Claude Pasquier | Université Nice Sophia Antipolis (original) (raw)

Papers by Claude Pasquier

Cancers

Glioblastomas (GBs) are incurable brain tumors. The persistence of aggressive stem-like tumor cel... more Glioblastomas (GBs) are incurable brain tumors. The persistence of aggressive stem-like tumor cells after cytotoxic treatments compromises therapeutic efficacy, leading to GBM recurrence. Forcing the GBM cells to irreversibly abandon their aggressive stem-like phenotype may offer an alternative to conventional cytotoxic treatments. Here, we show that the RNA binding protein CELF2 is strongly expressed in mitotic and OLIG2-positive GBM cells, while it is downregulated in differentiated and non-mitotic cells by miR-199a-3p, exemplifying GBM intra-tumor heterogeneity. Using patient-derived cells and human GBM samples, we demonstrate that CELF2 plays a key role in maintaining the proliferative/OLIG2 cell phenotype with clonal and tumorigenic properties. Indeed, we show that CELF2 deficiency in patient-derived GSCs drastically reduced tumor growth in the brains of nude mice. We further show that CELF2 promotes TRIM28 and G9a expression, which drive a H3K9me3 epigenetic profile responsibl...

HAL (Le Centre pour la Communication Scientifique Directe), Apr 13, 2020

The role of the RNAi/Dicer/Ago system in degrading RNA viruses has been elusive in mammals in the... more The role of the RNAi/Dicer/Ago system in degrading RNA viruses has been elusive in mammals in the past, which has prompted authors to think that interferon (IFN) synthesis is essential in this clade, relegating the RNAi defense strategy against viral infection as an accessory function. However, recent publications highlight the existence of abundant viral small interference and micro RNAs (VsiRNAs and VmiRNAs) in both cell-line and whole organism based experiments, indicating a contribution of these molecules in host responses and/or viral replication. We explore the theoretical possibility that RNAi triggered by SARS-CoV-2 might degrade some host transcripts in the opposite direction, although this hypothesis seems counterintuitive. The SARS-CoV-2 genome was therefore computationally searched for exact intrapairing within the viral RNA and exact hybrid pairing with the human transcriptome over a minimum of 20 bases in length. Minimal segments of 20-base lengths of SARS-CoV-2 RNA were found based on the theoretical matching with existing complementary strands in the human host transcriptome. Few human genes potentially annealing with SARS-CoV-2 RNA, including mitochondrial deubiquitinase USP30, the subunit of ubiquitin protein ligase complex FBXO21 and two long noncoding RNAs, were retrieved. The hypothesis that viral-originated RNAi might mediate degradation of host transcriptome messages was corroborated by published high throughput sequencing of RNA from infected tissues and cultured cells, clinical observation and phylogenetic comparative analysis, indicating a strong specificity of these SARS-CoV-2 hybrid pairing sequences for human genomes.

International Journal of Molecular Sciences, Nov 20, 2022

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

HAL (Le Centre pour la Communication Scientifique Directe), Apr 1, 2009

During the last decade, several clustering and association rule mining techniques have been appli... more During the last decade, several clustering and association rule mining techniques have been applied to highlight groups of coregulated genes in gene expression data. Nowadays, integrating these data and biological knowledge into a single framework has become a major challenge to improve the relevance of mined patterns and simplify their interpretation by biologists. GenMiner was developed for mining association rules from such integrated datasets. It combines a new nomalized discretization method, called NorDi, and the JClose algorithm to extract condensed representations for association rules. Experimental results show that GenMiner requires less memory than Apriori based approaches and that it improves the relevance of extracted rules. Moreover, association rules obtained revealed significant co-annotated and co-expressed gene patterns showing important biological relationships supported by recent biological literature.

