Miguel A. Andrade‐Navarro

Johannes Gutenberg University Mainz

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Papers

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i-10 index

Research Trends

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Document Type

Co-Authors

Pablo Mier

Johannes Gutenberg University Mainz

Jean−Fred Fontaine

Johannes Gutenberg University Mainz

Enrique M. Muro

Johannes Gutenberg University Mainz

Carolina Perez‐Iratxeta

Ottawa Hospital

Gregorio Alanis‐Lobato

Boehringer Ingelheim (Germany)

Peer Bork

European Molecular Biology Laboratory

Nancy Mah

Fraunhofer Institute for Biomedical Engineering

Steffen Albrecht

University of Auckland

Jonas Ibn-Salem

University Medical Center of the Johannes Gutenberg University Mainz

Maximilian Sprang

Johannes Gutenberg University Mainz

Cooperative Institutions

Johannes Gutenberg University Mainz

155

Max Delbrück Center

150

Heidelberg University

126

Charité - Universitätsmedizin Berlin

100

University Medical Center of the Johannes Gutenberg University Mainz

German Cancer Research Center

Freie Universität Berlin

Centre National de la Recherche Scientifique

Humboldt-Universität zu Berlin

Institute of Molecular Biology

Author Statistics

Papers

Citation

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Research Field

Nuclear inclusions of pathogenic ataxin-1 induce oxidative stress and perturb the protein synthesis machinery

Redox Biology (2020)

Stamatia Laidou Gregorio Alanis‐Lobato Jan Přibyl Tamás Raskó Boris Tichý

Spinocerebellar ataxia type-1 (SCA1) is caused by an abnormally expanded polyglutamine (polyQ) tract in ataxin-1. These expansions are responsible for protein misfolding and self-assembly into intranuclear inclusion bodies (IIBs) that are somehow linked to neuronal death. However, owing to lack of a suitable cellular model, the downstream consequences of IIB formation are yet to be resolved. Here, we describe a nuclear protein aggregation model of pathogenic human ataxin-1 and characterize IIB effects. Using an inducible Sleeping Beauty transposon system, we overexpressed the ATXN1(Q82) gene in human mesenchymal stem cells that are resistant to the early cytotoxic effects caused by the expression of the mutant protein. We characterized the structure and the protein composition of insoluble polyQ IIBs which gradually occupy the nuclei and are responsible for the generation of reactive oxygen species. In response to their formation, our transcriptome analysis reveals a cerebellum-specific perturbed protein interaction network, primarily affecting protein synthesis. We propose that insoluble polyQ IIBs cause oxidative and nucleolar stress and affect the assembly of the ribosome by capturing or down-regulating essential components. The inducible cell system can be utilized to decipher the cellular consequences of polyQ protein aggregation. Our strategy provides a broadly applicable methodology for studying polyQ diseases.

Proteostasis

Inclusion bodies

10.1016/j.redox.2020.101458

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Citations (16)

Alkemio: association of chemicals with biomedical topics by text and data mining

Nucleic Acids Research (2014)

José A. Gijón-Correas Miguel A. Andrade‐Navarro Jean−Fred Fontaine

The PubMed® database of biomedical citations allows the retrieval of scientific articles studying the function of chemicals in biology and medicine. Mining millions of available citations to search reported associations between chemicals and topics of interest would require substantial human time. We have implemented the Alkemio text mining web tool and SOAP web service to help in this task. The tool uses biomedical articles discussing chemicals (including drugs), predicts their relatedness to the query topic with a naïve Bayesian classifier and ranks all chemicals by P-values computed from random simulations. Benchmarks on seven human pathways showed good retrieval performance (areas under the receiver operating characteristic curves ranged from 73.6 to 94.5%). Comparison with existing tools to retrieve chemicals associated to eight diseases showed the higher precision and recall of Alkemio when considering the top 10 candidate chemicals. Alkemio is a high performing web tool ranking chemicals for any biomedical topics and it is free to non-commercial users. Availability: http://cbdm.mdc-berlin.de/∼medlineranker/cms/alkemio.

10.1093/nar/gku432

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Citations (16)

A protocol for the update of references to scientific literature in biological databases.

