Aurelie Lozano

Zuobai Zhang, Minghao Xu, Arian Jamasb et al.

Learning effective protein representations is critical in a variety of tasks in biology such as predicting protein function or structure. Existing approaches usually pretrain protein language models on a large number of unlabeled amino acid sequences and then finetune the models with some labeled data in downstream tasks. Despite the effectiveness of sequence-based approaches, the power of pretraining on known protein structures, which are available in smaller numbers only, has not been explored for protein property prediction, though protein structures are known to be determinants of protein function. In this paper, we propose to pretrain protein representations according to their 3D structures. We first present a simple yet effective encoder to learn the geometric features of a protein. We pretrain the protein graph encoder by leveraging multiview contrastive learning and different self-prediction tasks. Experimental results on both function prediction and fold classification tasks show that our proposed pretraining methods outperform or are on par with the state-of-the-art sequence-based methods, while using much less pretraining data. Our implementation is available at https://github.com/DeepGraphLearning/GearNet.

Igor Melnyk, Aurelie Lozano, Payel Das et al.

Inverse protein folding, the process of designing sequences that fold into a specific 3D structure, is crucial in bio-engineering and drug discovery. Traditional methods rely on experimentally resolved structures, but these cover only a small fraction of protein sequences. Forward folding models like AlphaFold offer a potential solution by accurately predicting structures from sequences. However, these models are too slow for integration into the optimization loop of inverse folding models during training. To address this, we propose using knowledge distillation on folding model confidence metrics, such as pTM or pLDDT scores, to create a faster and end-to-end differentiable distilled model. This model can then be used as a structure consistency regularizer in training the inverse folding model. Our technique is versatile and can be applied to other design tasks, such as sequence-based protein infilling. Experimental results show that our method outperforms non-regularized baselines, yielding up to 3% improvement in sequence recovery and up to 45% improvement in protein diversity while maintaining structural consistency in generated sequences. Code is available at https://github.com/IBM/AFDistill

Xi Yang, Aurelie Lozano, Naoki Abe et al.

Despite rapid progress in AI agents for enterprise automation and decision-making, their real-world deployment and further performance gains remain constrained by limited data quality and quantity, complex real-world reasoning demands, difficulties with self-play, and the lack of reliable feedback signals. To address these challenges, we propose a lightweight, model-agnostic framework for improving LLM-based enterprise agents via offline reinforcement learning (RL). The proposed Context Engineering via DT-MDP (DT-MDP-CE) framework comprises three key components: (1) A Digital-Twin Markov Decision Process (DT-MDP), which abstracts the agent's reasoning behavior as a finite MDP; (2) A robust contrastive inverse RL, which, armed with the DT-MDP, to efficiently estimate a well-founded reward function and induces policies from mixed-quality offline trajectories; and (3) RL-guided context engineering, which uses the policy obtained from the integrated process of (1) and (2), to improve the agent's decision-making behavior. As a case study, we apply the framework to a representative task in the enterprise-oriented domain of IT automation. Extensive experimental results demonstrate consistent and significant improvements over baseline agents across a wide range of evaluation settings, suggesting that the framework can generalize to other agents sharing similar characteristics in enterprise environments.

Amit Dhurandhar, Tejaswini Pedapati, Ronny Luss et al.

Transformer-based Language Models have become ubiquitous in Natural Language Processing (NLP) due to their impressive performance on various tasks. However, expensive training as well as inference remains a significant impediment to their widespread applicability. While enforcing sparsity at various levels of the model architecture has found promise in addressing scaling and efficiency issues, there remains a disconnect between how sparsity affects network topology. Inspired by brain neuronal networks, we explore sparsity approaches through the lens of network topology. Specifically, we exploit mechanisms seen in biological networks, such as preferential attachment and redundant synapse pruning, and show that principled, model-agnostic sparsity approaches are performant and efficient across diverse NLP tasks, spanning both classification (such as natural language inference) and generation (summarization, machine translation), despite our sole objective not being optimizing performance. NeuroPrune is competitive with (or sometimes superior to) baselines on performance and can be up to $10$x faster in terms of training time for a given level of sparsity, simultaneously exhibiting measurable improvements in inference time in many cases.

Payel Das, Ching-Yun Ko, Sihui Dai et al.

Large language models often expose their brittleness in reasoning tasks, especially while executing long chains of reasoning over context. We propose MemReasoner, a new and simple memory-augmented LLM architecture, in which the memory learns the relative order of facts in context, and enables hopping over them, while the decoder selectively attends to the memory. MemReasoner is trained end-to-end, with optional supporting fact supervision of varying degrees. We train MemReasoner, along with existing memory-augmented transformer models and a state-space model, on two distinct synthetic multi-hop reasoning tasks. Experiments performed under a variety of challenging scenarios, including the presence of long distractor text or target answer changes in test set, show strong generalization of MemReasoner on both single- and two-hop tasks. This generalization of MemReasoner is achieved using none-to-weak supporting fact supervision (using none and 1\% of supporting facts for one- and two-hop tasks, respectively). In contrast, baseline models overall struggle to generalize and benefit far less from using full supporting fact supervision. The results highlight the importance of explicit memory mechanisms, combined with additional weak supervision, for improving large language model's context processing ability toward reasoning tasks.

