Publications by authors named "Olivier Poch"

133 Publications

Novel Approach Combining Transcriptional and Evolutionary Signatures to Identify New Multiciliation Genes.

Genes (Basel) 2021 Sep 21;12(9). Epub 2021 Sep 21.

Department of Computer Science, ICube, UMR 7357, Centre de Recherche en Biomédecine de Strasbourg, University of Strasbourg, CNRS, 67000 Strasbourg, France.

Multiciliogenesis is a complex process that allows the generation of hundreds of motile cilia on the surface of specialized cells, to create fluid flow across epithelial surfaces. Dysfunction of human multiciliated cells is associated with diseases of the brain, airway and reproductive tracts. Despite recent efforts to characterize the transcriptional events responsible for the differentiation of multiciliated cells, a lot of actors remain to be identified. In this work, we capitalize on the ever-growing quantity of high-throughput data to search for new candidate genes involved in multiciliation. After performing a large-scale screening using 10 transcriptomics datasets dedicated to multiciliation, we established a specific evolutionary signature involving Otomorpha fish to use as a criterion to select the most likely targets. Combining both approaches highlighted a list of 114 potential multiciliated candidates. We characterized these genes first by generating protein interaction networks, which showed various clusters of ciliated and multiciliated genes, and then by computing phylogenetic profiles. In the end, we selected 11 poorly characterized genes that seem like particularly promising multiciliated candidates. By combining functional and comparative genomics methods, we developed a novel type of approach to study biological processes and identify new promising candidates linked to that process.
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http://dx.doi.org/10.3390/genes12091452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8470418PMC
September 2021

A DNA Repair and Cell Cycle Gene Expression Signature in Pediatric High-Grade Gliomas: Prognostic and Therapeutic Value.

Cancers (Basel) 2021 May 7;13(9). Epub 2021 May 7.

DNA Repair and Chemoresistance, Department of Oncology, Luxembourg Institute of Health, L-1526 Luxembourg, Luxembourg.

Background: Pediatric high-grade gliomas (pHGGs) are the leading cause of mortality in pediatric neuro-oncology, displaying frequent resistance to standard therapies. Profiling DNA repair and cell cycle gene expression has recently been proposed as a strategy to classify adult glioblastomas. To improve our understanding of the DNA damage response pathways that operate in pHGGs and the vulnerabilities that these pathways might expose, we sought to identify and characterize a specific DNA repair and cell-cycle gene expression signature of pHGGs.

Methods: Transcriptomic analyses were performed to identify a DNA repair and cell-cycle gene expression signature able to discriminate pHGGs (n = 6) from low-grade gliomas (n = 10). This signature was compared to related signatures already established. We used the pHGG signature to explore already transcriptomic datasets of DIPGs and sus-tentorial pHGGs. Finally, we examined the expression of key proteins of the pHGG signature in 21 pHGG diagnostic samples and nine paired relapses. Functional inhibition of one DNA repair factor was carried out in four patients who derived H3.3 mutant cell lines.

Results: We identified a 28-gene expression signature of DNA repair and cell cycle that clustered pHGGs cohorts, in particular sus-tentorial locations, in two groups. Differential protein expression levels of PARP1 and XRCC1 were associated to mutations and amplification and linked significantly to the more radioresistant pHGGs displaying the worst outcome. Using patient-derived cell lines, we showed that the PARP-1/XRCC1 expression balance might be correlated with resistance to PARP1 inhibition.

Conclusion: We provide evidence that PARP1 overexpression, associated to XRCC1 expression, mutations, and amplification, is a new theranostic and potential therapeutic target.
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http://dx.doi.org/10.3390/cancers13092252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8125831PMC
May 2021

Potential role of the X circular code in the regulation of gene expression.

Biosystems 2021 May 7;203:104368. Epub 2021 Feb 7.

Department of Computer Science, ICube, CNRS, University of Strasbourg, Strasbourg, France. Electronic address:

The X circular code is a set of 20 trinucleotides (codons) that has been identified in the protein-coding genes of most organisms (bacteria, archaea, eukaryotes, plasmids, viruses). It has been shown previously that the X circular code has the important mathematical property of being an error-correcting code. Thus, motifs of the X circular code, i.e. a series of codons belonging to X and called X motifs, allow identification and maintenance of the reading frame in genes. X motifs are significantly enriched in protein-coding genes, but have also been identified in many transfer RNA (tRNA) genes and in important functional regions of the ribosomal RNA (rRNA), notably in the peptidyl transferase center and the decoding center. Here, we investigate the potential role of X motifs as functional elements of protein-coding genes. First, we identify the codons of the X circular code which are frequent or rare in each domain of life (archaea, bacteria, eukaryota) and show that, for the amino acids with the highest codon bias, the preferred codon is often an X codon. We also observe a correlation between the 20 X codons and the optimal codons/dicodons that have been shown to influence translation efficiency. Then, we examined recently published experimental results concerning gene expression levels in diverse organisms. The approach used is the analysis of X motifs according to their density d(X), i.e. the number of X motifs per kilobase in a gene sequence s. Surprisingly, this simple parameter identifies several unexpected relations between the X circular code and gene expression. For example, the X motifs are significantly enriched in the minimal gene set belonging to the three domains of life, and in codon-optimized genes. Furthermore, the density of X motifs generally correlates with experimental measures of translation efficiency and mRNA stability. Taken together, these results lead us to propose that the X motifs may represent a genetic signal contributing to the maintenance of the correct reading frame and the optimization and regulation of gene expression.
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http://dx.doi.org/10.1016/j.biosystems.2021.104368DOI Listing
May 2021

Dwarf planet (1) Ceres surface bluing due to high porosity resulting from sublimation.

Nat Commun 2021 01 12;12(1):274. Epub 2021 Jan 12.

University Grenoble Alpes, CNRS, Institut de Planétologie et d'Astrophysique de Grenoble (IPAG), Grenoble, 38000, France.

The Dawn mission found that the dominant colour variation on the surface of dwarf planet Ceres is a change of the visible spectral slope, where fresh impact craters are surrounded by blue (negative spectral-sloped) ejecta. The origin of this colour variation is still a mystery. Here we investigate a scenario in which an impact mixes the phyllosilicates present on the surface of Ceres with the water ice just below. In our experiment, Ceres analogue material is suspended in liquid water to create intimately mixed ice particles, which are sublimated under conditions approximating those on Ceres. The sublimation residue has a highly porous, foam-like structure made of phyllosilicates that scattered light in similar blue fashion as the Ceres surface. Our experiment provides a mechanism for the blue colour of fresh craters that can naturally emerge from the Ceres environment.
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http://dx.doi.org/10.1038/s41467-020-20494-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804090PMC
January 2021

Proteome-Scale Detection of Differential Conservation Patterns at Protein and Subprotein Levels with BLUR.

