Equivariant 3D-conditional diffusion model for molecular linker design

Fragment-based drug discovery has been an effective paradigm in early-stage drug development. An open challenge in this area is designing linkers between disconnected molecular fragments of interest to obtain chemically relevant candidate drug molecules. In this work, we propose DiffLinker, an E(3)-equivariant three-dimensional conditional diffusion model for molecular linker design. Given a set of disconnected fragments, our model places missing atoms in between and designs a molecule incorporating all the initial fragments. Unlike previous approaches that are only able to connect pairs of molecular fragments, our method can link an arbitrary number of fragments. Additionally, the model automatically determines the number of atoms in the linker and its attachment points to the input fragments. We demonstrate that DiffLinker outperforms other methods on the standard datasets, generating more diverse and synthetically accessible molecules. We experimentally test our method in real-world applications, showing that it can successfully generate valid linkers conditioned on target protein pockets

La ville métropolisée face aux représentations micropolitaines : pour quels espaces de participation citoyenne ? Étude de cas la Ville de Saint-Égrève

In a context of sociological change and growing importance of taking into account the uses and users of the territories, the question of citizen participation in the process of public policy construction appears to be significant and inherent to the success of projects. How to dispassionately continue public debate in a context of recent registration of the territory with metropolitan logic? Which spaces of participation to adapt ?Dans un contexte de mutation sociologique et de montée en puissance de la prise en compte des usages et usagers des territoires, la question de la participation des citoyens aux processus de construction des politiques publiques apparaît prégnante et inhérente à la réussite des projets. Comment poursuivre sereinement le débat citoyens dans un contexte de récente inscription du territoire aux logiques métropolitaines ? Quels espaces de participations à adapter à ce type de territoire

Learning anisotropic filters on product graphs

The extension of convolutional neural networks to irregular domains has pavedthe way to promising graph data analysis methods. It has however come at theexpense of a reduced representation power, as most of these new network archi-tectures can only learn isotropic filters and therefore often underfit the trainingdata. In this work, we propose a method for building anisotropic filters whenlearning representations of signals on a cartesian product graph. Instead of learn-ing directly on the product graph, we factorize it and learn different filters foreach factor, which is beneficial both in terms of computational cost and expressiv-ity of the filters. We show experimentally that anisotropic Laplacian polynomialsindeed outperform their isotropic counterpart on image classification and matrixcompletion tasks

On The Choice of Graph Neural Network Architectures

Seminal works on graph neural networks have primarily targeted semi-supervised node classification problems with few observed labels and high-dimensional signals. With the development of graph networks, this setup has become a de facto benchmark for a significant body of research. Interestingly, several works have recently shown that in this particular setting, graph neural networks do not perform much better than predefined low-pass filters followed by a linear classifier. However, when learning from little data in a high-dimensional space, it is not surprising that simple and heavily regularized methods are near-optimal. In this paper, we show empirically that in settings with fewer features and more training data, more complex graph networks significantly outperform simple models, and propose a few insights towards the proper choice of graph network architectures. We finally outline the importance of using sufficiently diverse benchmarks (including lower dimensional signals as well) when designing and studying new types of graph neural networks

Ecological risk assessment of Lake Bourget (France, Savoie) littoral sediment contaminated by heavy metals, PAHs and PCBs through chemical analyses, biomarkers, laboratory and in situ bioassays

