Hub members Have many expertise, covering most of the fields in bioinformatics and biostatistics. You'll find below a non-exhaustive list of these expertise

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Searched keyword : RNA-seq

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Marie-Agnès DILLIES

Group : HEAD - Hub Core

I obtained an engineering degree in Biomedical engineering from Université de Technologie de Compiègne (UTC) in 1989, a master degree in Control of Complex Systems from UTC in 1990, a PhD in Control of Complex Systems from UTC in 1993, a University Degree in Human Genetics from The University of Rennes 1 in 2001 and a master degree in Functional Genomics from University Paris Diderot (Paris 7) in 2002. I worked as a statistician at the Transcriptome and Epigenome Platform from 2002 to 2017, where I was responsible for the statistical analyses of the data and had an important training activity (on the campus and outside). Since 2015 I have been co-head of the Bioinformatics and Biostatistics Hub within the Center of Bioinformatics, Biostatistics and Integrative Biology (C3BI). I am co-director of the Pasteur course Introduction to Data Analysis and co-organiser of the sincellTE summer school (a school dedicated to single cell transcriptome and epigenome data analysis). I am also co-managing the StatOmique group which gathers more than 60 statisticians from France.

RNA-seqStatistical inferenceTranscriptomicsBiostatisticsApplication of mathematics in sciencesExploratory data analysisIllumina HiSeqStatistical experiment designSequencing

Projects (4)


Group : DETACHED - Detached : Labex milieu intérieur

After graduating from Paris VI University with a PhD in Genetics on the “Role of histone protein post-translational modifications in splicing regulation” that I performed in the Epigenetic Regulation unit at the Institut Pasteur, I carried out two post-doctoral experiences. I first worked for three years as a postdoctoral associate of the Whitehead Institute for Biomedical Research/MIT in Cambridge (USA). My main project consisted in the integration of genomic and epigenomic data in order to predict the transcription factors that are potentially at the core of the regulation of the cell-type specific gene expression programs. I then joined the Institut Curie where I deepened my experience in multi-omics data analyses and integration to identify non-coding RNAs involved in cancer progression. I have recently joined the HUB-C3BI of the Institut Pasteur where I am performing high-throughput data integration to better understand biological complexity and contribute to precision medicine development.

ATAC-seqChIP-seqEpigenomicsNon coding RNAPathway AnalysisRNA-seqSingle CellSystems BiologyTool DevelopmentTranscriptomicsData integrationGraph theory and analysisCell biology and developmental biology
Projects (1)

Related projects (30)

Mise a disposition d'un(e) bioinformaticien(ne) du hub pour les analyses bioinformatiques du transcriptome et de l epigenome

La PF Transcriptome et Epigenome développe des projets de séquençage à haut débit (collaboration et service) avec des équipes du Campus. Ceux-ci couvrent l'ensemble des thématiques du campus ainsi qu'une large gamme d'organismes (des virus aux mammifères). La plate-forme exerce des activités de biologie humide (construction des librairies et séquençage) et de biologie sèche (analyse bioinformatiques et statistiques). La personne mise a disposition interagira étroitement avec les autres bioinformaticiens du pôle BioMics et du Hub. Ses activités concerneront notamment: - La participation à la conception et à la mise en place des projets avec les équipes demandeuses, la prise en charge des analyses et le reporting aux utilisateurs - La mise en place d'un workflow d'analyse bioinformatique des données de transcriptome /épigénome en étroite collaboration avec le C3BI, la DSI et les autres bioinformaticiens du pole. Ce workflow permettra le contrôle qualité des données, leur prétraitement, le mapping des séquences sur les génomes/transcriptomes de réference, et le comptage des reads pour les différents éléments de l'annotation - L'adaptation du workflow d'analyse aux questions biologiques et aux organismes étudiés dans le cadre des activités de la PF - L'activité de veille technologique et bibliographique (test et validation de nouveaux outils d'analyse, updates d'outils existants...) - La mise en place et le développement d'outils d'analyse adaptés aux futurs projets de la PF: single cell RNAseq, métatranscriptome, ChIPseq, analyse des isoformes de splicing.. Ceci se fera notamment via la réalisation d'analyses dédiées avec certains utilisateurs. Les outils mis en place et validés dans ce cadre seront ensuite utilisés pour l'ensemble des projets. - L'activité de communication et de formation (participation aux réunions du consortium France Génomique,formation permanente à l' Institut Pasteur… - la participation a d autres projets du Pole BioMics (selon disponibilité) Bernd Jagla, qui était le bioinformaticien de la plateforme a rejoint le Hub au 1er janvier 2016. Rachel Legendre est mise a disposition depuis le 2 novembre 2015 et remplace Bernd Jagla. Je souhaite que Rachel Legendre soit mise à disposition de la plateforme pour une durée d'au moins 2 ans.

