Publications

A Systematic Study of Joint Representation Learning on Protein Sequences and Structures

Zuobai Zhang

Chuanrui Wang

Minghao Xu

Vijil Chenthamarakshan

Aurelie Lozano

Payel Das

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.

2023-03-11

ArXiv (preprint)

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.

2023-03-10

ArXiv (preprint)

Transfer Entropy Bottleneck: Learning Sequence to Sequence Information Transfer

Damjan Kalajdzievski

Ximeng Mao

Pascal Fortier-Poisson

Guillaume Lajoie

Blake 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.

2023-03-08

TMLR (accepted)

Enhancing Protein Language Model with Structure-based Encoder and Pre-training

Zuobai Zhang

Minghao Xu

Aurelie Lozano

Vijil Chenthamarakshan

Payel Das

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.

2023-03-06

ICLR.cc/2023/Workshop/MLDD (poster)

Enhancing Protein Language Model with Structure-based Encoder and Pre-training

Zuobai Zhang

Minghao Xu

Aurelie Lozano

Vijil Chenthamarakshan

Payel Das

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.

2023-03-06

ICLR.cc/2023/Workshop/MLDD (poster)

EurNet: Efficient Multi-Range Relational Modeling of Protein Structure

Minghao Xu

Yuanfan Guo

Yi Xu

Xinlei Chen

Yuandong Tian

Modeling the 3D structures of proteins is critical for obtaining effective protein structure representations, which further boosts protein f… (see more)unction understanding. Existing protein structure encoders mainly focus on modeling short-range interactions within protein structures, while they neglect modeling the interactions at multiple length scales that are actually complete interactive patterns in protein structures. To attain complete interaction modeling with efficient computation, we introduce the EurNet for Efficient multi-range relational modeling. In EurNet, we represent the protein structure as a multi-relational residue-level graph with different types of edges for modeling short-range, medium-range and long-range interactions. To efficiently process these different interactive relations, we propose a novel modeling layer, called Gated Relational Message Passing (GRMP), as the basic building block of EurNet. GRMP can capture multiple interactive relations in protein structures with little extra computational cost. We verify the state-of-the-art performance of EurNet on EC and GO protein function prediction benchmarks, and the proposed GRMP layer is proved to achieve better efficiency-performance trade-off than the widely-used relational graph convolution.

2023-03-06

ICLR.cc/2023/Workshop/MLDD (poster)

Privacy-Preserving Fair Item Ranking

Jiajun Sun

Sikha Pentyala

Martine De Cock

Golnoosh Farnadi

Users worldwide access massive amounts of curated data in the form of rankings on a daily basis. The societal impact of this ease of access … (see more)has been studied and work has been done to propose and enforce various notions of fairness in rankings. Current computational methods for fair item ranking rely on disclosing user data to a centralized server, which gives rise to privacy concerns for the users. This work is the first to advance research at the conjunction of producer (item) fairness and consumer (user) privacy in rankings by exploring the incorporation of privacy-preserving techniques; specifically, differential privacy and secure multi-party computation. Our work extends the equity of amortized attention ranking mechanism to be privacy-preserving, and we evaluate its effects with respect to privacy, fairness, and ranking quality. Our results using real-world datasets show that we are able to effectively preserve the privacy of users and mitigate unfairness of items without making additional sacrifices to the quality of rankings in comparison to the ranking mechanism in the clear.

2023-03-06

ArXiv (preprint)

Relationship between prediction accuracy and feature importance reliability: An empirical and theoretical study

Jianzhong Chen

L.Q.R. Ooi

Trevor Wei Kiat Tan

Shaoshi Zhang

Jingwei Li

Christopher L. Asplund

Simon B. Eickhoff

Danilo Bzdok

Avram  j. Holmes

Bt Thomas Yeo

2023-03-06

NeuroImage (published)

Relationship between prediction accuracy and feature importance reliability: An empirical and theoretical study

Jianzhong Chen

L.Q.R. Ooi

Leon Qi Rong Ooi

Trevor Wei Kiat Tan

Shaoshi Zhang

Jingwei Li

Christopher L. Asplund

Simon B. Eickhoff

Danilo Bzdok

Avram J. Holmes

B.T. Thomas Yeo

2023-03-06

NeuroImage (published)

Task-Agnostic Graph Neural Network Evaluation via Adversarial Collaboration

Xiangyu Zhao

Hannes Stärk

Dominique Beaini

Yiren Zhao

Pietro Lio

2023-03-06

ICLR.cc/2023/Workshop/MLDD (poster)

Improved Robustness Against Adaptive Attacks With Ensembles and Error-Correcting Output Codes

Thomas Philippon

Christian Gagné

Neural network ensembles have been studied extensively in the context of adversarial robustness and most ensemble-based approaches remain vu… (see more)lnerable to adaptive attacks. In this paper, we investigate the robustness of Error-Correcting Output Codes (ECOC) ensembles through architectural improvements and ensemble diversity promotion. We perform a comprehensive robustness assessment against adaptive attacks and investigate the relationship between ensemble diversity and robustness. Our results demonstrate the benefits of ECOC ensembles for adversarial robustness compared to regular ensembles of convolutional neural networks (CNNs) and show why the robustness of previous implementations is limited. We also propose an adversarial training method specific to ECOC ensembles that allows to further improve robustness to adaptive attacks.

2023-03-04

ArXiv (preprint)