Publications

Analysis of gene expression and use of connectivity mapping to identify drugs for treatment of human glomerulopathies
Chen-Fang Chung
Joan Papillon
José R. Navarro-Betancourt
Julie Guillemette
Ameya Bhope
Amin Emad
Andrey V. Cybulsky
2023-03-12
Frontiers in Medicine (published)
doi.org
Applying the column generation method to the intensity modulated high dose rate brachytherapy inverse planning problem
Majd Antaki
Marc-André Renaud
Marc Morcos
Jan Seuntjens
S. Enger
2023-03-12
Physics in Medicine & Biology (published)
doi.org
Investigating the neural correlates of affective mentalizing and their association with general intelligence in patients with schizophrenia
Wladimir Tantchik
Melissa J. Green
Yann Quidé
Susanne Erk
Sebastian Mohnke
Carolin Wackerhagen
Nina Romanczuk-Seiferth
Heike Tost
Kristina Schwarz
Carolin Moessnang
Danilo Bzdok
Andreas Meyer-Lindenberg
Andreas Heinz
Henrik Walter
2023-03-12
Schizophrenia Research (unknown)
doi.org
Optimization of the location and design of urban green spaces
Caroline Leboeuf
Margarida Carvalho
Yan Kestens
Benoit Thierry
2023-03-12
ArXiv (preprint)
doi.org
arxiv.org
Proactive Contact Tracing
Prateek Gupta
Tegan Maharaj
Martin Weiss
Nasim Rahaman
Hannah Alsdurf
Nanor Minoyan
Soren Harnois-Leblanc
Joanna Merckx
Andrew Williams
Victor Schmidt
Pierre-Luc St-Charles
Akshay Patel
Yang Zhang
David L. Buckeridge
Christopher Pal
Bernhard Schölkopf
Yoshua Bengio
The COVID-19 pandemic has spurred an unprecedented demand for interventions that can reduce disease spread without excessively restricting d… (see more)aily activity, given negative impacts on mental health and economic outcomes. Digital contact tracing (DCT) apps have emerged as a component of the epidemic management toolkit. Existing DCT apps typically recommend quarantine to all digitally-recorded contacts of test-confirmed cases. Over-reliance on testing may, however, impede the effectiveness of such apps, since by the time cases are confirmed through testing, onward transmissions are likely to have occurred. Furthermore, most cases are infectious over a short period; only a subset of their contacts are likely to become infected. These apps do not fully utilize data sources to base their predictions of transmission risk during an encounter, leading to recommendations of quarantine to many uninfected people and associated slowdowns in economic activity. This phenomenon, commonly termed as “pingdemic,” may additionally contribute to reduced compliance to public health measures. In this work, we propose a novel DCT framework, Proactive Contact Tracing (PCT), which uses multiple sources of information (e.g. self-reported symptoms, received messages from contacts) to estimate app users’ infectiousness histories and provide behavioral recommendations. PCT methods are by design proactive, predicting spread before it occurs. We present an interpretable instance of this framework, the Rule-based PCT algorithm, designed via a multi-disciplinary collaboration among epidemiologists, computer scientists, and behavior experts. Finally, we develop an agent-based model that allows us to compare different DCT methods and evaluate their performance in negotiating the trade-off between epidemic control and restricting population mobility. Performing extensive sensitivity analysis across user behavior, public health policy, and virological parameters, we compare Rule-based PCT to i) binary contact tracing (BCT), which exclusively relies on test results and recommends a fixed-duration quarantine, and ii) household quarantine (HQ). Our results suggest that both BCT and Rule-based PCT improve upon HQ, however, Rule-based PCT is more efficient at controlling spread of disease than BCT across a range of scenarios. In terms of cost-effectiveness, we show that Rule-based PCT pareto-dominates BCT, as demonstrated by a decrease in Disability Adjusted Life Years, as well as Temporary Productivity Loss. Overall, we find that Rule-based PCT outperforms existing approaches across a varying range of parameters. By leveraging anonymized infectiousness estimates received from digitally-recorded contacts, PCT is able to notify potentially infected users earlier than BCT methods and prevent onward transmissions. Our results suggest that PCT-based applications could be a useful tool in managing future epidemics.