Heliyon, Jun 1, 2021

International Journal of Molecular Sciences

The phosphorylation of proteins affects their functions in extensively documented circumstances. ... more The phosphorylation of proteins affects their functions in extensively documented circumstances. However, the role of phosphorylation in many interactive networks of proteins remains very elusive due to the experimental limits of exploring the transient interaction in a large complex of assembled proteins induced by stimulation. Previous studies have suggested that phosphorylation is a recent evolutionary process that differently regulates ortholog proteins in numerous lineages of living organisms to create new functions. Despite the fact that numerous phospho-proteins have been compared between species, little is known about the organization of the full phospho-proteome, the role of phosphorylation to orchestrate large interactive networks of proteins, and the intertwined phospho-landscape in these networks. In this report, we aimed to investigate the acquired role of phosphate addition in the phenomenon of protein networking in different orders of living organisms. Our data highli...

HAL (Le Centre pour la Communication Scientifique Directe), Jan 29, 2013

Biology has become an enormously data-rich subject. Data is generated in many flavors and follows... more Biology has become an enormously data-rich subject. Data is generated in many flavors and follows particularities of the omics perspective adopted along experimental studies. For instance, genomics is the field of study dealing with genomes and it is mostly associated with the static view (the genes and where they are placed along the genome). The dynamic view is brought from the transcriptomics perspective, so the gene expression and its regulation. Finally, interactomics is usually associated to gene products, proteins, and their interactions. However it could also be seen as a huge graph network with layers of interaction integrating distinct omics perspectives. Omics science applications of unsupervised and/or supervised machine learning (ML) techniques abound in the literature. In this tutorial, we discuss machine learning on omics data, putting the emphasis on (i) mapping and (ii) learning omics patterns. We consider three main omics data: genomics, transcriptomics and interac...

G3 (Bethesda, Md.), Jul 17, 2017

Double-stranded DNA is able to form triple-helical structures by accommodating a third nucleotide... more Double-stranded DNA is able to form triple-helical structures by accommodating a third nucleotide strand. A nucleic acid triplex occurs according to Hoogsteen rules that predict the stability and affinity of the third strand bound to the Watson-Crick duplex. The "triplex-forming oligonucleotide" (TFO) can be a short sequence of RNA that binds to the major groove of the targeted duplex only when this duplex presents a sequence of purine or pyrimidine bases in one of the DNA strands. Many nuclear proteins are known to bind triplex DNA or DNA:RNA, but their biological functions are unexplored. We identified sequences that are capable of engaging as the "triplex-forming oligonucleotide" in both the pre-lncRNA and pre-mRNA collections of Drosophila melanogaster These motifs were matched against the Drosophila genome in order to identify putative sequences of triplex formation in intergenic regions, promoters and introns/exons. Most of the identified TFOs appear to be ...

Pharmaceutics

Despite the development of new therapeutic strategies, cancer remains one of the leading causes o... more Despite the development of new therapeutic strategies, cancer remains one of the leading causes of mortality worldwide. One of the current major challenges is the resistance of cancers to chemotherapy treatments inducing metastases and relapse of the tumor. The Hedgehog receptor Patched (Ptch1) is overexpressed in many types of cancers. We showed that Ptch1 contributes to the efflux of doxorubicin and plays an important role in the resistance to chemotherapy in adrenocortical carcinoma (ACC), a rare cancer which presents strong resistance to the standard of care chemotherapy treatment. In the present study, we isolated and characterized a subpopulation of the ACC cell line H295R in which Ptch1 is overexpressed and more present at the cell surface. This cell subpopulation is more resistant to doxorubicin, grows as spheroids, and has a greater capability of clonogenicity, migration, and invasion than the parental cells. Xenograft experiments performed in mice and in ovo showed that th...

Life Science Alliance, 2021

In this study, we reanalyzed available datasets of gene expression changes in female Drosophila h... more In this study, we reanalyzed available datasets of gene expression changes in female Drosophila head induced by mating. Mated females present metabolic phenotypic changes and display behavioral characteristics that are not observed in virgin females, such as repulsion to male sexual aggressiveness, fidelity to food spots selected for oviposition, and restriction to the colonization of new niches. We characterize gene networks that play a role in female brain plasticity after mating using AMINE, a novel algorithm to find dysregulated modules of interacting genes. The uncovered networks of altered genes revealed a strong specificity for each successive period of life span after mating in the female head, with little conservation between them. This finding highlights a temporal order of recruitment of waves of interconnected genes which are apparently transiently modified: the first wave disappears before the emergence of the second wave in a reversible manner and ends with few consoli...

