the computations are comparable to those of a Monte Carlo method at a small fraction of the computational cost.
Abstract: In this paper we show how to compute the normalizing and the system matrix terms of the EM-ML reconstruction algorithm for rotating planar detector PET scanners. The method introduced is valid for either pixelated or continuous scintillators. We base our computations in geometrical considerations, but other effects of the PET process can be easily included. In this regard, the intrinsic resolution of the detection system, the depth of interaction (DOI) of the incident gamma rays and the efficiency of the scintillators have been modeled in our development. The computation of the normalizing term and the system matrix is valid for any basis function used for the discrete approximation of the radionuclide concentration. We show that our computations are comparable to those of a Monte Carlo method at a small fraction of the computational cost.

Journal ArticleDOI
TL;DR: An expectation-maximization algorithm for maximum-likelihood refinement of electron-microscopy data is presented that is based on finite mixtures of multivariate t-distributions that provides robustness against outliers in the data.
Abstract: An expectation-maximization algorithm for maximum-likelihood refinement of electron-microscopy images is presented that is based on fitting mixtures of multivariate t-distributions. The novel algorithm has intrinsic characteristics for providing robustness against atypical observations in the data, which is illustrated using an experimental test set with artificially generated outliers. Tests on experimental data revealed only minor differences in two-dimensional classifications, while three-dimensional classification with the new algorithm gave stronger elongation factor G density in the corresponding class of a structurally heterogeneous ribosome data set than the conventional algorithm for Gaussian mixtures.

Journal ArticleDOI
TL;DR: The aGEM Platform has been built by extending the Distributed Annotation System (DAS) protocol, which was originally designed to share genome annotations over the WWW, to integrate phenotypic information with the spatial and temporal distributions of genes expressed in the mouse.
Abstract: Motivation: The work presented here describes the ‘anatomical Gene-Expression Mapping (aGEM)’ Platform, a development conceived to integrate phenotypic information with the spatial and temporal distributions of genes expressed in the mouse. The aGEM Platform has been built by extending the Distributed Annotation System (DAS) protocol, which was originally designed to share genome annotations over the WWW. DAS is a client-server system in which a single client integrates information from multiple distributed servers. Results: The aGEM Platform provides information to answer three main questions. (i) Which genes are expressed in a given mouse anatomical component? (ii) In which mouse anatomical structures are a given gene or set of genes expressed? And (iii) is there any correlation among these findings? Currently, this Platform includes several well-known mouse resources (EMAGE, GXD and GENSAT), hosting gene-expression data mostly obtained from in situ techniques together with a broad set of image-derived annotations. Availability: The Platform is optimized for Firefox 3.0 and it is accessed through a friendly and intuitive display: http://agem.cnb.csic.es Contact: se.cisc.bnc@ailatan Supplementary information: Supplementary data are available at http://bioweb.cnb.csic.es/VisualOmics/aGEM/home.html and http://bioweb.cnb.csic.es/VisualOmics/index_VO.html and Bioinformatics online.

Proceedings ArticleDOI
13 Oct 2009
TL;DR: The electron microscopy community has paid little attention to this step assuming that even a trivial filter, as "bining" does not affect the posterior image processing steps as mentioned in this paper, and this hypothesis is not correct.
Abstract: Electron microscopy of single particles aims at the elucidation of the three-dimensional structure of macromolecular complexes. This information is crucial for the more complete understanding of how these nanomachines perform their functions in the cell. Electron microscopy images are recorded in digital form at a resolution much higher than needed from the signal theory point of view. Then, they are downsampled to the required resolution. The electron microscopy community has paid little attention to this step assuming that even a trivial filter, as ”bining”, does not affect the posterior image processing steps. In this paper we show that this hypothesis is not correct.

Book ChapterDOI
28 Jun 2009
TL;DR: Moara, a Java library that implements gene/protein recognition and normalization steps based on machine learning approaches, and the novelty of the methodology used in Moara lies in the design of a system that does not need any organism-dependent tuning in the algorithms and in the dictionaries it uses.
Abstract: Gene/protein recognition and normalization are important prerequisite steps for many biological text mining tasks. Even if great efforts have been dedicated to these problems and effective solutions have been reported, the availability of easily integrated tools to perform these tasks is still deficient. We therefore propose Moara, a Java library that implements gene/protein recognition and normalization steps based on machine learning approaches. The system may be trained with extra documents for the recognition procedure and new organism may be added in the normalization step. The novelty of the methodology used in Moara lies in the design of a system that is not tailored to a specific organism and therefore does not need any organism-dependent tuning in the algorithms and in the dictionaries it uses. Moara can be used either as a standalone application or incorporated in a text mining system and it is available at: http://moara.dacya.ucm.es