Genome Biol Evol 2021 01;13(1)

Complex Systems and Translational Bioinformatics, ICube UMR 7357, Université de Strasbourg, France.

In the multiomics era, comparative genomics studies based on gene repertoire comparison are increasingly used to investigate evolutionary histories of species, to study genotype-phenotype relations, species adaptation to various environments, or to predict gene function using phylogenetic profiling. However, comparisons of orthologs have highlighted the prevalence of sequence plasticity among species, showing the benefits of combining protein and subprotein levels of analysis to allow for a more comprehensive study of genotype/phenotype correlations. In this article, we introduce a new approach called BLUR (BLAST Unexpected Ranking), capable of detecting genotype divergence or specialization between two related clades at different levels: gain/loss of proteins but also of subprotein regions. These regions can correspond to known domains, uncharacterized regions, or even small motifs. Our method was created to allow two types of research strategies: 1) the comparison of two groups of species with no previous knowledge, with the aim of predicting phenotype differences or specializations between close species or 2) the study of specific phenotypes by comparing species that present the phenotype of interest with species that do not. We designed a website to facilitate the use of BLUR with a possibility of in-depth analysis of the results with various tools, such as functional enrichments, protein-protein interaction networks, and multiple sequence alignments. We applied our method to the study of two different biological pathways and to the comparison of several groups of close species, all with very promising results. BLUR is freely available at http://lbgi.fr/blur/.
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http://dx.doi.org/10.1093/gbe/evaa248DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851591PMC
January 2021

Understanding the causes of errors in eukaryotic protein-coding gene prediction: a case study of primate proteomes.

BMC Bioinformatics 2020 Nov 10;21(1):513. Epub 2020 Nov 10.

Department of Computer Science, ICube, CNRS, University of Strasbourg, Strasbourg, France.

Background: Recent advances in sequencing technologies have led to an explosion in the number of genomes available, but accurate genome annotation remains a major challenge. The prediction of protein-coding genes in eukaryotic genomes is especially problematic, due to their complex exon-intron structures. Even the best eukaryotic gene prediction algorithms can make serious errors that will significantly affect subsequent analyses.

Results: We first investigated the prevalence of gene prediction errors in a large set of 176,478 proteins from ten primate proteomes available in public databases. Using the well-studied human proteins as a reference, a total of 82,305 potential errors were detected, including 44,001 deletions, 27,289 insertions and 11,015 mismatched segments where part of the correct protein sequence is replaced with an alternative erroneous sequence. We then focused on the mismatched sequence errors that cause particular problems for downstream applications. A detailed characterization allowed us to identify the potential causes for the gene misprediction in approximately half (5446) of these cases. As a proof-of-concept, we also developed a simple method which allowed us to propose improved sequences for 603 primate proteins.

Conclusions: Gene prediction errors in primate proteomes affect up to 50% of the sequences. Major causes of errors include undetermined genome regions, genome sequencing or assembly issues, and limitations in the models used to represent gene exon-intron structures. Nevertheless, existing genome sequences can still be exploited to improve protein sequence quality. Perspectives of the work include the characterization of other types of gene prediction errors, as well as the development of a more comprehensive algorithm for protein sequence error correction.
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http://dx.doi.org/10.1186/s12859-020-03855-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7656754PMC
November 2020

Characterization of accessory genes in coronavirus genomes.

Virol J 2020 08 27;17(1):131. Epub 2020 Aug 27.

Laboratoire ICube, Department of Computer Science, CNRS, University of Strasbourg, F-67412, Strasbourg, France.

Background: The Covid19 infection is caused by the SARS-CoV-2 virus, a novel member of the coronavirus (CoV) family. CoV genomes code for a ORF1a / ORF1ab polyprotein and four structural proteins widely studied as major drug targets. The genomes also contain a variable number of open reading frames (ORFs) coding for accessory proteins that are not essential for virus replication, but appear to have a role in pathogenesis. The accessory proteins have been less well characterized and are difficult to predict by classical bioinformatics methods.

Methods: We propose a computational tool GOFIX to characterize potential ORFs in virus genomes. In particular, ORF coding potential is estimated by searching for enrichment in motifs of the X circular code, that is known to be over-represented in the reading frames of viral genes.

Results: We applied GOFIX to study the SARS-CoV-2 and related genomes including SARS-CoV and SARS-like viruses from bat, civet and pangolin hosts, focusing on the accessory proteins. Our analysis provides evidence supporting the presence of overlapping ORFs 7b, 9b and 9c in all the genomes and thus helps to resolve some differences in current genome annotations. In contrast, we predict that ORF3b is not functional in all genomes. Novel putative ORFs were also predicted, including a truncated form of the ORF10 previously identified in SARS-CoV-2 and a little known ORF overlapping the Spike protein in Civet-CoV and SARS-CoV.

Conclusions: Our findings contribute to characterizing sequence properties of accessory genes of SARS coronaviruses, and especially the newly acquired genes making use of overlapping reading frames.
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http://dx.doi.org/10.1186/s12985-020-01402-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7450977PMC
August 2020

MISTIC: A prediction tool to reveal disease-relevant deleterious missense variants.

PLoS One 2020 31;15(7):e0236962. Epub 2020 Jul 31.

Complex Systems and Translational Bioinformatics (CSTB), ICube laboratory - CNRS, Fédération de Médecine Translationnelle de Strasbourg (FMTS), University of Strasbourg, Strasbourg, France.

