Peu importe la taille : démocratiser la découverte de protéines avec l'IA
Des chercheurs de Mila ont créé un puissant modèle de langage protéique à source ouverte plus compact et efficace afin de démocratiser la découverte de protéines.
La prochaine cohorte de notre programme, conçu pour fournir aux participant·e·s une compréhension fondamentale des technologies de l'IA, se déroulera à Ottawa les 28 et 29 novembre.
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Publications
Endocytic proteins with prion-like domains form viscoelastic condensates that enable membrane remodeling
Significance The uptake of molecules into cells, known as endocytosis, requires membrane invagination and the formation of vesicles. A versi… (voir plus)on of endocytosis that is independent of actin polymerization is aided by the assembly of membraneless biomolecular condensates at the site of membrane invagination. Here, we show that endocytic condensates are viscoelastic bodies that concentrate key proteins with prion-like domains to enable membrane remodeling. A distinct molecular grammar, namely the preference for glutamine versus asparagine residues, underlies the cohesive interactions that give rise to endocytic condensates. We incorporate material properties inferred using active rheology into a mechanical model to explain how cohesive interactions within condensates and interfacial tensions among condensates, membranes, and the cytosol can drive membrane invagination to initiate endocyosis. Membrane invagination and vesicle formation are key steps in endocytosis and cellular trafficking. Here, we show that endocytic coat proteins with prion-like domains (PLDs) form hemispherical puncta in the budding yeast, Saccharomyces cerevisiae. These puncta have the hallmarks of biomolecular condensates and organize proteins at the membrane for actin-dependent endocytosis. They also enable membrane remodeling to drive actin-independent endocytosis. The puncta, which we refer to as endocytic condensates, form and dissolve reversibly in response to changes in temperature and solution conditions. We find that endocytic condensates are organized around dynamic protein–protein interaction networks, which involve interactions among PLDs with high glutamine contents. The endocytic coat protein Sla1 is at the hub of the protein–protein interaction network. Using active rheology, we inferred the material properties of endocytic condensates. These experiments show that endocytic condensates are akin to viscoelastic materials. We use these characterizations to estimate the interfacial tension between endocytic condensates and their surroundings. We then adapt the physics of contact mechanics, specifically modifications of Hertz theory, to develop a quantitative framework for describing how interfacial tensions among condensates, the membrane, and the cytosol can deform the plasma membrane to enable actin-independent endocytosis.
2021-12-09
Proceedings of the National Academy of Sciences of the United States of America (publié)
Mortality trends and lengths of stay among hospitalized COVID-19 patients in Ontario and Quebec (Canada): a population-based cohort study of the first three epidemic waves
Background: Epidemic waves of COVID-19 strained hospital resources. We describe temporal trends in mortality risk and length of stay in inte… (voir plus)nsive cares units (ICUs) among COVID-19 patients hospitalized through the first three epidemic waves in Canada. Methods: We used population-based provincial hospitalization data from Ontario and Québec to examine mortality risk and lengths of ICU stay. For each province, adjusted estimates were obtained using marginal standardization of logistic regression models, adjusting for patient-level characteristics and hospital-level determinants. Results: Using all hospitalizations from Ontario (N=26,541) and Québec (N=23,857), we found that unadjusted in-hospital mortality risks peaked at 31% in the first wave and was lowest at the end of the third wave at 6-7%. This general trend remained after controlling for confounders. The odds of in-hospital mortality in the highest hospital occupancy quintile was 1.2 (95%CI: 1.0-1.4; Ontario) and 1.6 (95%CI: 1.3-1.9; Québec) times that of the lowest quintile. Variants of concerns were associated with an increased in-hospital mortality. Length of ICU stay decreased over time from a mean of 16 days (SD=18) to 15 days (SD=15) in the third wave but were consistently higher in Ontario than Québec by 3-6 days. Conclusion: In-hospital mortality risks and lengths of ICU stay declined over time in both provinces, despite changing patient demographics, suggesting that new therapeutics and treatment, as well as improved clinical protocols, could have contributed to this reduction. Continuous population-based monitoring of patient outcomes in an evolving epidemic is necessary for health system preparedness and response.
In modern days, social media platforms provide accessible channels for the inter-action and immediate reflection of the most important event… (voir plus)s happening around the world. In this paper, we, firstly, present a curated set of datasets whose origin stem from the Twitter’s Information Operations efforts. More notably, these accounts, which have been already suspended, provide a notion of how state-backed human trolls operate.Secondly, we present detailed analyses of how these behaviours vary over time,and motivate its use and abstraction in the context of deep representation learning:for instance, to learn and, potentially track, troll behaviour. We present baselinesf or such tasks and highlight the differences there may exist within the literature.Finally, we utilize the representations learned for behaviour prediction to classify trolls from"real"users, using a sample of non-suspended active accounts.