International audienceIn the early 1980’s, the water level of Lake Bourget (France) was artificially regulated for hydroelectricity. This reduction in the amplitude of fluctuations negatively impacted the development of reed-beds. In autumn 2017, the water level will be lowered in order to stimulate the growth of the reed-beds. We assume that the modifications of the physical conditions of the shallow littoral zone (water depth, oxygen content and redox potential, temperature, …) could change the mobility and bio-availability of contaminants at the water-sediment interface. As a matter of fact, whereas the sediment is generally a sink for contaminants entering the lake, it may act as a source in such changing conditions. The aim of the present work is to assess the basal contamination and ecotoxicity of the sediment of the littoral zone of Lake Bourget in order to study further this phenomenon.For this purpose, we applied a Sediment Quality Triad approach (Chapman, 2000) on sediments from the shoreline of Lake Bourget (France) in order to evaluate their contamination and ecotoxicity. We first characterized the total content of heavy metals (Cd, Cr, Cu, Ni, Pb and Zn), the 16 polycyclic aromatic hydrocarbons (PAHs) identified as priority pollutants by the USEPA and the 7 indicator Polychlorinated biphenyls (PCBs, congeners 28, 52, 101, 118, 138, 153 and 180) in the surface sediment of 10 sites all around the lake. We then conducted laboratory microcosm assays to assess the biological response of cultured species (Lemna minor, Daphnia magna and Chironomus riparius) exposed to these sediments in controlled conditions. Finally, we performed in situ investigations such as biomarker measurements - Acetylcholine-esterase and Glutathione S-Transferase - on the autochthonous macro-fauna (Corbicula fluminea, chironomids, gammarids and oligochaetes) and fitness tests on caged laboratory cladocerans (Daphnia magna). The geographical repartition of the contaminants was mostly in accordance with the pollution sources identified on the watershed. The ecological risk assessment based on Quotient risk and Consensus-Based Sediment Quality Guidelines from MacDonald et al., (2000) showed that sediment from some littoral sites could have a toxic effect on the biota. Despite bio-accumulation of contaminants observed on the laboratory organisms exposed to these sediments and on the autochthonous organisms, no significant toxic effect was observed regarding survival, growth, reproduction, feeding rate endpoints. In addition, biomarker activities measured in the autochthonous benthic organisms did not significantly point out more stressful sites in particular.Our results highlight the importance of studying the biological response of exposed organisms to assess an appropriate ecological risk of a complex mixture of pollutants. The next step will be devoted to the study of contaminants bioavailability and mobility under water level fluctuations, with the assumption that these changes lead to modifications of organisms’ exposure and contaminant bioaccumulation

Ecological risk assessment of Lake Bourget (France, Savoie) littoral sediment contaminated by heavy metals, PAHs and PCBs through chemical analyses, biomarkers, laboratory and in situ bioassays

International audienceIn the early 1980’s, the water level of Lake Bourget (France) was artificially regulated for hydroelectricity. This reduction in the amplitude of fluctuations negatively impacted the development of reed-beds. In autumn 2017, the water level will be lowered in order to stimulate the growth of the reed-beds. We assume that the modifications of the physical conditions of the shallow littoral zone (water depth, oxygen content and redox potential, temperature, …) could change the mobility and bio-availability of contaminants at the water-sediment interface. As a matter of fact, whereas the sediment is generally a sink for contaminants entering the lake, it may act as a source in such changing conditions. The aim of the present work is to assess the basal contamination and ecotoxicity of the sediment of the littoral zone of Lake Bourget in order to study further this phenomenon.For this purpose, we applied a Sediment Quality Triad approach (Chapman, 2000) on sediments from the shoreline of Lake Bourget (France) in order to evaluate their contamination and ecotoxicity. We first characterized the total content of heavy metals (Cd, Cr, Cu, Ni, Pb and Zn), the 16 polycyclic aromatic hydrocarbons (PAHs) identified as priority pollutants by the USEPA and the 7 indicator Polychlorinated biphenyls (PCBs, congeners 28, 52, 101, 118, 138, 153 and 180) in the surface sediment of 10 sites all around the lake. We then conducted laboratory microcosm assays to assess the biological response of cultured species (Lemna minor, Daphnia magna and Chironomus riparius) exposed to these sediments in controlled conditions. Finally, we performed in situ investigations such as biomarker measurements - Acetylcholine-esterase and Glutathione S-Transferase - on the autochthonous macro-fauna (Corbicula fluminea, chironomids, gammarids and oligochaetes) and fitness tests on caged laboratory cladocerans (Daphnia magna). The geographical repartition of the contaminants was mostly in accordance with the pollution sources identified on the watershed. The ecological risk assessment based on Quotient risk and Consensus-Based Sediment Quality Guidelines from MacDonald et al., (2000) showed that sediment from some littoral sites could have a toxic effect on the biota. Despite bio-accumulation of contaminants observed on the laboratory organisms exposed to these sediments and on the autochthonous organisms, no significant toxic effect was observed regarding survival, growth, reproduction, feeding rate endpoints. In addition, biomarker activities measured in the autochthonous benthic organisms did not significantly point out more stressful sites in particular.Our results highlight the importance of studying the biological response of exposed organisms to assess an appropriate ecological risk of a complex mixture of pollutants. The next step will be devoted to the study of contaminants bioavailability and mobility under water level fluctuations, with the assumption that these changes lead to modifications of organisms’ exposure and contaminant bioaccumulation

Vers une meilleure compréhension du comportement des essaims de H. anomala à court terme à l'aide d'une caméra acoustique haute résolution.

