Integrated and spatial-temporal multiscale modeling of liver guide in vivo experiments in healthy & chronic disease states: a blue print for systems medicine?

EVENT : C3BI Seminars


Main speaker : Dirk Drasdo, from INRIA / IZBI Joint Research Group Date : 20-09-2018 at 02:00 pm Location : Salle Retrovirus – Bâtiment LWOFF ,Institut Pasteur, Paris


Background and Aims:  Hyperammonemia after drug-induced peri-central liver lobule damage, as from overdosing acetaminophen (paracetamol), and can lead to encephalopathy and dead of the patient. Guided by mathematical models, the consensus set of chemical reactions for detoxification of liver from ammonia has recently been shown to fail in explaining ammonia-detoxification after drug-induced peri-central damage (Schliess et. al., 2014). Our aim is to demonstrate how integrated and spatial-temporal models mimicking detoxification of the blood from ammonia in virtual tissue samples can assist in guiding identification of missing molecular mechanisms, or predicting the impact of micro-architectural alterations due to acute or chronic damage on ammonia detoxification. Our modeling methodology is very general.     Method:The consensus and alternative detoxification mechanisms have been implemented within mathematical integrated and spatial-temporal multi-scale models to test various hypotheses on potentially missing mechanisms in ammonia detoxification during liver regeneration after drug-induced pericentral damage in silicoin a virtual liver lobule (Drasdo et. al., J. Hepat. 2014). The multi-scale model simulates blood flow and molecular transport in the spatial lobule micro-architecture and displays each individual hepatocyte in space and time. Detoxification reactions are executed in each virtual hepatocyte. This makes in silicotesting of hypothesized mechanisms feasible from the molecular up to the tissue scale. The results are directly compared to experiments in mouse. Finally, fibrotic streets have been added to the model to predict the possible impact of architectural distortions and micro-shunts.     Results:We demonstrate how multiscale and multilevel models guided experiments towards identification of a previously unrecognized ammonia detoxification mechanism, that has the potential of improving treatment in hyperammonemia (Ghallab et. al., J. Hepat. 2016). The same model predicts for CCl4-induced fibrosis a reduced detoxification capacity for ammonia. Finally we outline how the whole body scale can be included to arrive at a model spanning molecular up to whole body scale permitting to study the relation of molecular changes and micro-architecture on whole body blood circulation, and briefly summarize results of integration of APAP toxic pathway as HGF signaling.    

Conclusion:Refined multi-scale models increasingly permit realistic prediction of liver function as well as of toxic injury in acute and chronic damage states. Those models can integrate data from various sources, in vitro, different animal models or human data. The direct representation of liver micro-architecture in those models will open up the future perspective to feed these models with patient-specific data, hence generating a virtual twin of a patients’ liver to guide personalized diagnosis and therapy planning.


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Signatures of ecological processes in microbial community time series

EVENT : C3BI Seminars


Main speaker : Karoline Faust, from KU Leuven Date : 04-10-2018 at 02:00 pm Location : Auditorium Francois Jacob – BIME (26) ,Institut Pasteur, Paris


Nowadays, a number of densely sampled microbial community time series is available, where the abundance of community members is tracked over several months through sequencing. These data allow exploring community dynamics by investigating signatures of underlying ecological processes that are present in the community time series. In this seminar, I will present our work on the exploitation of time series properties to distinguish between different ecological processes behind the observed dynamics

  http://psbweb05.psb.ugent.be/conet/karoline/

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Nucleotide-level analysis of genetic variation in the bacterial pan-genome

EVENT : C3BI Seminars


Main speaker : Zamin Iqbal, from Royal Society/Wellcome Trust Sir Henry Dale Fellow, EMBL-EBI Date : 07-03-2019 at 02:00 pm Location : Auditorium Francois Jacob – BIME (26) ,Institut Pasteur, Paris


When we study evolution of a species, we use different models, depending on what we want to achieve or infer. We might restrict to SNP variation in the “core genome”  (presumably inherited vertically) to study phylogeography or to study an outbreak. In reducing the problem to the analysis of SNPs (and invariant sites), it has been possible for researchers to build a range of sophisticated phylogenetic models. However once we try to incorporate genome organisation, chromosomal rearrangements, movement of plasmids, transposons or phage, then the modelling problem is far harder. The question of how to  properly model bacterial genetic variation is wide open and extremely challenging.
A prerequisite for any solution to this, is a decision on how to describe the variation in the first place – you cannot model variation until you represent it. Note that this is true even if you have perfect genome assemblies: even if it were possible to multiple sequence align them, this would not really help with how to notice that a SNP at one position in one genome is “the same” as a SNP somewhere else in another.
In this talk,  I want to discuss a solution we have been developing to this representation problem. We show how it is possible to represent the pan genome of a species as a network of “floating” graphs, representing the ensemble of known variation in  pathology blocks (we use genes and intergenic regions, but this could be done for mobile elements also). In doing so it becomes possible to discover and describe genetic variation at fine (SNP/indel) and coarse (gene order) level.
This is a major research theme for my group and I describe progress to date, including results on both illumina and nanopore data.

