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  • Articles  (16)
  • Oxford University Press  (16)
  • American Physical Society (APS)
  • National Academy of Sciences
  • Bioinformatics  (6)
  • 2184
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  • Articles  (16)
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  • Oxford University Press  (16)
  • American Physical Society (APS)
  • National Academy of Sciences
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  • 1
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    repgenHMM: a dynamic programming tool to infer the rules of immune receptor generation from sequence data (2016)
    Oxford University Press
    Details
    Publication Date: 2016-06-25
    Description: Motivation : The diversity of the immune repertoire is initially generated by random rearrangements of the receptor gene during early T and B cell development. Rearrangement scenarios are composed of random events—choices of gene templates, base pair deletions and insertions—described by probability distributions. Not all scenarios are equally likely, and the same receptor sequence may be obtained in several different ways. Quantifying the distribution of these rearrangements is an essential baseline for studying the immune system diversity. Inferring the properties of the distributions from receptor sequences is a computationally hard problem, requiring enumerating every possible scenario for every sampled receptor sequence. Results : We present a Hidden Markov model, which accounts for all plausible scenarios that can generate the receptor sequences. We developed and implemented a method based on the Baum–Welch algorithm that can efficiently infer the parameters for the different events of the rearrangement process. We tested our software tool on sequence data for both the alpha and beta chains of the T cell receptor. To test the validity of our algorithm, we also generated synthetic sequences produced by a known model, and confirmed that its parameters could be accurately inferred back from the sequences. The inferred model can be used to generate synthetic sequences, to calculate the probability of generation of any receptor sequence, as well as the theoretical diversity of the repertoire. We estimate this diversity to be 1023 for human T cells. The model gives a baseline to investigate the selection and dynamics of immune repertoires. Availability and implementation : Source code and sample sequence files are available at https://bitbucket.org/yuvalel/repgenhmm/downloads . Contact: elhanati@lpt.ens.fr or tmora@lps.ens.fr or awalczak@lpt.ens.fr
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
    Published by Oxford University Press
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  • 2
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    Dragon TIS Spotter: an Arabidopsis-derived predictor of translation initiation sites in plants (2012)
    Oxford University Press
    Details
    Publication Date: 2012-12-21
    Description: : In higher eukaryotes, the identification of translation initiation sites (TISs) has been focused on finding these signals in cDNA or mRNA sequences. Using Arabidopsis thaliana ( A.t. ) information, we developed a prediction tool for signals within genomic sequences of plants that correspond to TISs. Our tool requires only genome sequence, not expressed sequences. Its sensitivity/specificity is for A.t. (90.75%/92.2%), for Vitis vinifera (66.8%/94.4%) and for Populus trichocarpa (81.6%/94.4%), which suggests that our tool can be used in annotation of different plant genomes. We provide a list of features used in our model. Further study of these features may improve our understanding of mechanisms of the translation initiation. Availability and implementation: Our tool is implemented as an artificial neural network. It is available as a web-based tool and, together with the source code, the list of features, and data used for model development, is accessible at http://cbrc.kaust.edu.sa/dts . Contact: vladimir.bajic@kaust.edu.sa Supplementary information : Supplementary data are available at Bioinformatics online.