Project status : In Progress

A long-term mission for an assigned CIH-embedded bioinformatician to provide bioinformatic support to the CIH community

The Center for Human Immunology (CIH) supports researchers involved in translational research projects by providing access to 16 different cutting edge technologies. Currently, the CIH hosts over 60 scientific projects coming from 8 departments of the Institut Pastuer and 5 external teams. In order to respond to the growing needs of these projects in the area of single cell analysis, the CIH has introduced a significant number of single-cell/single-molecule technologies over the past 2-3 years. These new technologies, such as the Personal Genome Machine (PGM) and Ion Proton sequencers, iSCAN microarray scanner, Nanostring technology for transcriptomics profiling and real-time PCR machine BioMark, give rise to large datasets with high dimensionality. Such trend, in terms of data complexity, is also true for flow cytometry technologies (currently reaching over 20 parameters per cell). The exploration of this data is generally beyond the scope of scientists involved in translational research projects. In order to maximize the research outcomes obtained from the analysis of these rich datasets, and to ensure that the full potential of our technologies can be served to the users of the CIH, we would require a proximity bioinformatics support. A CIH-embedded bioinformatician would: 1) design and implement standard analysis pipelines for each of the data-rich technologies of the CIH; 2) provide regular ‘bioinformatics clinics’ to allow scientists the possibility to customize standard pipelines to their specific needs; 3) run trainings on the ‘R software’ platform and other data analysis tools (such as Qlucore) of interest for the CIH users. The objective would be to empower the users to run exploratory analysis by themselves, and to teach good practices in terms of data management and data analysis.    

Project status : In Progress

Nanotherapeutics for multidrug-resistant tuberculosis

Tuberculosis (TB) still remains a major public health problem with estimated 9 million incident cases and 1.5 million deaths in 2014 (WHO, Global Tuberculosis Report 2015). More worrisome is the emergence of multi drug resistance (MDR), or even extensively resistant (XDR) M. tuberculosis strains worldwide. The standardized treatment of pan-susceptible tuberculosis is the administration of two antibiotics (rifampicin and isoniazid) for six months, accompanied by two additional antibiotics (pyrazinamid and ethambutol) for the first two months. Although very efficacious, this treatment is very demanding due to the duration and the possible side effects. The treatment of MDR-TB is less standardized, with more toxic and poorly tolerated drugs, resulting in lower cure rates. Therefore, we need not only more molecules with antimycobacterial activity, but also, we urgently need new strategies to increase our therapeutic arsenal for treating MDR-TB. Only three new drugs, bedaquiline, delamanid and PA-824 have been tested in phase2/3 clinical trials.

In this context, the european funded project NAREB has been created. It brings together 14 partners from 8 EU Member and Associated States, and it aims to (i) screen different combinations of antibiotic drugs with nano-carriers (lipid, polymeric, biopolymeric) with and without targeting ligands, (ii) coload antibiotics in order to develop innovative therapeutic combination therapies (iii) test in vitro and in vivo the best therapeutic combinations. In particular, we will analyze more in-depth the effect of bedaquilin, new TB drugs and nano-carriers on the host/bacterial transcriptome using RNAseq.

Project status : Awaiting Publication

Identification of Tac4 mRNA targets

We are interested in the cytoplasmic quality control of gene expression and more especially into the behavior of aberrant peptides which could be generated from non-conform translation events. We are now investigating the role of a Saccharomyces cerevisiae RNA helicase protein that we named Tac4 (for Translation associated Component 4). We showed that this protein is involved in translation. We demonstrated, by sucrose gradient and affinity purification that Tac4 interacts with the ribosome. A first UV cross-linking and cDNA analysis (CRAC) experiment clearly revealed that Tac4 interacts with the 18S rRNA of the 40S ribosomal subunit and we precisely defined the crosslink point. These preliminary results also suggested an enrichment of the 3’-end regions of mRNAs. This implies that Tac4 could not only interact with the small ribosomal subunit but also directly with mRNA. Tac4 is conserved through the evolution and its mammalian homologue is involved in initiation of translation. Therefore, we thought that Tac4 could be associated with the 5’-end rather than with the 3’-end. However, a recent paper from the Rachel Green’s lab showed that translation reinitiation into the 3’-UTR region may occurs when translation termination is affected (Young et al., Cell 2015). The factors and molecular mechanisms implicated in these events are not known. Altogether, our preliminary results suggest that Tac4 is an excellent candidate participating to the unwinding of RNA structure or to the release of some RNA-binding proteins into the 3’-end mRNA. We now would like to 1) confirm that Tac4 preferentially interacts with the 3’-end of mRNA, 2) determine whether Tac4 interacts with a region upstream the Stop codon or in the 3’-UTR of the mRNA, 3) identify the mRNA targets to determine whether Tac4 could have a general role in translation or could only be involved in translation of some specific mRNA.

