Benchmarking network propagation methods for disease gene identification

In-silico identification of potential target genes for disease is an essential aspect of drug target discovery. Recent studies suggest that successful targets can be found through by leveraging genetic, genomic and protein interaction information. Here, we systematically tested the ability of 12 varied algorithms, based on network propagation, to identify genes that have been targeted by any drug, on gene-disease data from 22 common non-cancerous diseases in OpenTargets. We considered two biological networks, six performance metrics and compared two types of input gene-disease association scores. The impact of the design factors in performance was quantified through additive explanatory models. Standard cross-validation led to over-optimistic performance estimates due to the presence of protein complexes. In order to obtain realistic estimates, we introduced two novel protein complex-aware cross-validation schemes. When seeding biological networks with known drug targets, machine learning and diffusion-based methods found around 2-4 true targets within the top 20 suggestions. Seeding the networks with genes associated to disease by genetics decreased performance below 1 true hit on average. The use of a larger network, although noisier, improved overall performance. We conclude that diffusion-based prioritisers and machine learning applied to diffusion-based features are suited for drug discovery in practice and improve over simpler neighbour-voting methods. We also demonstrate the large impact of choosing an adequate validation strategy and the definition of seed disease genesPeer ReviewedPostprint (published version

Demodulation of Spatial Carrier Images: Performance Analysis of Several Algorithms Using a Single Image

http://link.springer.com/article/10.1007%2Fs11340-013-9741-6#Optical full-field techniques have a great importance in modern experimental mechanics. Even if they are reasonably spread among the university laboratories, their diffusion in industrial companies remains very narrow for several reasons, especially a lack of metrological performance assessment. A full-field measurement can be characterized by its resolution, bias, measuring range, and by a specific quantity, the spatial resolution. The present paper proposes an original procedure to estimate in one single step the resolution, bias and spatial resolution for a given operator (decoding algorithms such as image correlation, low-pass filters, derivation tools ...). This procedure is based on the construction of a particular multi-frequential field, and a Bode diagram representation of the results. This analysis is applied to various phase demodulating algorithms suited to estimate in-plane displacements.GDR CNRS 2519 “Mesures de Champs et Identification en Mécanique des Solide

Cell adhesion in free-standing multilayer films made of chitosan and alginate

The method for preparing multilayer ultrathin films by the consecu- tive deposition of oppositely charged polyelectrolytes has gained tre- mendous recognition due the user friendly preparation, capability of incorporating high loads of different types of biomolecules in the films, fine control over the materials’ structure, and robustness of the products under ambient and physiological conditions. However the preparation of such films needs the assembly on a substrate and, sometimes, cannot be detached from it, which has limited the appli- cation of such films in areas as tissue engineering and regenerative medicine (TERM).Thus, the production of free-standing films is of extreme importance once it allows the direct experimental determi- nation of many physical properties of fundamental significance such as ion permeation and mechanical properties that can be tuned for real-world applications. In this work, we investigated the elaboration of free-standing multilayer films made of chitosan (CHI) and alginate (ALG), by detaching a polyelectrolyte multilayer film from its under- lying substrate without any postprocessing step. The conditions for optimized film growth were investigated. The adhesion of C2C12 myoblast cells on the CHI/ALG membrane was assessed by cytoskele- tal and nuclear staining. A good cell adhesion and spreading was observed all over the surface. The results demonstrate the potential of such biocompatible free standing membranes made of CHI and ALG for applications in TERM

Imaging of a vibrating object by Sideband Digital Holography

We obtain quantitative measurements of the oscillation amplitude of vibrating objects by using sideband digital holography. The frequency sidebands on the light scattered by the object, shifted by n times the vibration frequency, are selectively detected by heterodyne holography, and images of the object are calculated for different orders n. Orders up to n=120 have been observed, allowing the measurement of amplitudes of oscillation that are significantly larger than the optical wavelength. Using the positions of the zeros of intensity for each value of n, we reconstruct the shape of vibration the object.Comment: 6 page

Surface probe measurements of the elasticity of sectioned tissue, thin gels and polyelectrolyte multilayer films : correlations between substrate stiffness and cell adhesion