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C3BI Courses: Introduction to Molecular Phylogenetics – Hong Kong 2018

General Information:

This introductory course aims to give the basic theoretical and practical concepts, best practices, and software necessary to start working on molecular phylogenetics and its applications to epidemiology. The course will have theoretical morning sessions followed by small groups practice for a few selected students with their own data. Flyer for the course: CLICK ME

Topics:

  • Introduction to phylogeny: General principles for the inference, interpretation of trees, and application to infectious diseases
  • Introduction to the math behind the trees and evolutionary models
  • Distance and parsimony methods
  • Maximum likelihood methods
  • Bayesian methods, phylodynamics
  • Branch supports, bootstrapping
  • How to select the best method and evolutionary model
  • Tree dating, reconstructing and using character evolution
  • Molecular epidemiology

Teachers:

Chair: Olivier Gascuel, C3BI, Institut Pasteur (France)   Anna Zhukova, C3BI, Institut Pasteur (France) Frédéric Lemoine, C3BI, Institut Pasteur (France) Hein Min Tun, School of Public Health, The University of Hong Kong Julien Guglielmini, C3BI, Institut Pasteur (France) Sebastian Duchene, University of Melbourne (Australia) Tim Vaughan, ETH Zürich (Switzerland) Tommy Lam, School of Public Health, The University of Hong Kong Veronika Boskova, ETH Zürich (Switzerland)

Course dates:

Monday, October 22nd to Saturday, October 27th

Pre-requisites:

  • Basic knowledge on how to use sequence databanks
  • Basic knowledge using Blast and multiple alignments software
  • Basic knowledge on statistics (tests, distributions, parameter estimation)

Applications:

Open to postgraduate students, MD, DVM, postdoctoral fellows and young scientists from Hong Kong and overseas. The course fees are 500HK for the theory sessions and 1000HK for the full course. Students coming from the Institut Pasteur International Network will have the fees waived. Please fill in the following application form before August 14th Midnight (HK time). Use the link if you can’t see the embedded form: https://goo.gl/forms/rgYrUNrEz6rqgELP2)

Unit Seminar – Lucas Husquin & Jakob Ruess

 

EVENT : C3BI Unit Seminars


Main speaker : Lucas Husquin, from Human evolutionary genetics unit Date : 15-02-2018 at 02:00 pm Location : Auditorium Francois Jacob – BIME (26) ,Institut Pasteur, Paris


Lucas Husquin (Human evolutionary genetics unit) : “Dissecting the impact of population variation in DNA methylation on transcriptional responses to immune activation”

&

Jakob Ruess (InBio : Experimental and computational methods for modeling cellular processes) : “Virtual reality for bacteria”


Unit Seminar – Frédéric Lemoine & Lyam Baudry

 

EVENT : C3BI Unit Seminars


Main speaker : Frederic Lemoine from Bioinformatique evolutive Unit Date : 18-01-2018 at 02:00 pm Location : Auditorium Francois Jacob – BIME (26) ,Institut Pasteur, Paris


Frederic Lemoine (Bioinformatique Evolutive) : “Renewing Felsenstein’s Phylogenetic Bootstrap in the Era of Big Data”

&

Lyam Baudry (Spatial Regulation of Genomes) : “Metagenome binning using chromosome conformation capture (3C) data”


Seminars – Emergence of de novo protein coding genes from ‘dark genomic matter’ — fact or fiction?

EVENT : C3BI Seminars

Emergence of de novo protein coding genes from ‘dark genomic matter’ — fact or fiction?


Main speaker : Erich Bornberg-Bauer, from The Westfalian Wilhelms University of Muenster, Germany
Date : 09/11/2017 at 02:00 pm
Location : Auditorium Francois Jacob – BIME (26) ,Institut Pasteur, Paris


Proteins are the workhorses of the cell and, over billions of years, they have evolved an amazing plethora of extremely diverse and versatile structures with equally diverse functions. Therefore, their evolution echoes the evolution of all forms of life. Evolutionary emergence of new proteins and transitions between existing ones are widely believed to be rare or even impossible.
However, recent advances in comparative genomics have repeatedly called some 10%-30% of all genes without any detectable similarity to existing proteins. Even after careful scrutiny, some of those “orphan” genes contain protein coding reading frames with detectable transcription and translation. Thus some proteins seem to have emerged from previously non-coding ‘dark genomic matter’. These ‘de novo’ proteins tend to be disordered, fast evolving, weakly expressed but also rapidly assuming novel and physiologically important functions. I will review mechanisms by which ‘de novo’ proteins might be created, under which circumstances they may become fixed and why they are elusive. I will present a couple of studies which mostly focus on metazoan genomes.