Project status : In Progress

Study of the early pathogenesis during Lassa fever in cynomolgus monkeys and its correlation with the outcome

Because of their increasing incidence, dramatic severity, lack of treatment or vaccine, complicated diagnosis, misreading of the pathogenesis, and need for a maximum containment, Viral Hemorrhagic Fevers (VHF) constitute a major public health problem. There is therefore an urgent need to further study VHF to understand the pathogenesis of the severe disease and the host responses involved in their control or in the dramatic damages. Among VHF, Lassa fever (LF) is probably the most worrying one because of its endemicity and the large number of cases. LF is caused by the Old-World arenavirus Lassa virus (LASV). It is endemic to West Africa and is responsible for 300,000 cases and 5,000 to 6,000 deaths each year. We propose here to study the pathogenesis of VHF by using LF in cynomolgus monkeys as a paradigm, with a particular emphasis on the very early events. The viral tropism, pathophysiological mechanisms, and immune responses will be studied during the course of infection, including the incubation period. Powerful approaches will be used to (1) identify early biological markers of infection, to be able to confirm infection and isolate patients; (2) determine the viral tropism and dynamics during the course of infection to understand the natural history of virus into its host. (3) characterize the early pathogenic events that lead to the severe hemorrhagic syndrome to fully understand the pathophysiogenesis of VHF and identify new therapeutic targets. (4) identify the immune responses involved in the control of infection or in the fatal outcome, to reveal the involvement of immunopathological mechanisms and help to design a vaccine approach. This ambitious and unprecedented project will allow to develop therapeutic and prophylactic approaches but also to identify early biological markers of infection and improve the early diagnosis to optimize the management of outbreaks in the field and increase the survival rate in patients.

Project status : In Progress

Characterization of a Salmonella mutant carrying a single amino-acid substitution in the stress sigma factor RpoS

Project status : Closed

Identification of Ago2-bound nuclear transcripts and genomic loci in adult zebrafish neural stem cells

Adult neurogenesis is the process by which adult neural stem cells (NSCs) produce new neuronal and glial cells throughout an animal life. Studies in vertebrates have unveiled the crucial importance of this phenomenon for neural tissue homeostasis and proper brain function. Fundamentally, this process is a balance between maintaining a quiescent NSC pool and recruiting them into the neurogenesis cascade. Using the adult zebrafish anterior brain (telencephalon) as a model, we aim at deciphering the molecular mechanisms governing this balance. We identified a microRNA, miR-9, as a prominent quiescence enforcer. Unexpectedly, miR-9 concentrates into the nucleus of quiescent adult NSCs, together with Argonaute proteins (notably Ago2), effector proteins of microRNAs. This nuclear enrichment of Ago/miR-9 is not observed in embryonic or juvenile fish, being thus a signature of deep adult NSC quiescence. It is also observed in mouse NSCs. We wish to use nuclear miR-9/Ago2 as molecular entry points into the molecular mechanisms controlling this adult-specific deep NSC quiescence state. Within this frame, the present project aims to identify Ago2-bound nuclear targets. Through fractionation experiments, we could detect Ago proteins both in the nuclear soluble and in the chromatin-associated fractions of adult zebrafish NSCs. Thus, we built genetic tools to recover the nuclear Ago2-bound transcripts and genomic loci, ie. using CLIP-seq and DamID approaches, respectively. The enriched transcript sequences will be screened for potential miRNA-binding motifs. Putative genomic targets will be screened, in addition, for specific motifs and for their coincidence with defined functional regions (eg. coding or regulatory). The data will be cross-matched with the transcriptome and proteome of miR-9-positive versus –negative adult NSCs. Together, these data should help elaborate hypotheses on the molecular mode(s) of action of nuclear miR-9/AgAgo2 when controlling adult NSC quiescence.

Project status : Pending