The diffusion of next-generation sequencing technologies has revolutionized research and diagnosis in the field of rare Mendelian disorders, notably via whole-exome sequencing (WES). However, one of the main issues hampering achievement of a diagnosis via WES analyses is the extended list of variants of unknown significance (VUS), mostly composed of missense variants. Hence, improved solutions are needed to address the challenges of identifying potentially deleterious variants and ranking them in a prioritized short list. We present MISTIC (MISsense deleTeriousness predICtor), a new prediction tool based on an original combination of two complementary machine learning algorithms using a soft voting system that integrates 113 missense features, ranging from multi-ethnic minor allele frequencies and evolutionary conservation, to physiochemical and biochemical properties of amino acids. Our approach also uses training sets with a wide spectrum of variant profiles, including both high-confidence positive (deleterious) and negative (benign) variants. Compared to recent state-of-the-art prediction tools in various benchmark tests and independent evaluation scenarios, MISTIC exhibits the best and most consistent performance, notably with the highest AUC value (> 0.95). Importantly, MISTIC maintains its high performance in the specific case of discriminating deleterious variants from benign variants that are rare or population-specific. In a clinical context, MISTIC drastically reduces the list of VUS (<30%) and significantly improves the ranking of "causative" deleterious variants. Pre-computed MISTIC scores for all possible human missense variants are available at http://lbgi.fr/mistic.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0236962PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7394404PMC
September 2020

A benchmark study of ab initio gene prediction methods in diverse eukaryotic organisms.

BMC Genomics 2020 Apr 9;21(1):293. Epub 2020 Apr 9.

Department of Computer Science, ICube, CNRS, University of Strasbourg, Strasbourg, France.

Background: The draft genome assemblies produced by new sequencing technologies present important challenges for automatic gene prediction pipelines, leading to less accurate gene models. New benchmark methods are needed to evaluate the accuracy of gene prediction methods in the face of incomplete genome assemblies, low genome coverage and quality, complex gene structures, or a lack of suitable sequences for evidence-based annotations.

Results: We describe the construction of a new benchmark, called G3PO (benchmark for Gene and Protein Prediction PrOgrams), designed to represent many of the typical challenges faced by current genome annotation projects. The benchmark is based on a carefully validated and curated set of real eukaryotic genes from 147 phylogenetically disperse organisms, and a number of test sets are defined to evaluate the effects of different features, including genome sequence quality, gene structure complexity, protein length, etc. We used the benchmark to perform an independent comparative analysis of the most widely used ab initio gene prediction programs and identified the main strengths and weaknesses of the programs. More importantly, we highlight a number of features that could be exploited in order to improve the accuracy of current prediction tools.

Conclusions: The experiments showed that ab initio gene structure prediction is a very challenging task, which should be further investigated. We believe that the baseline results associated with the complex gene test sets in G3PO provide useful guidelines for future studies.
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http://dx.doi.org/10.1186/s12864-020-6707-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7147072PMC
April 2020

Ammonium salts are a reservoir of nitrogen on a cometary nucleus and possibly on some asteroids.

Science 2020 03;367(6483)

Dipartimento di Matematica e Fisica "E. De Giorgi," Università del Salento, Lecce, Italy.

The measured nitrogen-to-carbon ratio in comets is lower than for the Sun, a discrepancy which could be alleviated if there is an unknown reservoir of nitrogen in comets. The nucleus of comet 67P/Churyumov-Gerasimenko exhibits an unidentified broad spectral reflectance feature around 3.2 micrometers, which is ubiquitous across its surface. On the basis of laboratory experiments, we attribute this absorption band to ammonium salts mixed with dust on the surface. The depth of the band indicates that semivolatile ammonium salts are a substantial reservoir of nitrogen in the comet, potentially dominating over refractory organic matter and more volatile species. Similar absorption features appear in the spectra of some asteroids, implying a compositional link between asteroids, comets, and the parent interstellar cloud.
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http://dx.doi.org/10.1126/science.aaw7462DOI Listing
March 2020

Novel IQCE variations confirm its role in postaxial polydactyly and cause ciliary defect phenotype in zebrafish.

Hum Mutat 2020 01 17;41(1):240-254. Epub 2019 Oct 17.

Laboratoire de Génétique médicale, UMR_S INSERM U1112, IGMA, Faculté de Médecine, FMTS, Université de Strasbourg, Strasbourg, France.

Polydactyly is one of the most frequent inherited defects of the limbs characterized by supernumerary digits and high-genetic heterogeneity. Among the many genes involved, either in isolated or syndromic forms, eight have been implicated in postaxial polydactyly (PAP). Among those, IQCE has been recently identified in a single consanguineous family. Using whole-exome sequencing in patients with uncharacterized ciliopathies, including PAP, we identified three families with biallelic pathogenic variations in IQCE. Interestingly, the c.895_904del (p.Val301Serfs*8) was found in all families without sharing a common haplotype, suggesting a recurrent mechanism. Moreover, in two families, the systemic phenotype could be explained by additional pathogenic variants in known genes (TULP1, ATP6V1B1). RNA expression analysis on patients' fibroblasts confirms that the dysfunction of IQCE leads to the dysregulation of genes associated with the hedgehog-signaling pathway, and zebrafish experiments demonstrate a full spectrum of phenotypes linked to defective cilia: Body curvature, kidney cysts, left-right asymmetry, misdirected cilia in the pronephric duct, and retinal defects. In conclusion, we identified three additional families confirming IQCE as a nonsyndromic PAP gene. Our data emphasize the importance of taking into account the complete set of variations of each individual, as each clinical presentation could finally be explained by multiple genes.
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http://dx.doi.org/10.1002/humu.23924DOI Listing
January 2020

Circular code motifs in the ribosome: a missing link in the evolution of translation?

RNA 2019 12 10;25(12):1714-1730. Epub 2019 Sep 10.

Department of Computer Science, ICube, CNRS, University of Strasbourg, Strasbourg 67000, France.

The origin of the genetic code remains enigmatic five decades after it was elucidated, although there is growing evidence that the code coevolved progressively with the ribosome. A number of primordial codes were proposed as ancestors of the modern genetic code, including comma-free codes such as the , , or codes ( = G or A, = C or T, = any nucleotide), and the circular code, an error-correcting code that also allows identification and maintenance of the reading frame. It was demonstrated previously that motifs of the circular code are significantly enriched in the protein-coding genes of most organisms, from bacteria to eukaryotes. Here, we show that imprints of this code also exist in the ribosomal RNA (rRNA). In a large-scale study involving 133 organisms representative of the three domains of life, we identified 32 universal motifs that are conserved in the rRNA of >90% of the organisms. Intriguingly, most of the universal motifs are located in rRNA regions involved in important ribosome functions, notably in the peptidyl transferase center and the decoding center that form the original "proto-ribosome." Building on the existing accretion models for ribosome evolution, we propose that error-correcting circular codes represented an important step in the emergence of the modern genetic code. Thus, circular codes would have allowed the simultaneous coding of amino acids and synchronization of the reading frame in primitive translation systems, prior to the emergence of more sophisticated start codon recognition and translation initiation mechanisms.
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http://dx.doi.org/10.1261/rna.072074.119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6859856PMC
December 2019

The Photochemistry on Space Station (PSS) Experiment: Organic Matter under Mars-like Surface UV Radiation Conditions in Low Earth Orbit.