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Publication – Revisiting the taxonomy of the genus Elizabethkingia using whole-genome sequencing, optical mapping, and MALDI-TOF, along with proposal of three novel Elizabethkingia species: Elizabethkingia bruuniana sp. nov., Elizabethkingia ursingii sp. nov., and Elizabethkingia occulta sp. nov

EVENT : C3BI Publication

Revisiting the taxonomy of the genus Elizabethkingia using whole-genome sequencing, optical mapping, and MALDI-TOF, along with proposal of three novel Elizabethkingia species: Elizabethkingia bruuniana sp. nov., Elizabethkingia ursingii sp. nov., and Elizabethkingia occulta sp. nov


Main speaker : , from Date : 01/09/2017 at Location : ,Institut Pasteur, Paris


The genus Elizabethkingia is genetically heterogeneous, and the phenotypic similarities between recognized species pose challenges in correct identification of clinically derived isolates. In addition to the type species Elizabethkingia meningoseptica, and more recently proposed Elizabethkingia miricola, Elizabethkingia anophelis and Elizabethkingia endophytica, four genomospecies have long been recognized. By comparing historic DNA-DNA hybridization results with whole genome sequences, optical maps, and MALDI-TOF mass spectra on a large and diverse set of strains, we propose a comprehensive taxonomic revision of this genus. Genomospecies 1 and 2 contain the type strains E. anophelis and E. miricola, respectively. Genomospecies 3 and 4 are herein proposed as novel species named as Elizabethkingia bruuniana sp. nov. (type strain, G0146(T) = DSM 2975(T) = CCUG 69503(T) = CIP 111191(T)) and Elizabethkingia ursingii sp. nov. (type strain, G4122(T) = DSM 2974(T) = CCUG 69496(T) = CIP 111192(T)), respectively. Finally, the new species Elizabethkingia occulta sp. nov. (type strain G4070(T) = DSM 2976(T) = CCUG 69505(T) = CIP 111193(T)), is proposed.


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Publication – Psychrobacter pasteurii and Psychrobacter piechaudii sp. nov., two novel species within the genus Psychrobacter

EVENT : C3BI Publication

Psychrobacter pasteurii and Psychrobacter piechaudii sp. nov., two novel species within the genus Psychrobacter


Main speaker : , from Date : 28/08/2017 at Location : ,Institut Pasteur, Paris


Six Gram-negative, non-motile, non-spore-forming, non-pigmented, oxidase- and catalase-positive bacterial strains were deposited in 1972, in the Collection of the Institut Pasteur (CIP), Paris, France. The strains, previously identified as members of the genus Moraxella on the basis of their phenotypic and biochemical characteristics, were placed within the genus Psychrobacter based on the results from comparative 16S rRNA gene sequence studies. Their closest phylogenetic relatives were Psychrobacter sanguinis CIP 110993T, Psychrobacter phenylpyruvicus CIP 82.27T and Psychrobacter lutiphocae CIP 110018T. The DNA G+C contents were between 42.1 and 42.7 mol%. The predominant fatty acids were C18 : 1ω9c, C16 : 0, C12 : 0 3-OH, and C18 : 0. Average nucleotide identity between the six strains and their closest phylogenetic relatives, as well as their phenotypic characteristics, supported the assignment of these strains to two novel species within the genus Psychrobacter. The proposed names for these strains are Psychrobacter pasteurii sp. nov., for which the type strain is A1019T (=CIP 110853T=CECT 9184T), and Psychrobacter piechaudii sp. nov., for which the type strain is 1232T (=CIP110854T=CECT 9185T).


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Publication – Real-time whole-genome sequencing for surveillance of Listeria monocytogenes, France.

EVENT : C3BI Publication

Real-time whole-genome sequencing for surveillance of Listeria monocytogenes, France.


Main speaker : , from Date : 19/07/2017 at Location : ,Institut Pasteur, Paris


During 2015-2016, we evaluated the performance of whole-genome sequencing (WGS) as a routine typing tool. Its added value for microbiological and epidemiologic surveillance of listeriosis was compared with that for pulsed-field gel electrophoresis (PFGE), the current standard method. A total of 2,743 Listeria monocytogenes isolates collected as part of routine surveillance were characterized in parallel by PFGE and core genome multilocus sequence typing (cgMLST) extracted from WGS. We investigated PFGE and cgMLST clusters containing human isolates. Discrimination of isolates was significantly higher by cgMLST than by PFGE (p<0.001). cgMLST discriminated unrelated isolates that shared identical PFGE profiles and phylogenetically closely related isolates with distinct PFGE profiles. This procedure also refined epidemiologic investigations to include only phylogenetically closely related isolates, improved source identification, and facilitated epidemiologic investigations, enabling identification of more outbreaks at earlier stages. WGS-based typing should replace PFGE as the primary typing method for L. monocytogenes.


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