2023-03-12
PLOS Digital Health (published)
doi.org
Neural manifolds and learning regimes in neural-interface tasks
Alexandre Payeur
Amy L. Orsborn
Guillaume Lajoie
Neural activity tends to reside on manifolds whose dimension is lower than the dimension of the whole neural state space. Experiments using … (see more)brain-computer interfaces (BCIs) with microelectrode arrays implanted in the motor cortex of nonhuman primates have provided ways to test whether neural manifolds influence learning-related neural computations. Starting from a learned BCI-controlled motor task, these experiments explored the effect of changing the BCI decoder to implement perturbations that were either “aligned” or not with the pre-existing neural manifold. In a series of studies, researchers found that within-manifold perturbations (WMPs) evoked fast reassociations of existing neural patterns for rapid adaptation, while outside-manifold perturbations (OMPs) triggered a slower adaptation process that led to the emergence of new neural patterns. Together, these findings have been interpreted as suggesting that these different rates of adaptation might be associated with distinct learning mechanisms. Here, we investigated whether gradient-descent learning could alone explain these differences. Using an idealized model that captures the fixed-point dynamics of recurrent neural networks, we uncovered gradient-based learning dynamics consistent with experimental findings. Crucially, this experimental match arose only when the network was initialized in a lazier learning regime, a concept inherited from deep learning theory. A lazy learning regime—in contrast with a rich regime—implies small changes on synaptic strengths throughout learning. For OMPs, these small changes were less effective at increasing performance and could lead to unstable adaptation with a heightened sensitivity to learning rates. For WMPs, they helped reproduce the reassociation mechanism on short adaptation time scales, especially with large input variances. Since gradient descent has many biologically plausible variants, our findings establish lazy gradient-based learning as a plausible mechanism for adaptation under network-level constraints and unify several experimental results from the literature.
2023-03-11
bioRxiv (preprint)
doi.org
A Systematic Study of Joint Representation Learning on Protein Sequences and Structures
Zuobai Zhang
Chuanrui Wang
Minghao Xu
Vijil Chenthamarakshan
Aurelie Lozano
Payel Das
Jian Tang
Learning effective protein representations is critical in a variety of tasks in biology such as predicting protein functions. Recent sequenc… (see more)e representation learning methods based on Protein Language Models (PLMs) excel in sequence-based tasks, but their direct adaptation to tasks involving protein structures remains a challenge. In contrast, structure-based methods leverage 3D structural information with graph neural networks and geometric pre-training methods show potential in function prediction tasks, but still suffers from the limited number of available structures. To bridge this gap, our study undertakes a comprehensive exploration of joint protein representation learning by integrating a state-of-the-art PLM (ESM-2) with distinct structure encoders (GVP, GearNet, CDConv). We introduce three representation fusion strategies and explore different pre-training techniques. Our method achieves significant improvements over existing sequence- and structure-based methods, setting new state-of-the-art for function annotation. This study underscores several important design choices for fusing protein sequence and structure information. Our implementation is available at https://github.com/DeepGraphLearning/ESM-GearNet.
2023-03-10
ArXiv (preprint)
arxiv.org
arxiv.org
Molecular pathology of acute respiratory distress syndrome, mechanical ventilation and abnormal coagulation in severe COVID-19
Antoine Soulé
William Ma
Katelyn Yixiu Liu
Catherine Allard
Salman Qureshi
Karine Tremblay
Amin Emad
Simon Rousseau
Systemic inflammation in critically ill patients can lead to serious consequences such as acute respiratory distress syndrome (ARDS), a cond… (see more)ition characterized by the presence of lung inflammation, edema, and impaired gas exchange, associated with poor survival. Understanding molecular pathobiology is essential to improve critical care of these patients. To this end, we use multimodal profiles of SARS-CoV-2 infected hospitalized participants to the Biobanque Québécoise de la COVID-19 (BQC-19) to characterize endophenotypes associated with different degrees of disease severity. Proteomic, metabolomic, and genomic characterization supported a role for neutrophil-associated procoagulant activity in severe COVID-19 ARDS that is inversely correlated with sphinghosine-1 phosphate plasma levels. Fibroblast Growth Factor Receptor (FGFR) and SH2-containing transforming protein 4 (SHC4) signaling were identified as molecular features associated with endophenotype 6 (EP6). Mechanical ventilation in EP6 was associated with alterations in lipoprotein metabolism. These findings help define the molecular mechanisms related to specific severe outcomes, that can be used to identify early unfavorable clinical trajectories and treatable traits to improve the survival of critically ill patients.