Astrobiology 2019 08 17;19(8):1037-1052. Epub 2019 Jul 17.

1Laboratoire Interuniversitaire des Systèmes Atmosphériques (LISA), UMR CNRS 7583, Université Paris Est Créteil et Université de Paris, Institut Pierre Simon Laplace, Créteil, France.

The search for organic molecules at the surface of Mars is a top priority of the Mars Science Laboratory (NASA) and ExoMars 2020 (ESA) space missions. Their main goal is to search for past and/or present molecular compounds related to a potential prebiotic chemistry and/or a biological activity on the Red Planet. A key step to interpret their data is to characterize the preservation or the evolution of organic matter in the martian environmental conditions. Several laboratory experiments have been developed especially concerning the influence of ultraviolet (UV) radiation. However, the experimental UV sources do not perfectly reproduce the solar UV radiation reaching the surface of Mars. For this reason, the International Space Station (ISS) can be advantageously used to expose the same samples studied in the laboratory to UV radiation representative of martian conditions. Those laboratory simulations can be completed by experiments in low Earth orbit (LEO) outside the ISS. Our study was part of the Photochemistry on the Space Station experiment on board the EXPOSE-R2 facility that was kept outside the ISS from October 2014 to February 2016. Chrysene, adenine, and glycine, pure or deposited on an iron-rich amorphous mineral phase, were exposed to solar UV. The total duration of exposure to UV radiation is estimated to be in the 1250-1420 h range. Each sample was characterized prior to and after the flight by Fourier transform infrared (FTIR) spectroscopy. These measurements showed that all exposed samples were partially degraded. Their quantum efficiencies of photodecomposition were calculated in the 200-250 nm wavelength range. They range from 10 to 10 molecules·photon for pure organic samples and from 10 to 10 molecules·photon for organic samples shielded by the mineral phase. These results highlight that none of the tested organics are stable under LEO solar UV radiation conditions. The presence of an iron-rich mineral phase increases their degradation.
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http://dx.doi.org/10.1089/ast.2018.2001DOI Listing
August 2019

Bardet-Biedl syndrome: Antenatal presentation of forty-five fetuses with biallelic pathogenic variants in known Bardet-Biedl syndrome genes.

Clin Genet 2019 03;95(3):384-397

Laboratoire de Diagnostic Génétique, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.

Bardet-Biedl syndrome (BBS) is an emblematic ciliopathy associated with retinal dystrophy, obesity, postaxial polydactyly, learning disabilities, hypogonadism and renal dysfunction. Before birth, enlarged/cystic kidneys as well as polydactyly are the hallmark signs of BBS to consider in absence of familial history. However, these findings are not specific to BBS, raising the problem of differential diagnoses and prognosis. Molecular diagnosis during pregnancies remains a timely challenge for this heterogeneous disease (22 known genes). We report here the largest cohort of BBS fetuses to better characterize the antenatal presentation. Prenatal ultrasound (US) and/or autopsy data from 74 fetuses with putative BBS diagnosis were collected out of which molecular diagnosis was established in 51 cases, mainly in BBS genes (45 cases) following the classical gene distribution, but also in other ciliopathy genes (6 cases). Based on this, an updated diagnostic decision tree is proposed. No genotype/phenotype correlation could be established but postaxial polydactyly (82%) and renal cysts (78%) were the most prevalent symptoms. However, autopsy revealed polydactyly that was missed by prenatal US in 55% of the cases. Polydactyly must be carefully looked for in pregnancies with apparently isolated renal anomalies in fetuses.
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http://dx.doi.org/10.1111/cge.13500DOI Listing
March 2019

OrthoInspector 3.0: open portal for comparative genomics.

Nucleic Acids Res 2019 01;47(D1):D411-D418

Department of Computer Science, ICube, UMR 7357, University of Strasbourg, CNRS, Fédération de Médecine Translationnelle de Strasbourg, Strasbourg, France.

OrthoInspector is one of the leading software suites for orthology relations inference. In this paper, we describe a major redesign of the OrthoInspector online resource along with a significant increase in the number of species: 4753 organisms are now covered across the three domains of life, making OrthoInspector the most exhaustive orthology resource to date in terms of covered species (excluding viruses). The new website integrates original data exploration and visualization tools in an ergonomic interface. Distributions of protein orthologs are represented by heatmaps summarizing their evolutionary histories, and proteins with similar profiles can be directly accessed. Two novel tools have been implemented for comparative genomics: a phylogenetic profile search that can be used to find proteins with a specific presence-absence profile and investigate their functions and, inversely, a GO profiling tool aimed at deciphering evolutionary histories of molecular functions, processes or cell components. In addition to the re-designed website, the OrthoInspector resource now provides a REST interface for programmatic access. OrthoInspector 3.0 is available at http://lbgi.fr/orthoinspectorv3.
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http://dx.doi.org/10.1093/nar/gky1068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6323921PMC
January 2019

Evolutionary conservation and functional implications of circular code motifs in eukaryotic genomes.

Biosystems 2019 Jan 24;175:57-74. Epub 2018 Oct 24.

CSTB, ICube, CNRS, University of Strasbourg, 300 Boulevard Sébastien Brant, 67400, Illkirch, France. Electronic address:

A set X of 20 trinucleotides has been found to have the highest average occurrence in the reading frame, compared to the two shifted frames, of genes of bacteria, archaea, eukaryotes, plasmids and viruses (Michel, 2015, 2017; Arquès and Michel, 1996). This set X has an interesting mathematical property, since X is a maximal C self-complementary trinucleotide circular code (Arquès and Michel, 1996). Furthermore, any motif obtained from this circular code X has the capacity to retrieve, maintain and synchronize the reading frame in genes. In a recent study of the X motifs in the complete genome of the yeast, Saccharomyces cerevisiae, it was shown that they are significantly enriched in the reading frame of the genes (protein-coding regions) of the genome (Michel et al., 2017). It was suggested that these X motifs may be evolutionary relics of a primitive code originally used for gene translation. The aim of this paper is to address two questions: are X motifs conserved during evolution? and do they continue to play a functional role in the processes of genome decoding and protein production? In a large scale analysis involving complete genomes from four mammals and nine different yeast species, we highlight specific evolutionary pressures on the X motifs in the genes of all the genomes, and identify important new properties of X motif conservation at the level of the encoded amino acids. We then compare the occurrence of X motifs with existing experimental data concerning protein expression and protein production, and report a significant correlation between the number of X motifs in a gene and increased protein abundance. In a general way, this work suggests that motifs from circular codes, i.e. motifs having the property of reading frame retrieval, may represent functional elements located within the coding regions of extant genomes.
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http://dx.doi.org/10.1016/j.biosystems.2018.10.014DOI Listing
January 2019

PROBE: analysis and visualization of protein block-level evolution.