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    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
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  • 3
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    JSpeciesWS: a web server for prokaryotic species circumscription based on pairwise genome comparison (2016)
    Oxford University Press
    Details
    Publication Date: 2016-03-16
    Description: : JSpecies Web Server (JSpeciesWS) is a user-friendly online service for in silico calculating the extent of identity between two genomes, a parameter routinely used in the process of polyphasic microbial species circumscription. The service measures the average nucleotide identity (ANI) based on BLAST+ (ANIb) and MUMmer (ANIm), as well as correlation indexes of tetra-nucleotide signatures (Tetra). In addition, it provides a Tetra Correlation Search function, which allows to rapidly compare selected genomes against a continuously updated reference database with currently about 32 000 published whole and draft genome sequences. For comparison, own genomes can be uploaded and references can be selected from the JSpeciesWS reference database. The service indicates whether two genomes share genomic identities above or below the species embracing thresholds, and serves as a fast way to allocate unknown genomes in the frame of the hitherto sequenced species. Availability and implementation: JSpeciesWS is available at http://jspecies.ribohost.com/jspeciesws . Supplementary information : Supplementary data are available at Bioinformatics online. Contact: mrichter@ribocon.com
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    Topics: Biology , Computer Science , Medicine
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  • 4
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    DOMINO: development of informative molecular markers for phylogenetic and genome-wide population genetic studies in non-model organisms (2016)
    Oxford University Press
    Details
    Publication Date: 2016-12-20
    Description: Motivation: The development of molecular markers is one of the most important challenges in phylogenetic and genome wide population genetics studies, especially in studies with non-model organisms. A highly promising approach for obtaining suitable markers is the utilization of genomic partitioning strategies for the simultaneous discovery and genotyping of a large number of markers. Unfortunately, not all markers obtained from these strategies provide enough information for solving multiple evolutionary questions at a reasonable taxonomic resolution. Results: We have developed Development Of Molecular markers In Non-model Organisms (DOMINO), a bioinformatics tool for informative marker development from both next generation sequencing (NGS) data and pre-computed sequence alignments. The application implements popular NGS tools with new utilities in a highly versatile pipeline specifically designed to discover or select personalized markers at different levels of taxonomic resolution. These markers can be directly used to study the taxa surveyed for their design, utilized for further downstream PCR amplification in a broader set taxonomic scope, or exploited as suitable templates to bait design for target DNA enrichment techniques. We conducted an exhaustive evaluation of the performance of DOMINO via computer simulations and illustrate its utility to find informative markers in an empirical dataset. Availability and Implementation: DOMINO is freely available from www.ub.edu/softevol/domino . Contact: elsanchez@ub.edu or jrozas@ub.edu Supplementary information: Supplementary data are available at Bioinformatics online.
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    Topics: Biology , Computer Science , Medicine
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  • 5
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    CellAging: a tool to study segregation and partitioning in division in cell lineages of Escherichia coli (2013)
    Oxford University Press
    Details
    Publication Date: 2013-06-24
    Description: Motivation: Cell division in Escherichia coli is morphologically symmetric. However, as unwanted protein aggregates are segregated to the cell poles and, after divisions, accumulate at older poles, generate asymmetries in sister cells’ vitality. Novel single-molecule detection techniques allow observing aging-related processes in vivo , over multiple generations, informing on the underlying mechanisms. Results: CellAging is a tool to automatically extract information on polar segregation and partitioning in division of aggregates in E.coli , and on cellular vitality. From time-lapse, parallel brightfield and fluorescence microscopy images, it performs cell segmentation, alignment of brightfield and fluorescence images, lineage construction and pole age determination, and it computes aging-related features. We exemplify its use by analyzing spatial distributions of fluorescent protein aggregates from images of cells across generations. Availability: CellAging, instructions and an example are available at http://www.cs.tut.fi/%7esanchesr/cellaging/ . Contact: andre.ribeiro@tut.fi Supplementary information: Supplementary data are available at Bioinformatics online.