HAL is a multi-disciplinary open access archive for the deposit and dissemination of sci-entific ... more HAL is a multi-disciplinary open access archive for the deposit and dissemination of sci-entific research documents, whether they are pub-lished or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L’archive ouverte pluridisciplinaire HAL, est destinée au dépôt et a ̀ la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d’enseignement et de recherche français ou étrangers, des laboratoires publics ou privés. Journal of Integrative Bioinformatics 2006

Computational Biology and Chemistry, 2020

Perfect annealing between microRNAs (miRNAs) and messenger RNAs (mRNAs) was computationally searc... more Perfect annealing between microRNAs (miRNAs) and messenger RNAs (mRNAs) was computationally searched at a broad scale in the human genome to determine whether theoretical pairing is restrictively represented in functional subnetworks or is randomly distributed. Massive RNA interference (RNAi) pairing motifs in genes constitute a remarkable subnetwork that displays highly genetically and biochemically interconnected genes. These analyses show unexpected repertoires of genes defined by their congruence in comatching with miRNAs at numerous sites and by their interconnection based on protein/protein interactions or proteins regulating the activity of others. This offers insights into the putatively coregulated homeostasis of large networks of genes by RNAi, whereas other networks seem to be independent of this regulatory mode. Genes accordingly defined by theoretical RNAi pairing cluster mainly in subnetworks related to cellular, metabolic and developmental processes and their regulation. Indeed, genes harboring numerous potential sites of hybridization with miRNAs are highly enriched with GO terms depicting the abovementioned processes and are grouped in a subnetwork of genes that are significantly more highly connected than they would be according to a random distribution. The significant number of interacting genes that present numerous potential comatches with miRNAs suggests that they may be under the control of the integrative and concerted action of multiple miRNAs.

Within multi-domain sentiment analysis, we study how different domain-dependent polarities can be... more Within multi-domain sentiment analysis, we study how different domain-dependent polarities can be learned for the same concepts. To this aim, we extend an existing approach based on the propagation of fuzzy polarities over a semantic graph capturing background linguistic knowledge to learn concept polarities with respect to various domains and their uncertainty from labeled datasets. In particular, we use POS tagging to refine the association between terms and concepts and word embedding to enhance the construction of the semantic graph. The proposed approach is then evaluated on a standard benchmark, showing that the combined use of POS tagging and word embedding improves its performance. One particularly strong point of the proposed approach is its recall, which is always very close to 100%. In addition, we observe that it exhibits good cross-domain generalization capabilities.

Proceedings of the Tenth International Conference on Computational Systems-Biology and Bioinformatics, 2019

The identification of condition specific gene sets from transcriptomic experiments has important ... more The identification of condition specific gene sets from transcriptomic experiments has important biological applications, ranging from the discovery of altered pathways between different phenotypes to the selection of disease-related biomarkers. Statistical approaches using only gene expression data are based on an overly simplistic assumption that the genes with the most altered expressions are the most important in the process under study. However, a phenotype is rarely a direct consequence of the activity of a single gene, but rather reflects the interplay of several genes to perform certain molecular processes. Many methods have been proposed to analyze gene activity in the light of our knowledge about their molecular interactions. We propose, in this article, a populationbased meta-heuristics based on new crossover and mutation operators. Our method achieves state of the art performance in an independent simulation experiment used in other studies. Applied to a public transcriptomic dataset of patients afflicted with Hepatocellular carcinoma, our method was able to identify significant modules of genes with meaningful biological relevance. CCS CONCEPTS • Theory of computation → Evolutionary algorithms; • Applied computing → Computational transcriptomics; Biological networks.