International audienceInvasive alien species (IAS) are considered a major cause of biodiversity loss worldwide. The bloody-red shrimp (Hemimysis anomala), an invasive exotic species of the Mysidae family originating from the Ponto-Caspian region, has recently established in peri-alpine lakes. The proliferation of this species is likely to affect both native species and the functioning of lake ecosystems, particularly because of its planktonophagous diet. Due to its nocturnal activity and preference for hard-to-access habitats, still very little is known about its abundance and behaviour. To the best of our knowledge, our study represents the first use of the ARIS Explorer 3000 acoustic camera (Sound Metrics Corp.) with the goal to investigate the in situ behaviour of a typical winter swarm of H. anomala. The results of this study demonstrate the ability to detect the animal and obtain high-frequency data, the possibility to estimate its quantitative importance, and monitor its behaviour in detail. Also, the acquisition of such short-term observations, spanning several days to weeks, allowed us to assess the importance and role of various environmental factors on shrimp abundance aiming to characterize the determinism of its nocturnal activity.Les espèces exotiques envahissantes sont considérées comme une cause importante de la perte de la biodiversité au niveau mondial. La crevette rouge sang (Hemimysis anomala), espèce exotique de la famille des Mysidacés au caractère envahissant, originaire de la région ponto-caspienne, s’est récemment installée dans les grands lacs périalpins. La prolifération de cette espèce peut avoir un impact sur le fonctionnement des écosystèmes lacustres et sur les espèces natives, particulièrement en raison de son régime alimentaire planctonophage. Du fait de son activité nocturne, et de son affinité pour les habitats difficiles d’accès, l’évaluation de son abondance et de son comportement restent très mal connues. À notre connaissance, notre étude présente la première utilisation de la caméra acoustique ARIS Explorer 3000 (Sound Metrics Corp.) dans le but d’étudier le comportement in situ d’Hemimysis anomala. Les résultats de cette étude révèlent que nous pouvons détecter la crevette rouge sang et obtenir des données à haute fréquence, estimer son importance quantitative et suivre son comportement de manière très fine. L’obtention de ces observations, à court terme, pendant plusieurs jours à semaines, nous a également permis de tester l’importance et le rôle de différents facteurs environnementaux sur les variations d’abondance des crevettes afin de caractériser le déterminisme de son activité nycthémérale

Faisabilité de l’étude de la crevette invasive Hemimysis anomala par caméra acoustique

Les espèces exotiques envahissantes sont considérées comme une cause importante de la perte de la biodiversité au niveau mondial. La crevette rouge sang (Hemimysis anomala), espèce exotique de la famille des Mysidacés au caractère envahissant, originaire de la région ponto-caspienne, s’est récemment installée dans les grands lacs périalpins. La prolifération de cette espèce peut avoir un impact sur le fonctionnement des écosystèmes lacustres et sur les espèces natives, particulièrement en raison de son régime alimentaire planctonophage. Du fait de son activité nocturne et de son affinité pour les habitats difficiles d’accès, l’évaluation de son abondance et de son comportement reste mal connue. Notre étude présente la faisabilité d’étudier le comportement in situ d’Hemimysis anomala à l’aide d’une caméra acoustique ARIS Explorer 3000 (Sound Metrics Corp.). Les résultats révèlent que nous pouvons détecter la crevette rouge sang et obtenir des données à haute fréquence et suivre ainsi son comportement de manière très fine

Faisabilité de l’étude de la crevette invasive Hemimysis anomala par caméra acoustique

Les espèces exotiques envahissantes sont considérées comme une cause importante de la perte de la biodiversité au niveau mondial. La crevette rouge sang (Hemimysis anomala), espèce exotique de la famille des Mysidacés au caractère envahissant, originaire de la région ponto-caspienne, s’est récemment installée dans les grands lacs périalpins. La prolifération de cette espèce peut avoir un impact sur le fonctionnement des écosystèmes lacustres et sur les espèces natives, particulièrement en raison de son régime alimentaire planctonophage. Du fait de son activité nocturne et de son affinité pour les habitats difficiles d’accès, l’évaluation de son abondance et de son comportement reste mal connue. Notre étude présente la faisabilité d’étudier le comportement in situ d’Hemimysis anomala à l’aide d’une caméra acoustique ARIS Explorer 3000 (Sound Metrics Corp.). Les résultats révèlent que nous pouvons détecter la crevette rouge sang et obtenir des données à haute fréquence et suivre ainsi son comportement de manière très fine