2021-12-07
LatinX in AI at Neural Information Processing Systems Conference 2021 (publié)
Patient health records and whole viral genomes from an early SARS-CoV-2 outbreak in a Quebec hospital reveal features associated with favorable outcomes
In today’s age of (mis)information, many people utilize various social media platforms in an attempt to shape public opinion on several im… (voir plus)portant issues, including elections and the COVID-19 pandemic. These two topics have recently become intertwined given the importance of complying with public health measures related to COVID-19 and politicians’ management of the pandemic. Motivated by this, we study the partisan polarization of COVID-19 discussions on social media. We propose and utilize a novel measure of partisan polarization to analyze more than 380 million posts from Twitter and Parler around the 2020 US presidential election. We find strong correlation between peaks in polarization and polarizing events, such as the January 6th Capitol Hill riot. We further classify each post into key COVID-19 issues of lockdown, masks, vaccines, as well as miscellaneous, to investigate both the volume and polarization on these topics and how they vary through time. Parler includes more negative discussions around lockdown and masks, as expected, but not much around vaccines. We also observe more balanced discussions on Twitter and a general disconnect between the discussions on Parler and Twitter.
2021-12-01
2021 International Conference on Data Mining Workshops (ICDMW) (publié)
Background. Sensory processing atypicalities are part of the core symptoms of autism spectrum disorder (ASD) and could result from an excita… (voir plus)tion/inhibition imbalance. Yet, the convergence level of phenotypic sensory processing atypicalities with genetic alterations in GABA-ergic and glutamatergic pathways remains poorly understood. This study aimed to characterize the distribution of hypo/hyper-sensory profile among individuals with ASD and investigate the role of deleterious mutations in GABAergic and glutamatergic pathways related genes in sensory processing atypicalities. Method. From the Short Sensory Profile (SSP) questionnaire, we defined and explored a score – the differential Short Sensory Profile (dSSP) - as a normalized and centralized hypo/hypersensitivity ratio for 1136 participants (533 with ASD, 210 first-degree relatives, and 267 controls) from two independent study samples (PARIS and LEAP). We also performed an unsupervised item-based clustering analysis on SSP items scores to validate this new categorization in terms of hypo and hyper sensitivity. We then explored the link between the dSSP score and the burden of deleterious mutations in a subset of individuals for which whole-genome sequencing data were available. Results. We observed a mean dSSP score difference between ASD and controls, driven mostly by a high dSSP score variability among groups (PARIS: p0.0001, η2 = 0.0001, LEAP: p0.0001, Cohen’s d=3.67). First-degree relatives were with an intermediate distribution variability prof
Anomaly detection is of great interest in fields where abnormalities need to be identified and corrected (e.g., medicine and finance). Deep … (voir plus)learning methods for this task often rely on autoencoder reconstruction error, sometimes in conjunction with other penalties. We show that this approach exhibits intrinsic biases that lead to undesirable results. Reconstruction-based methods can sometimes show low error on simple-to-reconstruct points that are not part of the training data, for example the all black image. Instead, we introduce a new unsupervised Lipschitz anomaly discriminator (LAD) that does not suffer from these biases. Our anomaly discriminator is trained, similar to the discriminator of a GAN, to detect the difference between the training data and corruptions of the training data. We show that this procedure successfully detects unseen anomalies with guarantees on those that have a certain Wasserstein distance from the data or corrupted training set. These additions allow us to show improved performance on MNIST, CIFAR10, and health record data. Further, LAD does not require decoding back to the original data space, which makes anomaly detection possible in domains where it is difficult to define a decoder, such as in irregular graph structured data. Empirically, we show this framework leads to improved performance on image, health record, and graph data.
In recent years there has been a resurgence of interest in our community in the shape analysis of 3D objects repre-sented by surface meshes,… (voir plus) their voxelized interiors, or surface point clouds. In part, this interest has been stimulated by the increased availability of RGBD cameras, and by applications of computer vision to autonomous driving, medical imaging, and robotics. In these settings, spectral co-ordinates have shown promise for shape representation due to their ability to incorporate both local and global shape properties in a manner that is qualitatively invariant to iso-metric transformations. Yet, surprisingly, such coordinates have thus far typically considered only local surface positional or derivative information. In the present article, we propose to equip spectral coordinates with medial (object width) information, so as to enrich them. The key idea is to couple surface points that share a medial ball, via the weights of the adjacency matrix. We develop a spectral feature using this idea, and the algorithms to compute it. The incorporation of object width and medial coupling has direct benefits, as illustrated by our experiments on object classification, object part segmentation, and surface point correspondence.
Transfer learning from large-scale pre-trained models has become essential for many computer vision tasks. Recent studies have shown that da… (voir plus)tasets like ImageNet are weakly labeled since images with multiple object classes present are assigned a single label. This ambiguity biases models towards a single prediction, which could result in the suppression of classes that tend to co-occur in the data. Inspired by language emergence literature, we propose multi-label iterated learning (MILe) to incorporate the inductive biases of multi-label learning from single labels using the framework of iterated learning. MILe is a simple yet effective procedure that builds a multi-label description of the image by propagating binary predictions through successive generations of teacher and student networks with a learning bottleneck. Experiments show that our approach exhibits systematic benefits on ImageNet accuracy as well as ReaL F1 score, which indicates that MILe deals better with label ambiguity than the standard training procedure, even when fine-tuning from self-supervised weights. We also show that MILe is effective reducing label noise, achieving state-of-the-art performance on real-world large-scale noisy data such as WebVision. Furthermore, MILe improves performance in class incremental settings such as IIRC and it is robust to distribution shifts. Code: https://github.com/rajeswar18/MILe