Bioinformatics 2018 10;34(19):3390-3392

Department of Computer Science, ICube, UMR 7357, University of Strasbourg, CNRS, Fédération de Médecine Translationnelle de Strasbourg, Strasbourg, France.

Summary: Comparative studies of protein sequences are widely used in evolutionary and comparative genomics studies, but there is a lack of efficient tools to identify conserved regions ab initio within a protein multiple alignment. PROBE provides a fully automatic analysis of protein family conservation, to identify conserved regions, or 'blocks', that may correspond to structural/functional domains or motifs. Conserved blocks are identified at two different levels: (i) family level blocks indicate sites that are probably of central importance to the protein's structure or function, and (ii) sub-family level blocks highlight regions that may signify functional specialization, such as binding partners, etc. All conserved blocks are mapped onto a phylogenetic tree and can also be visualized in the context of the multiple sequence alignment. PROBE thus facilitates in-depth studies of sequence-structure-function-evolution relationships, and opens the way to block-level phylogenetic profiling.

Availability And Implementation: Freely available on the web at http://www.lbgi.fr/∼julie/probe/web.
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http://dx.doi.org/10.1093/bioinformatics/bty367DOI Listing
October 2018

Enrichment of Circular Code Motifs in the Genes of the Yeast Saccharomyces cerevisiae.

Life (Basel) 2017 Dec 3;7(4). Epub 2017 Dec 3.

Complex Systems and Translational Bioinformatics, ICube, University of Strasbourg, CNRS, 300 Boulevard Sébastien Brant, 67400 Illkirch, France.

A set X of 20 trinucleotides has been found to have the highest average occurrence in the reading frame, compared to the two shifted frames, of genes of bacteria, archaea, eukaryotes, plasmids and viruses. This set X has an interesting mathematical property, since X is a maximal C3 self-complementary trinucleotide circular code. Furthermore, any motif obtained from this circular code X has the capacity to retrieve, maintain and synchronize the original (reading) frame. Since 1996, the theory of circular codes in genes has mainly been developed by analysing the properties of the 20 trinucleotides of X, using combinatorics and statistical approaches. For the first time, we test this theory by analysing the X motifs, i.e., motifs from the circular code X, in the complete genome of the yeast . Several properties of X motifs are identified by basic statistics (at the frequency level), and evaluated by comparison to R motifs, i.e., random motifs generated from 30 different random codes R. We first show that the frequency of X motifs is significantly greater than that of R motifs in the genome of . We then verify that no significant difference is observed between the frequencies of X and R motifs in the non-coding regions of , but that the occurrence number of X motifs is significantly higher than R motifs in the genes (protein-coding regions). This property is true for all cardinalities of X motifs (from 4 to 20) and for all 16 chromosomes. We further investigate the distribution of X motifs in the three frames of genes and show that they occur more frequently in the reading frame, regardless of their cardinality or their length. Finally, the ratio of X genes, i.e., genes with at least one X motif, to non-X genes, in the set of verified genes is significantly different to that observed in the set of putative or dubious genes with no experimental evidence. These results, taken together, represent the first evidence for a significant enrichment of X motifs in the genes of an extant organism. They raise two hypotheses: the X motifs may be evolutionary relics of the primitive codes used for translation, or they may continue to play a functional role in the complex processes of genome decoding and protein synthesis.
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http://dx.doi.org/10.3390/life7040052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5745565PMC
December 2017

MyGeneFriends: A Social Network Linking Genes, Genetic Diseases, and Researchers.

J Med Internet Res 2017 06 16;19(6):e212. Epub 2017 Jun 16.

ICUBE UMR 7357, Complex Systems and Translational Bioinformatics, Université de Strasbourg - CNRS - FMTS, Strasbourg, France.

Background: The constant and massive increase of biological data offers unprecedented opportunities to decipher the function and evolution of genes and their roles in human diseases. However, the multiplicity of sources and flow of data mean that efficient access to useful information and knowledge production has become a major challenge. This challenge can be addressed by taking inspiration from Web 2.0 and particularly social networks, which are at the forefront of big data exploration and human-data interaction.

Objective: MyGeneFriends is a Web platform inspired by social networks, devoted to genetic disease analysis, and organized around three types of proactive agents: genes, humans, and genetic diseases. The aim of this study was to improve exploration and exploitation of biological, postgenomic era big data.

Methods: MyGeneFriends leverages conventions popularized by top social networks (Facebook, LinkedIn, etc), such as networks of friends, profile pages, friendship recommendations, affinity scores, news feeds, content recommendation, and data visualization.

Results: MyGeneFriends provides simple and intuitive interactions with data through evaluation and visualization of connections (friendships) between genes, humans, and diseases. The platform suggests new friends and publications and allows agents to follow the activity of their friends. It dynamically personalizes information depending on the user's specific interests and provides an efficient way to share information with collaborators. Furthermore, the user's behavior itself generates new information that constitutes an added value integrated in the network, which can be used to discover new connections between biological agents.

Conclusions: We have developed MyGeneFriends, a Web platform leveraging conventions from popular social networks to redefine the relationship between humans and biological big data and improve human processing of biomedical data. MyGeneFriends is available at lbgi.fr/mygenefriends.
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http://dx.doi.org/10.2196/jmir.6676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5493784PMC
June 2017

MiSynPat: An integrated knowledge base linking clinical, genetic, and structural data for disease-causing mutations in human mitochondrial aminoacyl-tRNA synthetases.

Hum Mutat 2017 10 27;38(10):1316-1324. Epub 2017 Jun 27.

Université de Strasbourg, CNRS, Architecture et Réactivité de l'ARN, Strasbourg, France.