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  • 6
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    A novel representation of genomic sequences for taxonomic clustering and visualization by means of self-organizing maps (2015)
    Oxford University Press
    Details
    Publication Date: 2015-02-27
    Description: Motivation: Self-organizing maps (SOMs) are readily available bioinformatics methods for clustering and visualizing high-dimensional data, provided that such biological information is previously transformed to fixed-size, metric-based vectors. To increase the usefulness of SOM-based approaches for the analysis of genomic sequence data, novel representation methods are required that automatically and bijectively transform aligned nucleotide sequences into numeric vectors, dealing with both nucleotide ambiguity and gaps derived from sequence alignment. Results: Six different codification variants based on Euclidean space, just like SOM processing, have been tested using two SOM models: the classical Kohonen’s SOM and growing cell structures. They have been applied to two different sets of sequences: 32 sequences of small sub-unit ribosomal RNA from organisms belonging to the three domains of life, and 44 sequences of the reverse transcriptase region of the pol gene of human immunodeficiency virus type 1 belonging to different groups and sub-types. Our results show that the most important factor affecting the accuracy of sequence clustering is the assignment of an extra weight to the presence of alignment-derived gaps. Although each of the codification variants shows a different level of taxonomic consistency, the results are in agreement with sequence-based phylogenetic reconstructions and anticipate a broad applicability of this codification method. Contact: sole@eui.upm.es Supplementary information: Supplementary data are available at Bioinformatics online.
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  • 7
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    DOMINO: development of informative molecular markers for phylogenetic and genome-wide population genetic studies in non-model organisms (2016)
    Oxford University Press
    Details
    Publication Date: 2016-08-16
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    Topics: Biology , Computer Science , Medicine
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  • 8
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    JSpeciesWS: a web server for prokaryotic species circumscription based on pairwise genome comparison (2015)
    Oxford University Press
    Details
    Publication Date: 2015-11-16
    Description: Summary: JSpecies Web Server (JSpeciesWS) is a user-friendly online service for in silico calculating the extent of identity between two genomes, a parameter routinely used in the process of polyphasic microbial species circumscription. The service measures the average nucleotide identity (ANI) based on BLAST+ (ANIb) and MUMmer (ANIm), as well as correlation indexes of tetra-nucleotide signatures (Tetra). In addition, it provides a Tetra Correlation Search function, which allows to rapidly compare selected genomes against a continuously updated reference database with currently about 32 000 published whole and draft genome sequences. For comparison, own genomes can be uploaded and references can be selected from the JSpeciesWS reference database. The service indicates whether two genomes share genomic identities above or below the species embracing thresholds, and serves as a fast way to allocate unknown genomes in the frame of the hitherto sequenced species. Availability and implementation: JSpeciesWS is available at http://jspecies.ribohost.com/jspeciesws. Supplementary information: Supplementary data are available at Bioinformatics online. Contact: mrichter@ribocon.com
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  • 9
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    OLGA: fast computation of generation probabilities of B- and T-cell receptor amino acid sequences and motifs (2019)
    Oxford University Press
    Details
    Publication Date: 2019-01-18
    Description: Motivation High-throughput sequencing of large immune repertoires has enabled the development of methods to predict the probability of generation by V(D)J recombination of T- and B-cell receptors of any specific nucleotide sequence. These generation probabilities are very non-homogeneous, ranging over 20 orders of magnitude in real repertoires. Since the function of a receptor really depends on its protein sequence, it is important to be able to predict this probability of generation at the amino acid level. However, brute-force summation over all the nucleotide sequences with the correct amino acid translation is computationally intractable. The purpose of this paper is to present a solution to this problem. Results We use dynamic programming to construct an efficient and flexible algorithm, called OLGA (Optimized Likelihood estimate of immunoGlobulin Amino-acid sequences), for calculating the probability of generating a given CDR3 amino acid sequence or motif, with or without V/J restriction, as a result of V(D)J recombination in B or T cells. We apply it to databases of epitope-specific T-cell receptors to evaluate the probability that a typical human subject will possess T cells responsive to specific disease-associated epitopes. The model prediction shows an excellent agreement with published data. We suggest that OLGA may be a useful tool to guide vaccine design. Availability and implementation Source code is available at https://github.com/zsethna/OLGA. Supplementary information Supplementary data are available at Bioinformatics online.
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  • 10
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    NGScloud: RNA-seq analysis of non-model species using cloud computing (2018)
    Oxford University Press
    Details
    Publication Date: 2018-05-03
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    Topics: Biology , Computer Science , Medicine
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