Surface probe measurements of the elasticity of thin-film matrices as well as biological samples prove generally important to understanding cell attachment across such systems. To illustrate this, sectioned arteries were probed by Atomic Force Microscopy (AFM) within the smooth muscle cell (SMC)-rich medial layer, yielding an apparent Young’s modulus Emedia ~ 5-8 kPa. Polyacrylamide gels with Egel spanning several-fold above and below this range were then cast 5-70 μm thick and coated with collagen: SMC spreading shows a hyperbolic dependence in projected cell area versus Egel. The modulus that gives half-max spreading is E1/2-spread ~ 8-10 kPa, proving remarkably close to Emedia. More complex, layer-by-layer micro-films of poly(L-lysine)/hyaluronic acid were also tested and show equivalent trends of increased SMC spreading with increased stiffness. Adhesive spreading of cells thus seems to correlate broadly with the effective stiffness of synthetic materials and tissues

Evolución geodinámica de la fosa del Empordà y las Sierras Transversales

The Emporda basin, together with the half graben system of the Sierras Transversales, form a segment of the European Rift, which is defined here by the NW-SE-trending fault system of northeastern Catalonia.The study area, which partially includes the Sierras Transversales and the southem margin of the Emporda basin, is internally structured by normal faults with listric geometry. Those with measured dip slips of about 1,000 meters are here called main faults; those located in the hanging walls of the main ones are called minor faults, and their dip slips are, at least, lesser in one order of magnitude. The hanging walls of the main faults hold half graben basins, with a sedimentary infill mainly neogene in age in the Emporda, and of quaternay age in the Sierras Transversales. Both areas are geologically bounded by the Camós-Celra fault. This rift segment is also characterized by the occurence of numerous volcanic emission centres. The timing of activity and burial of each fault, constrained by the ages of the associated sediments and vulcanism, suggest a piggy-back sequence of propagation from Miocene to recent times. The geological cross-section constructed from surface data, allowed us the elaboration of a geometric model in clepth for the whole fault system, usiug the inclined shear method. The calculated extension from this method gives us a value of B=1.27. On the other han4 the very high calculated magma ascent rates strongiy constrain the structure in the footwall (crust); subsequently, high angle discontinuities favouring a very fast magmatic ascent have to be definied. These discontinuities would form two imbricate systems (extensional duplexes), with a roof detachment coinciding with the floor detachment of the shallow fault system and a floor detachment located in the MOHO discontinuity. A similar crustal structuration is observed in the neighbouring segment of the Gulf of Lions

Determination of structural parameters characterizing thin films by optical methods: A comparison between scanning angle reflectometry and optical waveguide lightmode spectroscopy

International audienceWe present a comparative study of the structural parameters characterizing thin macromolecular adsorbed films that are obtained from two optical techniques: optical waveguide lightmode spectroscopy ͑OWLS͒ and scanning angle reflectometry ͑SAR͒. We use polyelectrolyte multilayers and polyelectrolyte multilayers/protein films to perform this study. The comparison between the information obtained with the two methods is possible because the buildup of the polyelectrolyte multilayers is known to become substrate independent after the deposition of the first few polyelectrolyte layers. The analysis of the optical data requires usually to postulate a refractive index profile for the interface. Two profiles have been used: the homogeneous and isotropic monolayer and the bilayer profiles. When the refractive index profile of an adsorbed film is well approximated by a homogeneous and isotropic monolayer, as shown by using an analysis of the deposited films in terms of optical invariants, the two optical techniques lead to similar values for the film thickness and the optical mass. The situation is more complex in the case of the multilayers/protein films for which the calculated parameters can strongly depend upon the refractive index profile that is postulated to analyze the optical data. Whereas the optical mass and, to a lesser extent, the thickness seem fairly model independent for OWLS, they appear to be extremely sensitive to the model for SAR. For proteins deposited on top of the polyelectrolyte film, optical mass and protein thickness were found to be comparable when determined by OWLS and by SAR using the bilayer model. The data analysis of the SAR curves with the monolayer model leads to much larger and even physically unreasonable film thicknesses and optical masses. This was particularly noticeable for proteins having a large size ͑human serum albumin and fibrinogen͒, whereas both models lead to similar results for small sized proteins. By means of the different refractive index profiles, we show that great care must be taken in the physicochemical interpretation of the structural parameters determined by these optical techniques

