Immunodepression and Immunosuppression During Aging

International audienc

Active regulatory T-cells contribute to broadened T-cell repertoire diversity in ivIg-treated SLE patients

Octapharma

Broadened T-cell Repertoire Diversity in ivIg-treated SLE Patients is Also Related to the Individual Status of Regulatory T-cells

Intravenous IgG (ivIg) is a therapeutic alternative for lupus erythematosus, the mechanism of which remains to be fully understood. Here we investigated whether ivIg affects two established sub-phenotypes of SLE, namely relative oligoclonality of circulating T-cells and reduced activity of CD4 + Foxp3+ regulatory T-cells (Tregs) reflected by lower CD25 surface density.Octapharma research funding; Fundação para a Ciência e a Tecnologia postdoctoral fellowships: (SFRH/BPD/20806/2004, SFRH/BPD/34648/2007); FCT Programa Pessoa travel grant

French Roadmap for complex Systems 2008-2009

This second issue of the French Complex Systems Roadmap is the outcome of the Entretiens de Cargese 2008, an interdisciplinary brainstorming session organized over one week in 2008, jointly by RNSC, ISC-PIF and IXXI. It capitalizes on the first roadmap and gathers contributions of more than 70 scientists from major French institutions. The aim of this roadmap is to foster the coordination of the complex systems community on focused topics and questions, as well as to present contributions and challenges in the complex systems sciences and complexity science to the public, political and industrial spheres

State-transition diagrams for biologists.

It is clearly in the tradition of biologists to conceptualize the dynamical evolution of biological systems in terms of state-transitions of biological objects. This paper is mainly concerned with (but obviously not limited too) the immunological branch of biology and shows how the adoption of UML (Unified Modeling Language) state-transition diagrams can ease the modeling, the understanding, the coding, the manipulation or the documentation of population-based immune software model generally defined as a set of ordinary differential equations (ODE), describing the evolution in time of populations of various biological objects. Moreover, that same UML adoption naturally entails a far from negligible representational economy since one graphical item of the diagram might have to be repeated in various places of the mathematical model. First, the main graphical elements of the UML state-transition diagram and how they can be mapped onto a corresponding ODE mathematical model are presented. Then, two already published immune models of thymocyte behavior and time evolution in the thymus, the first one originally conceived as an ODE population-based model whereas the second one as an agent-based one, are refactored and expressed in a state-transition form so as to make them much easier to understand and their respective code easier to access, to modify and run. As an illustrative proof, for any immunologist, it should be possible to understand faithfully enough what the two software models are supposed to reproduce and how they execute with no need to plunge into the Java or Fortran lines

RepSeq Data Representativeness and Robustness Assessment by Shannon Entropy

High-throughput sequencing (HTS) has the potential to decipher the diversity of T cell repertoires and their dynamics during immune responses. Applied to T cell subsets such as T effector and T regulatory cells, it should help identify novel biomarkers of diseases. However, given the extreme diversity of TCR repertoires, understanding how the sequencing conditions, including cell numbers, biological and technical sampling and sequencing depth, impact the experimental outcome is critical to proper use of these data. Here, we assessed the representativeness and robustness of TCR repertoire diversity assessment according to experimental conditions. By comparative analyses of experimental datasets and computer simulations, we found that (i) for small samples, the number of clonotypes recovered is often higher than the number of cells per sample, even after removing the singletons; (ii) high-sequencing depth for small samples alters the clonotype distributions, which can be corrected by filtering the datasets using Shannon entropy as a threshold; and (iii) a single sequencing run at high depth does not ensure a good coverage of the clonotype richness in highly polyclonal populations, which can be better covered using multiple sequencing. Altogether, our results warrant better understanding and awareness of the limitation of TCR diversity analyses by HTS and justify the development of novel computational tools for improved modeling of the highly complex nature of TCR repertoires

Dynamical and Mechanistic Reconstructive Approaches of T Lymphocyte Dynamics: Using Visual Modeling Languages to Bridge the Gap between Immunologists, Theoreticians, and Programmers

International audienceDynamic modeling of lymphocyte behavior has primarily been based on populations based differential equations or on cellular agents moving in space and interacting each other. The final steps of this modeling effort are expressed in a code written in a programing language. On account of the complete lack of standardization of the different steps to proceed, we have to deplore poor communication and sharing between experimentalists, theoreticians and programmers. The adoption of diagrammatic visual computer language should however greatly help the immunologists to better communicate, to more easily identify the models similarities and facilitate the reuse and extension of existing software models. Since immunologists often conceptualize the dynamical evolution of immune systems in terms of “state-transitions” of biological objects, we promote the use of unified modeling language (UML) state-transition diagram. To demonstrate the feasibility of this approach, we present a UML refactoring of two published models on thymocyte differentiation. Originally built with different modeling strategies, a mathematical ordinary differential equation-based model and a cellular automata model, the two models are now in the same visual formalism and can be compared.

OntoContext, a new python package for gene contextualization based on the annotation of biomedical texts

Motivation : The automatic mining for bibliography exploitation in given contexts is a challenge according to the increasing number of scientific publications and new concepts. Several indexing systems were developed for biomedical literature. However, such systems have failed to produce contextualised research of genes and proteins and automatically group texts according to shared concepts. In this paper, we present OntoContext, a contextualization system crossing the use of biomedical ontologies to annotate texts containing terms related to cell populations, anatomical locations and diseases and to extract gene, RNA or protein names in these contexts. Results : OntoContext, a new python package contains two modules. The “annot” module for “annotation” function, is based on combination of morphosyntactic labelling and exact matching and on dictionaries derived from the Cell Ontology, the UBERON Ontology (anatomical context), the Human Disease Ontology and geniatagger, (which contains particular tags for gene-related names). The “annot” output is used as input for the second module “crisscross” generating lists of gene-related names obtained by crossing annotations from the three mentioned ontologies. OntoContext showed better performances than NCBO Annotator after evaluation on two text corpuses. OntoContext is freely available in the pypi

Sensitivity of Alpine glaciers to anthropogenic atmospheric forcings: case study of the Argentière glacier

This study aims at quantifying the contribution of external climate forcings on the retreat of the Argentière glacier (Mont-Blanc area). Its evolution is simulated over 1850-2014 following retrospective scenarios produced with the IPSL-CM6-LR climate model, excluding and including natural and anthropogenic forcings. These scenarios are statistically adjusted at the local scale, ensuring a preservation of the long-term trends and a physical consistency between precipitation and temperature, to finally force an ice flow model coupled with a surface mass balance scheme. The regional aerosol cooling partly counteracted the greenhouse gases warming, delaying the time of emergence of anthropogenic signals: The anthropogenic influences emerged from the natural variability in 1979 for temperature and in 2008 for the mass of the glacier, whereas its snout position in 2014 remains compatible with natural variability. We found that 66% [20-112%] of the total mass loss in 2014 since 1850 can be attributed to anthropogenic activities