PubMed (2003)

Carolina Perez‐Iratxeta Nagore Astola Francesca D. Ciccarelli Parantu K. Sha Peer Bork

Relevance

Benchmark (surveying)

Biological database

Scientific literature

Source

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Citations (5)

Glutamine Codon Usage and polyQ Evolution in Primates Depend on the Q Stretch Length

Genome Biology and Evolution (2018)

Pablo Mier Miguel A. Andrade‐Navarro

Amino acid usage in a proteome depends mostly on its taxonomy, as it does the codon usage in transcriptomes. Here, we explore the level of variation in the codon usage of a specific amino acid, glutamine, in relation to the number of consecutive glutamine residues. We show that CAG triplets are consistently more abundant in short glutamine homorepeats (polyQ, four to eight residues) than in shorter glutamine stretches (one to three residues), leading to the evolutionary growth of the repeat region in a CAG-dependent manner. The length of orthologous polyQ regions is mostly stable in primates, particularly the short ones. Interestingly, given a short polyQ the CAG usage is higher in unstable-in-length orthologous polyQ regions. This indicates that CAG triplets produce the necessary instability for a glutamine stretch to grow. Proteins related to polyQ-associated diseases behave in a more extreme way, with longer glutamine stretches in human and evolutionarily closer nonhuman primates, and an overall higher CAG usage. In the light of our results, we suggest an evolutionary model to explain the glutamine codon usage in polyQ regions.

Stop codon

10.1093/gbe/evy046

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Citations (18)

FASTA Herder: a web application to trim protein sequence sets

ScienceOpen Research (2014)

Caroline Louis‐Jeune Miguel A. Andrade‐Navarro Carol Perez‐Iratxeta

The ever increasing number of sequences in protein databases usually turns out large numbers of homologs in sequence similarity searches. While information from homology can be very useful for functional prediction based on amino acid conservation, many of these homologs usually have high levels of identity among themselves, which hinders multiple sequence alignment (MSA) computation and, especially, visualization. More generally, high redundancy reduces the usability of a protein set in machine learning applications and biases statistical analyses. We developed an algorithm to identify redundant sequence homologs that can be culled producing a streamlined FASTA file. As a difference from other automatic approaches that only aggregate sequences with high identity, our method clusters near-full length homologs allowing for lower sequence identity thresholds. Our method was fully tested and implemented in a web application called FASTA Herder, publicly available at http://www.ogic.ca/projects/fh/orain.html .

Sequence (biology)

Protein sequencing

Homology

10.14293/s2199-1006.1.sor-life.a67837.v1

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Citations (0)

Tandem repeats lead to sequence assembly errors and impose multi-level challenges for genome and protein databases

Nucleic Acids Research (2019)

Ole K. Tørresen Bastiaan Star Pablo Mier Miguel A. Andrade‐Navarro Alex Bateman

Abstract The widespread occurrence of repetitive stretches of DNA in genomes of organisms across the tree of life imposes fundamental challenges for sequencing, genome assembly, and automated annotation of genes and proteins. This multi-level problem can lead to errors in genome and protein databases that are often not recognized or acknowledged. As a consequence, end users working with sequences with repetitive regions are faced with ‘ready-to-use’ deposited data whose trustworthiness is difficult to determine, let alone to quantify. Here, we provide a review of the problems associated with tandem repeat sequences that originate from different stages during the sequencing-assembly-annotation-deposition workflow, and that may proliferate in public database repositories affecting all downstream analyses. As a case study, we provide examples of the Atlantic cod genome, whose sequencing and assembly were hindered by a particularly high prevalence of tandem repeats. We complement this case study with examples from other species, where mis-annotations and sequencing errors have propagated into protein databases. With this review, we aim to raise the awareness level within the community of database users, and alert scientists working in the underlying workflow of database creation that the data they omit or improperly assemble may well contain important biological information valuable to others.

Sequence assembly

10.1093/nar/gkz841

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Citations (274)

Integration of Expressed Sequence Tag Data Flanking Predicted RNA Secondary Structures Facilitates Novel Non-Coding RNA Discovery

PLoS ONE (2011)

Paul M. Krzyzanowski Feodor D. Price Enrique M. Muro Michael A. Rudnicki Miguel A. Andrade‐Navarro

Many computational methods have been used to predict novel non-coding RNAs (ncRNAs), but none, to our knowledge, have explicitly investigated the impact of integrating existing cDNA-based Expressed Sequence Tag (EST) data that flank structural RNA predictions. To determine whether flanking EST data can assist in microRNA (miRNA) prediction, we identified genomic sites encoding putative miRNAs by combining functional RNA predictions with flanking ESTs data in a model consistent with miRNAs undergoing cleavage during maturation. In both human and mouse genomes, we observed that the inclusion of flanking ESTs adjacent to and not overlapping predicted miRNAs significantly improved the performance of various methods of miRNA prediction, including direct high-throughput sequencing of small RNA libraries. We analyzed the expression of hundreds of miRNAs predicted to be expressed during myogenic differentiation using a customized microarray and identified several known and predicted myogenic miRNA hairpins. Our results indicate that integrating ESTs flanking structural RNA predictions improves the quality of cleaved miRNA predictions and suggest that this strategy can be used to predict other non-coding RNAs undergoing cleavage during maturation.