The importance of organizational variables in treatment time for patients with ST-elevation acute myocardial infarction improve delays in STEMI

Background: The time between arrival at the emergency department (ED) and balloon (D2B) in STEMI is one of the best indicators of the quality of care. Our aim is to describe treatment times and evaluate the causes of delay. Methods: This is an observational retrospective study, including all consecutive STEMI code patients ≥18 years old treated in the ED from 2013 to 2016.All the patients were stratified into two groups: delayed group with D2B > 70 min and non-delayed ≤70. The primary variable was D2B time. Findings: In total 327 patients were included, stratified according to their D2B as follows: 166 (67·48%) in the delayed group and 80 (32·52%) in the non-delayed group. The delayed group was older (p = 0·005), with more females (p = 0·060) and more atypical electrocardiogram (ECG) STEMI signs or symptoms (p = 0·058) (p = 0·087). Predictors of shorter D2B time were: typical STEMI ECG signs and short training sessions for nurses on identifying STEMI patients. Interpretation: There are delays particularly in specific groups with atypical clinical presentations. Short training sessions aimed at emergency nurses correlate with shorter delay. This suggests that continuing training for emergency nurses, along with organizational strategies, can contribute to increasing the quality of care. Clinical trial number: NCT0433338

Polyelectrolyte multilayer films with pegylated polypeptides as a new type of anti-microbial protection for biomaterials.

Adhesion of bacteria at the surface of implanted materials is the first step in microbial infection, leading to post-surgical complications. In order to reduce this adhesion, we show that poly(L-lysine)/poly(L-glutamic acid) (PLL/PGA) multilayers ending by several PLL/PGA-g-PEG bilayers can be used, PGA-g-PEG corresponding to PGA grafted by poly(ethylene glycol). Streaming potential and quartz crystal microbalance-dissipation measurements were used to characterize the buildup of these films. The multilayer films terminated by PGA and PGA-g-PEG were found to adsorb an extremely small amount of serum proteins as compared to a bare silica surface but the PGA ending films do not reduce bacterial adhesion. On the other hand, the adhesion of Escherichia coli bacteria is reduced by 72% on films ending by one (PLL/PGA-g-PEG) bilayer and by 92% for films ending by three (PLL/PGA-g-PEG) bilayers compared to bare substrate. Thus, our results show the ability of PGA-g-PEG to be inserted into multilayer films and to drastically reduce both protein adsorption and bacterial adhesion. This kind of anti-adhesive films represents a new and very simple method to coat any type of biomaterials for protection against bacterial adhesion and therefore limiting its pathological consequences.comparative studyevaluation studiesjournal articleresearch support, non-u.s. gov't2004 Mayimporte

Magnetic-responsive hydrogels for cartilage tissue engineering

Publicado em "Journal of Tissue Engineering and Regenerative Medicine", vol. 7, supp. 1 (2013)The use of magnetic nanoparticles (MNPs) has been explored as an alternative approach to overcome current limitations of regenerative medicine strategies. Cell engineering approaches where MNPs are incorporated within three-dimensional constructs, such as scaffolds or hydrogels may constitute a novel and attractive approach towards the development of a magnetically-responsive system. These systems would enable remote controlled actions over tissue engineered constructs in vitro and in vivo. Moreover, growing evidence suggests that the application of a magnetic field may enhance biological performance over commonly used static culture conditions providing stimulation for cell proliferation, migration and differentiation. In this work we analyze the role of magnetic stimulation on the behavior of human adipose derived stem cells (hASCs) laden in k-carrageenan hydrogels aiming at cartilage tissue engineering approaches. Thermo-responsive natural-based κ-carrageenan hydrogels were used as 3D templates since previous studies(1) report the adequate environment provided by these materials to support the viability and chondrogenic differentiation of several types of cells