2023-03-09
medRxiv (preprint)
doi.org
The Critical Node Game
Gabriele Dragotto
Amine Boukhtouta
Andrea Lodi
Mehdi Taobane
Cloud networks are the backbone of the modern distributed internet infrastructure as they provision most of the on-demand resources organiza… (see more)tions and individuals use daily. However, any abrupt cyber-attack could disrupt the provisioning of some of the cloud resources fulfilling the needs of customers, industries, and governments. In this work, we introduce a game-theoretic model that assesses the cyber-security risk of cloud networks and informs security experts on the optimal security strategies. Our approach combines game theory, combinatorial optimization, and cyber-security and aims at minimizing the unexpected network disruptions caused by malicious cyber-attacks under uncertainty. Methodologically, our approach consists of a simultaneous and non-cooperative attacker-defender game where each player solves a combinatorial optimization problem parametrized in the variables of the other player. Practically, our approach enables security experts to (i.) assess the security posture of the cloud network, and (ii.) dynamically adapt the level of cyber-protection deployed on the network. We provide a detailed analysis of a real-world cloud network and demonstrate the efficacy of our approach through extensive computational tests.
2023-03-09
ArXiv (preprint)
doi.org
arxiv.org
Transfer Entropy Bottleneck: Learning Sequence to Sequence Information Transfer
Damjan Kalajdzievski
Ximeng Mao
Pascal Fortier-Poisson
Guillaume Lajoie
Blake A. Richards
When presented with a data stream of two statistically dependent variables, predicting the future of one of the variables (the target stream… (see more)) can benefit from information about both its history and the history of the other variable (the source stream). For example, fluctuations in temperature at a weather station can be predicted using both temperatures and barometric readings. However, a challenge when modelling such data is that it is easy for a neural network to rely on the greatest joint correlations within the target stream, which may ignore a crucial but small information transfer from the source to the target stream. As well, there are often situations where the target stream may have previously been modelled independently and it would be useful to use that model to inform a new joint model. Here, we develop an information bottleneck approach for conditional learning on two dependent streams of data. Our method, which we call Transfer Entropy Bottleneck (TEB), allows one to learn a model that bottlenecks the directed information transferred from the source variable to the target variable, while quantifying this information transfer within the model. As such, TEB provides a useful new information bottleneck approach for modelling two statistically dependent streams of data in order to make predictions about one of them.
2023-03-07
Transactions on Machine Learning Research (accepted)
doi.org
openreview.net
A cognitive fingerprint in human random number generation
Marc-Andre Schulz
Sebastian Baier
Benjamin Timmermann
Danilo Bzdok
Karsten Witt

Most work in the neurosciences collapses data from multiple subjects to obtain robust statistical results. This research agenda ignores t… (see more)hat even in healthy subjects brain structure and function are known to be highly variable. Recently, Finn and colleagues showed that the brain's functional organisation is unique to each individual and can yield human-specific connectome fingerprints. This raises the question whether unique functional brain architecture may reflect a unique implementation of cognitive processes and problem solving - i.e. "Can we identify single individuals based on how they think?". The present study addresses the general question of interindividual differences in the specific context of human random number generation. We analyzed the deployment of recurrent patterns in the pseudorandom sequences to develop an identification scheme based on subject-specific volatility patterns. We demonstrate that individuals can be reliably identified based on how they how they generate randomness patterns alone. We moreover show that this phenomenon is driven by individual preference and inhibition of patterns, together forming a cognitive fingerprint.

2023-03-06
Charité - Universitätsmedizin Berlin (published)
doi.org
Enhancing Protein Language Model with Structure-based Encoder and Pre-training
Zuobai Zhang
Minghao Xu
Aurelie Lozano
Vijil Chenthamarakshan
Payel Das
Jian Tang
Protein language models (PLMs) pre-trained on large-scale protein sequence corpora have achieved impressive performance on various downstrea… (see more)m protein understanding tasks. Despite the ability to implicitly capture inter-residue contact information, transformer-based PLMs cannot encode protein structures explicitly for better structure-aware protein representations. Besides, the power of pre-training on available protein structures has not been explored for improving these PLMs, though structures are important to determine functions. To tackle these limitations, in this work, we enhance the PLM with structure-based encoder and pre-training. We first explore feasible model architectures to combine the advantages of a state-of-the-art PLM (i.e., ESM-1b) and a state-of-the-art protein structure encoder (i.e., GearNet). We empirically verify the ESM-GearNet that connects two encoders in a series way as the most effective combination model. To further improve the effectiveness of ESM-GearNet, we pre-train it on massive unlabeled protein structures with contrastive learning, which aligns representations of co-occurring subsequences so as to capture their biological correlation. Extensive experiments on EC and GO protein function prediction benchmarks demonstrate the superiority of ESM-GearNet over previous PLMs and structure encoders, and clear performance gains are further achieved by structure-based pre-training upon ESM-GearNet. The source code will be made public upon acceptance.
2023-03-05
ICLR.cc/2023/Workshop/MLDD (poster)
openreview.net
openreview.net