Coding region

10.1371/journal.pone.0020561

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Citations (7)

Additional file 2 of seqQscorer: automated quality control of next-generation sequencing data using machine learning

Figshare (2021)

Steffen Albrecht Maximilian Sprang Miguel A. Andrade‐Navarro Jean−Fred Fontaine

Additional file 2. Table of grid search parameters. Parameters are relevant to a scikit-learn implementation.

10.6084/m9.figshare.14173803

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Citations (0)

Oct4 Targets Regulatory Nodes to Modulate Stem Cell

Function A. Campbell Carolina Perez‐Iratxeta Miguel A. Andrade‐Navarro Michael A. Rudnicki

Summary of Oct4 Correlated Genes with Probeset ID,gene symbol, gene name, direction and percentage of correlation,chromosomal location, summary GO category used for Figure 2and GO biological process were listed when known.Found at: doi:10.1371/journal.pone.0000553.s002 (0.28 MBXLS) Table S3 GoStat AnalysisFound at: doi:10.1371/journal.pone.0000553.s003 (0.33 MBXLS) Table S4 Oct4/Sox2 putative binding site analysis with Genesymbol, RefSeq or Ensembl ID, putative binding sequence, andlocation in transcript enumeratedFound at: doi:10.1371/journal.pone.0000553.s004 (0.11 MBXLS) Table S5 Primer sequences for Oct4 target validation by ChIP/QRT-PCRFound at: doi:10.1371/journal.pone.0000553.s005 (0.06 MBDOC) Table S6 Annotation of Oct4 targets.Found at: doi:10.1371/journal.pone.0000553.s006 (0.09 MBDOC) ACKNOWLEDGMENTS The Authors would like to acknowledge the Stem Cell Network for theirsupport of the Stem Cell Genomics Project and the technical staff of theOntario Genomics Innovation Centre for their expert assistance. Kindthanks to Dave Picketts, Marjorie Brand, and Jeff Dilworth for insightfuldiscussions. MAR is an International Scholar of the Howard HughesMedical Institute and holds the Canada Research Chair in MolecularGenetics.

RefSeq

Ensembl

Table (database)

UniGene

Source

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Citations (0)

Reading the Evolution of Compartmentalization in the Ribosome Assembly Toolbox: The YRG Protein Family

PLoS ONE (2017)

Pablo Mier Antonio J. Pérez‐Pulido Emmanuel G. Reynaud Miguel A. Andrade‐Navarro

Reconstructing the transition from a single compartment bacterium to a highly compartmentalized eukaryotic cell is one of the most studied problems of evolutionary cell biology. However, timing and details of the establishment of compartmentalization are unclear and difficult to assess. Here, we propose the use of molecular markers specific to cellular compartments to set up a framework to advance the understanding of this complex intracellular process. Specifically, we use a protein family related to ribosome biogenesis, YRG (YlqF related GTPases), whose evolution is linked to the establishment of cellular compartments, leveraging the current genomic data. We analyzed orthologous proteins of the YRG family in a set of 171 proteomes for a total of 370 proteins. We identified ten YRG protein subfamilies that can be associated to six subcellular compartments (nuclear bodies, nucleolus, nucleus, cytosol, mitochondria, and chloroplast), and which were found in archaeal, bacterial and eukaryotic proteomes. Our analysis reveals organism streamlining related events in specific taxonomic groups such as Fungi. We conclude that the YRG family could be used as a compartmentalization marker, which could help to trace the evolutionary path relating cellular compartments with ribosome biogenesis.

Compartmentalization (fire protection)

Proteome

ribosome biogenesis

Cellular compartment

Proteostasis

Ran

Protein family

Compartment (ship)

Organelle biogenesis

10.1371/journal.pone.0169750

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Citations (8)