Numerous mutations in each of the mitochondrial aminoacyl-tRNA synthetases (aaRSs) have been implicated in human diseases. The mutations are autosomal and recessive and lead mainly to neurological disorders, although with pleiotropic effects. The processes and interactions that drive the etiology of the disorders associated with mitochondrial aaRSs (mt-aaRSs) are far from understood. The complexity of the clinical, genetic, and structural data requires concerted, interdisciplinary efforts to understand the molecular biology of these disorders. Toward this goal, we designed MiSynPat, a comprehensive knowledge base together with an ergonomic Web server designed to organize and access all pertinent information (sequences, multiple sequence alignments, structures, disease descriptions, mutation characteristics, original literature) on the disease-linked human mt-aaRSs. With MiSynPat, a user can also evaluate the impact of a possible mutation on sequence-conservation-structure in order to foster the links between basic and clinical researchers and to facilitate future diagnosis. The proposed integrated view, coupled with research on disease-related mt-aaRSs, will help to reveal new functions for these enzymes and to open new vistas in the molecular biology of the cell. The purpose of MiSynPat, freely available at http://misynpat.org, is to constitute a reference and a converging resource for scientists and clinicians.
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http://dx.doi.org/10.1002/humu.23277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5638098PMC
October 2017

Insights into Ciliary Genes and Evolution from Multi-Level Phylogenetic Profiling.

Mol Biol Evol 2017 08;34(8):2016-2034

Complex Systems and Translational Bioinformatics, ICube UMR 7357, Université de Strasbourg, Fédération de Médecine Translationnelle, Strasbourg, France.

Cilia (flagella) are important eukaryotic organelles, present in the Last Eukaryotic Common Ancestor, and are involved in cell motility and integration of extracellular signals. Ciliary dysfunction causes a class of genetic diseases, known as ciliopathies, however current knowledge of the underlying mechanisms is still limited and a better characterization of genes is needed. As cilia have been lost independently several times during evolution and they are subject to important functional variation between species, ciliary genes can be investigated through comparative genomics. We performed phylogenetic profiling by predicting orthologs of human protein-coding genes in 100 eukaryotic species. The analysis integrated three independent methods to predict a consensus set of 274 ciliary genes, including 87 new promising candidates. A fine-grained analysis of the phylogenetic profiles allowed a partitioning of ciliary genes into modules with distinct evolutionary histories and ciliary functions (assembly, movement, centriole, etc.) and thus propagation of potential annotations to previously undocumented genes. The cilia/basal body localization was experimentally confirmed for five of these previously unannotated proteins (LRRC23, LRRC34, TEX9, WDR27, and BIVM), validating the relevance of our approach. Furthermore, our multi-level analysis sheds light on the core gene sets retained in gamete-only flagellates or Ecdysozoa for instance. By combining gene-centric and species-oriented analyses, this work reveals new ciliary and ciliopathy gene candidates and provides clues about the evolution of ciliary processes in the eukaryotic domain. Additionally, the positive and negative reference gene sets and the phylogenetic profile of human genes constructed during this study can be exploited in future work.
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http://dx.doi.org/10.1093/molbev/msx146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5850483PMC
August 2017

Remote Sensing of Potential Biosignatures from Rocky, Liquid, or Icy (Exo)Planetary Surfaces.

Astrobiology 2017 03 10;17(3):231-252. Epub 2017 Mar 10.

4 Physikalisches Institut, Universität Bern , Bern, Switzerland .

To detect signs of life by remote sensing on objects of our Solar System and on exoplanets, the characterization of light scattered by surface life material could complement possible clues given by the atmospheric composition. We reviewed the reflectance spectra of a broad selection of major biomolecules that constitute terrestrial carbon-based life from 0.4 to 2.4 μm, and we discuss their detectability through atmospheric spectral windows. Biomolecule features in the near-infrared (0.8-2.4 μm) will likely be obscured by water spectral features and some atmospheric gases. The visible range (0.4-0.8 μm), including the strong spectral features of pigments, is the most favorable. We investigated the detectability of a pigmented microorganism (Deinococcus radiodurans) when mixed with silica sand, liquid water, and water-ice particles representative of diverse surfaces of potentially habitable worlds. We measured the visible to near-infrared reflectance spectra (0.4-2.4 μm) and the visible phase curves (at 0.45 and 0.75 μm) of the mixtures to assess how the surface medium and the viewing geometry affect the detectability of the microorganisms. The results show that ice appears to be the most favorable medium for the detection of pigments. Water ice is bright and featureless from 0.4 to 0.8 μm, allowing the absorption of any pigment present in the ice to be well noticeable. We found that the visible phase curve of water ice is the most strongly affected by the presence of pigments, with variations of the spectral slope by more than a factor of 3 with phase angles. Finally, we show that the sublimation of the ice results in the concentration of the biological material onto the surface and the consequent increase of its signal. These results have applications to the search for life on icy worlds, such as Europa or Enceladus. Key Words: Remote sensing-Biosignatures-Reflectance spectroscopy-Exoplanets-Spectroscopic biosignatures-Pigments. Astrobiology 17, 231-252.
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http://dx.doi.org/10.1089/ast.2016.1523DOI Listing
March 2017

Identification and Characterization of MicroRNA Differentially Expressed in Macrophages Exposed to Porphyromonas gingivalis Infection.

Infect Immun 2017 03 23;85(3). Epub 2017 Feb 23.

Department of Pharmacology, NYMC, Touro College and University System, Valhalla, New York, USA

MicroRNAs (miRNAs) are short, noncoding RNAs involved in the regulation of several processes associated with inflammatory diseases and infection. Bacterial infection modulates miRNA expression to subvert any innate immune response. In this study we analyzed, using microarray analysis, the bacterial modulation of miRNAs in bone marrow-derived macrophages (BMMs) in which activity was induced by infection with The expression of several miRNAs was modulated 3 h postinfection (at a multiplicity of infection of 25). A bioinformatic analysis was performed to further identify pathways related to the innate immune host response under the influence of selected miRNAs. To assess the effects of the miRNAs identified on cytokine secretion (tumor necrosis factor alpha [TNF-α] and interleukin-10 [IL-10]), BMMs were transfected with selected miRNA mimics and inhibitors. Transfection with mmu-miR-155 and mmu-miR-2137 did not modify TNF-α secretion, while their inhibitors increased it. Inhibitors of mmu-miR-2137 and mmu-miR-7674 increased the secretion of the anti-inflammatory factor IL-10. In -infected BMMs, mmu-miR-155-5p significantly decreased TNF-α secretion while inhibitor of mmu-miR-2137 increased IL-10 secretion. , in a mouse model of -induced calvarial bone resorption, injection of mmu-miR-155-5p or anti-mmu-miR-2137 reduced the size of the lesion significantly. Furthermore, anti-mmu-miR-2137 significantly reduced inflammatory cell infiltration, osteoclast activity, and bone loss. Bioinformatic analysis demonstrated that pathways related to cytokine- and chemokine-related pathways but also osteoclast differentiation may be involved in the effects observed. This study contributes further to our understanding of -induced modulation of miRNAs and their physiological effects. It highlights the potential therapeutic merits of targeting mmu-miR-155-5p and mmu-miR-2137 to control inflammation induced by infection.
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http://dx.doi.org/10.1128/IAI.00771-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5328478PMC
March 2017

Identification of a Novel Homozygous Nonsense Mutation Confirms the Implication of GNAT1 in Rod-Cone Dystrophy.