The identification of condition-specific gene sets from transcriptomic experiments is important t... more The identification of condition-specific gene sets from transcriptomic experiments is important to reveal regulatory and signaling mechanisms associated with a given cellular response. Statistical approaches using only expression data allow the identification of genes whose expression is most altered between different conditions. However, a phenotype is rarely a direct consequence of the activity of a single gene, but rather reflects the interplay of several genes to carry out certain molecular processes. Many methods have been proposed to analyze the activity of genes in light of our knowledge of their molecular interactions. However, existing methods have many limitations that make them of limited use to biologists: they detect modules that are too large, too small, or they require the users to specify a priori the size of the modules they are looking for.We propose AMINE (Active Module Identification through Network Embedding), an efficient method for the identification of active...

The role of the RNAi/Dicer/Ago system to degrade RNA viruses has been elusive in mammals, which p... more The role of the RNAi/Dicer/Ago system to degrade RNA viruses has been elusive in mammals, which prompted authors to think that interferon (IFN) synthesis is essential in this clade relegating the RNAi defense strategy against viral infection as accessory function. We explore the theoretical possibilities that RNAi triggered by SARS-CoV-2 might degrade some host transcripts in the opposite direction although this hypothesis seems counter intuitive. SARS-CoV-2 genome was therefore computational searched for exact intra pairing within the viral RNA and also hybrid exact pairing with human transcriptome over a minimum 20 bases length. Minimal segments of 20 bases length of SARS-CoV-2 RNA were found based on the theoretical matching with existing complementary strands in the human host transcriptome. Few human genes potentially annealing with SARS-CoV-2 RNA, among them mitochondrial deubiquitinase USP30, a subunit of ubiquitin protein ligase complex FBXO21 along with two long coding RNAs...

Scientific Reports, 2017

MicroRNAs, small non-coding elements implied in gene regulation, are very interesting biomarkers ... more MicroRNAs, small non-coding elements implied in gene regulation, are very interesting biomarkers for various diseases such as cancers. They represent potential prodigious biotechnologies for early diagnosis and gene therapies. However, experimental verification of microRNA-disease associations are time-consuming and costly, so that computational modeling is a proper solution. Previously, we designed MiRAI, a predictive method based on distributional semantics, to identify new associations between microRNA molecules and human diseases. Our preliminary results showed very good prediction scores compared to other available methods. However, MiRAI performances depend on numerous parameters that cannot be tuned manually. In this study, a parallel evolutionary algorithm is proposed for finding an optimal configuration of our predictive method. The automatically parametrized version of MiRAI achieved excellent performance. It highlighted new miRNA-disease associations, especially the potential implication of mir-188 and mir-795 in various diseases. In addition, our method allowed to detect several putative false associations contained in the reference database.

Knowledge and Information Systems, 2016

Attributed directed graphs are directed graphs in which nodes are associated with sets of attribu... more Attributed directed graphs are directed graphs in which nodes are associated with sets of attributes. Many data from the real world can be naturally represented by this type of structure, but few algorithms are able to directly handle these complex graphs. Mining attributed graphs is a difficult task because it requires combining the exploration of the graph structure with the identification of frequent itemsets. In addition, due to the combinatorics on itemsets, subgraph isomorphisms (which have a significant impact on performances) are much more numerous than in labeled graphs. In this paper, we present a new data mining method that can extract frequent patterns from one or more directed attributed graphs. We show how to reduce the combinatorial explosion induced by subgraph isomorphisms thanks to an appropriate processing of automorphic patterns.

Knowledge and Information Systems, 2015

Frequent pattern mining is an important data mining task with a broad range of applications. Init... more Frequent pattern mining is an important data mining task with a broad range of applications. Initially focused on the discovery of frequent itemsets, studies were extended to mine structural forms like sequences, trees or graphs. In this paper, we introduce a new domain of patterns, attributed trees (atrees), and a method to extract these patterns in a forest of atrees. Attributed trees are trees in which vertices are associated with itemsets. Mining this type of patterns (called asubtrees), which combines tree mining and itemset mining, requires the exploration of a huge search space. To make our approach scalable, we investigate the mining of condensed representations. For attributed trees, the classical concept of closure involves both itemset closure and structural closure. We present three algorithms for mining all patterns, closed patterns w.r.t. itemsets (content) and/or structure in attributed trees. We show that, for low support values, mining content-closed attributed trees is a good compromise between non-redundancy of solutions and execution time.