Igor Melnyk, Payel Das, Vijil Chenthamarakshan et al.

Computational protein design, i.e. inferring novel and diverse protein sequences consistent with a given structure, remains a major unsolved challenge. Recently, deep generative models that learn from sequences alone or from sequences and structures jointly have shown impressive performance on this task. However, those models appear limited in terms of modeling structural constraints, capturing enough sequence diversity, or both. Here we consider three recently proposed deep generative frameworks for protein design: (AR) the sequence-based autoregressive generative model, (GVP) the precise structure-based graph neural network, and Fold2Seq that leverages a fuzzy and scale-free representation of a three-dimensional fold, while enforcing structure-to-sequence (and vice versa) consistency. We benchmark these models on the task of computational design of antibody sequences, which demand designing sequences with high diversity for functional implication. The Fold2Seq framework outperforms the two other baselines in terms of diversity of the designed sequences, while maintaining the typical fold.

Tsui-Wei Weng, Huan Zhang, Pin-Yu Chen et al.

CLEVER (Cross-Lipschitz Extreme Value for nEtwork Robustness) is an Extreme Value Theory (EVT) based robustness score for large-scale deep neural networks (DNNs). In this paper, we propose two extensions on this robustness score. First, we provide a new formal robustness guarantee for classifier functions that are twice differentiable. We apply extreme value theory on the new formal robustness guarantee and the estimated robustness is called second-order CLEVER score. Second, we discuss how to handle gradient masking, a common defensive technique, using CLEVER with Backward Pass Differentiable Approximation (BPDA). With BPDA applied, CLEVER can evaluate the intrinsic robustness of neural networks of a broader class -- networks with non-differentiable input transformations. We demonstrate the effectiveness of CLEVER with BPDA in experiments on a 121-layer Densenet model trained on the ImageNet dataset.

Sahil Garg, Irina Rish, Guillermo Cecchi et al.

In this paper, we focus on online representation learning in non-stationary environments which may require continuous adaptation of model architecture. We propose a novel online dictionary-learning (sparse-coding) framework which incorporates the addition and deletion of hidden units (dictionary elements), and is inspired by the adult neurogenesis phenomenon in the dentate gyrus of the hippocampus, known to be associated with improved cognitive function and adaptation to new environments. In the online learning setting, where new input instances arrive sequentially in batches, the neuronal-birth is implemented by adding new units with random initial weights (random dictionary elements); the number of new units is determined by the current performance (representation error) of the dictionary, higher error causing an increase in the birth rate. Neuronal-death is implemented by imposing l1/l2-regularization (group sparsity) on the dictionary within the block-coordinate descent optimization at each iteration of our online alternating minimization scheme, which iterates between the code and dictionary updates. Finally, hidden unit connectivity adaptation is facilitated by introducing sparsity in dictionary elements. Our empirical evaluation on several real-life datasets (images and language) as well as on synthetic data demonstrates that the proposed approach can considerably outperform the state-of-art fixed-size (nonadaptive) online sparse coding of Mairal et al. (2009) in the presence of nonstationary data. Moreover, we identify certain properties of the data (e.g., sparse inputs with nearly non-overlapping supports) and of the model (e.g., dictionary sparsity) associated with such improvements.

Eunho Yang, Aurelie Lozano, Aleksandr Aravkin

We consider the problem of robustifying high-dimensional structured estimation. Robust techniques are key in real-world applications which often involve outliers and data corruption. We focus on trimmed versions of structurally regularized M-estimators in the high-dimensional setting, including the popular Least Trimmed Squares estimator, as well as analogous estimators for generalized linear models and graphical models, using possibly non-convex loss functions. We present a general analysis of their statistical convergence rates and consistency, and then take a closer look at the trimmed versions of the Lasso and Graphical Lasso estimators as special cases. On the optimization side, we show how to extend algorithms for M-estimators to fit trimmed variants and provide guarantees on their numerical convergence. The generality and competitive performance of high-dimensional trimmed estimators are illustrated numerically on both simulated and real-world genomics data.

Vikas Sindhwani, Ha Quang Minh, Aurelie Lozano

We propose a general matrix-valued multiple kernel learning framework for high-dimensional nonlinear multivariate regression problems. This framework allows a broad class of mixed norm regularizers, including those that induce sparsity, to be imposed on a dictionary of vector-valued Reproducing Kernel Hilbert Spaces. We develop a highly scalable and eigendecomposition-free algorithm that orchestrates two inexact solvers for simultaneously learning both the input and output components of separable matrix-valued kernels. As a key application enabled by our framework, we show how high-dimensional causal inference tasks can be naturally cast as sparse function estimation problems, leading to novel nonlinear extensions of a class of Graphical Granger Causality techniques. Our algorithmic developments and extensive empirical studies are complemented by theoretical analyses in terms of Rademacher generalization bounds.