PLoS One 2016 15;11(12):e0168271. Epub 2016 Dec 15.

Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut de la Vision, Paris, France.

GNAT1, encoding the transducin subunit Gα, is an important element of the phototransduction cascade. Mutations in this gene have been associated with autosomal dominant and autosomal recessive congenital stationary night blindness. Recently, a homozygous truncating GNAT1 mutation was identified in a patient with late-onset rod-cone dystrophy. After exclusion of mutations in genes underlying progressive inherited retinal disorders, by targeted next generation sequencing, a 32 year-old male sporadic case with severe rod-cone dystrophy and his unaffected parents were investigated by whole exome sequencing. This led to the identification of a homozygous nonsense variant, c.963C>A p.(Cys321*) in GNAT1, which was confirmed by Sanger sequencing. The mother was heterozygous for this variant whereas the variant was absent in the father. c.963C>A p.(Cys321*) is predicted to produce a shorter protein that lacks critical sites for the phototransduction cascade. Our work confirms that the phenotype and the mode of inheritance associated with GNAT1 variants can vary from autosomal dominant, autosomal recessive congenital stationary night blindness to autosomal recessive rod-cone dystrophy.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0168271PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5158031PMC
July 2017

LEON-BIS: multiple alignment evaluation of sequence neighbours using a Bayesian inference system.

BMC Bioinformatics 2016 Jul 7;17(1):271. Epub 2016 Jul 7.

Department of Computer Science, ICube, UMR 7357, University of Strasbourg, CNRS, Fédération de médecine translationnelle de Strasbourg, Strasbourg, France.

Background: A standard procedure in many areas of bioinformatics is to use a multiple sequence alignment (MSA) as the basis for various types of homology-based inference. Applications include 3D structure modelling, protein functional annotation, prediction of molecular interactions, etc. These applications, however sophisticated, are generally highly sensitive to the alignment used, and neglecting non-homologous or uncertain regions in the alignment can lead to significant bias in the subsequent inferences.

Results: Here, we present a new method, LEON-BIS, which uses a robust Bayesian framework to estimate the homologous relations between sequences in a protein multiple alignment. Sequences are clustered into sub-families and relations are predicted at different levels, including 'core blocks', 'regions' and full-length proteins. The accuracy and reliability of the predictions are demonstrated in large-scale comparisons using well annotated alignment databases, where the homologous sequence segments are detected with very high sensitivity and specificity.

Conclusions: LEON-BIS uses robust Bayesian statistics to distinguish the portions of multiple sequence alignments that are conserved either across the whole family or within subfamilies. LEON-BIS should thus be useful for automatic, high-throughput genome annotations, 2D/3D structure predictions, protein-protein interaction predictions etc.
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http://dx.doi.org/10.1186/s12859-016-1146-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4936259PMC
July 2016

Identification of an Alternative Splicing Product of the Otx2 Gene Expressed in the Neural Retina and Retinal Pigmented Epithelial Cells.

PLoS One 2016 17;11(3):e0150758. Epub 2016 Mar 17.

INSERM, U968, Paris, F-75012, France.

To investigate the complexity of alternative splicing in the retina, we sequenced and analyzed a total of 115,706 clones from normalized cDNA libraries from mouse neural retina (66,217) and rat retinal pigmented epithelium (49,489). Based upon clustering the cDNAs and mapping them with their respective genomes, the estimated numbers of genes were 9,134 for the mouse neural retina and 12,050 for the rat retinal pigmented epithelium libraries. This unique collection of retinal of messenger RNAs is maintained and accessible through a web-base server to the whole community of retinal biologists for further functional characterization. The analysis revealed 3,248 and 3,202 alternative splice events for mouse neural retina and rat retinal pigmented epithelium, respectively. We focused on transcription factors involved in vision. Among the six candidates suitable for functional analysis, we selected Otx2S, a novel variant of the Otx2 gene with a deletion within the homeodomain sequence. Otx2S is expressed in both the neural retina and retinal pigmented epithelium, and encodes a protein that is targeted to the nucleus. OTX2S exerts transdominant activity on the tyrosinase promoter when tested in the physiological environment of primary RPE cells. By overexpressing OTX2S in primary RPE cells using an adeno associated viral vector, we identified 10 genes whose expression is positively regulated by OTX2S. We find that OTX2S is able to bind to the chromatin at the promoter of the retinal dehydrogenase 10 (RDH10) gene.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0150758PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4795653PMC
August 2016

Ubiquitin Receptor Protein UBASH3B Drives Aurora B Recruitment to Mitotic Microtubules.

Dev Cell 2016 Jan;36(1):63-78

Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Centre National de la Recherche Scientifique UMR 7104, Institut National de la Santé et de la Recherche Médicale U964, Université de Strasbourg, 67404 Illkirch, France. Electronic address:

Mitosis ensures equal segregation of the genome and is controlled by a variety of ubiquitylation signals on substrate proteins. However, it remains unexplored how the versatile ubiquitin code is read out during mitotic progression. Here, we identify the ubiquitin receptor protein UBASH3B as an important regulator of mitosis. UBASH3B interacts with ubiquitylated Aurora B, one of the main kinases regulating chromosome segregation, and controls its subcellular localization but not protein levels. UBASH3B is a limiting factor in this pathway and is sufficient to localize Aurora B to microtubules prior to anaphase. Importantly, targeting Aurora B to microtubules by UBASH3B is necessary for the timing and fidelity of chromosome segregation in human cells. Our findings uncover an important mechanism defining how ubiquitin attachment to a substrate protein is decoded during mitosis.
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http://dx.doi.org/10.1016/j.devcel.2015.12.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5400057PMC
January 2016

Tex19 and Sectm1 concordant molecular phylogenies support co-evolution of both eutherian-specific genes.

BMC Evol Biol 2015 Oct 12;15:222. Epub 2015 Oct 12.

Primordial Germ Cells' Ontogeny and Pluripotency Laboratory, Functional Genomics and Cancer Department, Genetics Institute of Molecular and Cellular Biology (IGBMC), INSERM U964/CNRS UMR 1704/Université de Strasbourg, 1 rue Laurent Fries, 67404, Illkirch, France.

Background: Transposable elements (TE) have attracted much attention since they shape the genome and contribute to species evolution. Organisms have evolved mechanisms to control TE activity. Testis expressed 19 (Tex19) represses TE expression in mouse testis and placenta. In the human and mouse genomes, Tex19 and Secreted and transmembrane 1 (Sectm1) are neighbors but are not homologs. Sectm1 is involved in immunity and its molecular phylogeny is unknown.

Methods: Using multiple alignments of complete protein sequences (MACS), we inferred Tex19 and Sectm1 molecular phylogenies. Protein conserved regions were identified and folds were predicted. Finally, expression patterns were studied across tissues and species using RNA-seq public data and RT-PCR.

Results: We present 2 high quality alignments of 58 Tex19 and 58 Sectm1 protein sequences from 48 organisms. First, both genes are eutherian-specific, i.e., exclusively present in mammals except monotremes (platypus) and marsupials. Second, Tex19 and Sectm1 have both duplicated in Sciurognathi and Bovidae while they have remained as single copy genes in all further placental mammals. Phylogenetic concordance between both genes was significant (p-value < 0.05) and supported co-evolution and functional relationship. At the protein level, Tex19 exhibits 3 conserved regions and 4 invariant cysteines. In particular, a CXXC motif is present in the N-terminal conserved region. Sectm1 exhibits 2 invariant cysteines and an Ig-like domain. Strikingly, Tex19 C-terminal conserved region was lost in Haplorrhini primates while a Sectm1 C-terminal extra domain was acquired. Finally, we have determined that Tex19 and Sectm1 expression levels anti-correlate across the testis of several primates (ρ = -0.72) which supports anti-regulation.

Conclusions: Tex19 and Sectm1 co-evolution and anti-regulated expressions support a strong functional relationship between both genes. Since Tex19 operates a control on TE and Sectm1 plays a role in immunity, Tex19 might suppress an immune response directed against cells that show TE activity in eutherian reproductive tissues.
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http://dx.doi.org/10.1186/s12862-015-0506-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4603632PMC
October 2015

Effect of nontronite smectite clay on the chemical evolution of several organic molecules under simulated martian surface ultraviolet radiation conditions.

Astrobiology 2015 Mar 3;15(3):221-37. Epub 2015 Mar 3.

1 LISA, Universités Paris Est Créteil and Paris Diderot , Institut Pierre Simon Laplace, UMR CNRS 7583, Créteil, France .

Most of the phyllosilicates detected at the surface of Mars today are probably remnants of ancient environments that sustained long-term bodies of liquid water at the surface or subsurface and were possibly favorable for the emergence of life. Consequently, phyllosilicates have become the main mineral target in the search for organics on Mars. But are phyllosilicates efficient at preserving organic molecules under current environmental conditions at the surface of Mars? We monitored the qualitative and quantitative evolutions of glycine, urea, and adenine in interaction with the Fe(3+)-smectite clay nontronite, one of the most abundant phyllosilicates present at the surface of Mars, under simulated martian surface ultraviolet light (190-400 nm), mean temperature (218 ± 2 K), and pressure (6 ± 1 mbar) in a laboratory simulation setup. We tested organic-rich samples that were representative of the evaporation of a small, warm pond of liquid water containing a high concentration of organics. For each molecule, we observed how the nontronite influences its quantum efficiency of photodecomposition and the nature of its solid evolution products. The results reveal a pronounced photoprotective effect of nontronite on the evolution of glycine and adenine; their efficiencies of photodecomposition were reduced by a factor of 5 when mixed at a concentration of 2.6 × 10(-2) mol of molecules per gram of nontronite. Moreover, when the amount of nontronite in the sample of glycine was increased by a factor of 2, the gain of photoprotection was multiplied by a factor of 5. This indicates that the photoprotection provided by the nontronite is not a purely mechanical shielding effect but is also due to stabilizing interactions. No new evolution product was firmly identified, but the results obtained with urea suggest a particular reactivity in the presence of nontronite, leading to an increase of its dissociation rate.
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http://dx.doi.org/10.1089/ast.2014.1230DOI Listing
March 2015

Integrated annotation and analysis of in situ hybridization images using the ImAnno system: application to the ear and sensory organs of the fetal mouse.

PLoS One 2015 23;10(2):e0118024. Epub 2015 Feb 23.

LBGI Bioinformatique et Génomique Intégratives, ICube Laboratory and Strasbourg Federation of Translational Medecine (FMTS), University of Strasbourg and CNRS, Strasbourg, France.

An in situ hybridization (ISH) study was performed on 2000 murine genes representing around 10% of the protein-coding genes present in the mouse genome using data generated by the EURExpress consortium. This study was carried out in 25 tissues of late gestation embryos (E14.5), with a special emphasis on the developing ear and on five distinct developing sensory organs, including the cochlea, the vestibular receptors, the sensory retina, the olfactory organ, and the vibrissae follicles. The results obtained from an analysis of more than 11,000 micrographs have been integrated in a newly developed knowledgebase, called ImAnno. In addition to managing the multilevel micrograph annotations performed by human experts, ImAnno provides public access to various integrated databases and tools. Thus, it facilitates the analysis of complex ISH gene expression patterns, as well as functional annotation and interaction of gene sets. It also provides direct links to human pathways and diseases. Hierarchical clustering of expression patterns in the 25 tissues revealed three main branches corresponding to tissues with common functions and/or embryonic origins. To illustrate the integrative power of ImAnno, we explored the expression, function and disease traits of the sensory epithelia of the five presumptive sensory organs. The study identified 623 genes (out of 2000) concomitantly expressed in the five embryonic epithelia, among which many (∼12%) were involved in human disorders. Finally, various multilevel interaction networks were characterized, highlighting differential functional enrichments of directly or indirectly interacting genes. These analyses exemplify an under-represention of "sensory" functions in the sensory gene set suggests that E14.5 is a pivotal stage between the developmental stage and the functional phase that will be fully reached only after birth.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0118024PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338146PMC
January 2016
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