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1. End-to-end sequence-structure-function meta-learning predicts genome-wide chemical-protein interactions for dark proteins

   https://doi.org/10.1371/journal.pcbi.1010851  

   Cai, Tian ; Xie, Li ; Zhang, Shuo ; Chen, Muge ; He, Di ; Badkul, Amitesh ; Liu, Yang ; Namballa, Hari Krishna ; Dorogan, Michael ; Harding, Wayne W. ; et al ( January 2023 , PLOS Computational Biology)

   Skolnick, Jeffrey (Ed.)

   Systematically discovering protein-ligand interactions across the entire human and pathogen genomes is critical in chemical genomics, protein function prediction, drug discovery, and many other areas. However, more than 90% of gene families remain “dark”—i.e., their small-molecule ligands are undiscovered due to experimental limitations or human/historical biases. Existing computational approaches typically fail when the dark protein differs from those with known ligands. To address this challenge, we have developed a deep learning framework, called PortalCG, which consists of four novel components: (i) a 3-dimensional ligand binding site enhanced sequence pre-training strategy to encode the evolutionary links between ligand-binding sites across gene families; (ii) an end-to-end pretraining-fine-tuning strategy to reduce the impact of inaccuracy of predicted structures on function predictions by recognizing the sequence-structure-function paradigm; (iii) a new out-of-cluster meta-learning algorithm that extracts and accumulates information learned from predicting ligands of distinct gene families (meta-data) and applies the meta-data to a dark gene family; and (iv) a stress model selection step, using different gene families in the test data from those in the training and development data sets to facilitate model deployment in a real-world scenario. In extensive and rigorous benchmark experiments, PortalCG considerably outperformed state-of-the-art techniques of machine learning and protein-ligand docking when applied to dark gene families, and demonstrated its generalization power for target identifications and compound screenings under out-of-distribution (OOD) scenarios. Furthermore, in an external validation for the multi-target compound screening, the performance of PortalCG surpassed the rational design from medicinal chemists. Our results also suggest that a differentiable sequence-structure-function deep learning framework, where protein structural information serves as an intermediate layer, could be superior to conventional methodology where predicted protein structures were used for the compound screening. We applied PortalCG to two case studies to exemplify its potential in drug discovery: designing selective dual-antagonists of dopamine receptors for the treatment of opioid use disorder (OUD), and illuminating the understudied human genome for target diseases that do not yet have effective and safe therapeutics. Our results suggested that PortalCG is a viable solution to the OOD problem in exploring understudied regions of protein functional space. 

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2. Exploiting Federated Learning Technique to Recognize Human Activities in Resource-Constrained Environment

   Ahmed Imteaj, Raghad Alabagi ( December 2021 , The 13th International Conference on Intelligent Human Computer Interaction (IHCI-2021))

   The conventional machine learning (ML) and deep learning (DL) methods use large amount of data to construct desirable prediction models in a central fusion center for recognizing human activities. However, such model training encounters high communication costs and leads to privacy infringement. To address the issues of high communication overhead and privacy leakage, we employed a widely popular distributed ML technique called Federated Learning (FL) that generates a global model for predicting human activities by combining participated agents’ local knowledge. The state-of-the-art FL model fails to maintain acceptable accuracy when there is a large number of unreliable agents who can infuse false model, or, resource-constrained agents that fails to perform an assigned computational task within a given time window. We developed an FL model for predicting human activities by monitoring agent’s contributions towards model convergence and avoiding the unreliable and resource-constrained agents from training. We assign a score to each client when it joins in a network and the score is updated based on the agent’s activities during training. We consider three mobile robots as FL clients that are heterogeneous in terms of their resources such as processing capability, memory, bandwidth, battery-life and data volume. We consider heterogeneous mobile robots for understanding the effects of real-world FL setting in presence of resource-constrained agents. We consider an agent unreliable if it repeatedly gives slow response or infuses incorrect models during training. By disregarding the unreliable and weak agents, we carry-out the local training of the FL process on selected agents. If somehow, a weak agent is selected and started showing straggler issues, we leverage asynchronous FL mechanism that aggregate the local models whenever it receives a model update from the agents. Asynchronous FL eliminates the issue of waiting for a long time to receive model updates from the weak agents. To the end, we simulate how we can track the behavior of the agents through a reward-punishment scheme and present the influence of unreliable and resource-constrained agents in the FL process. We found that FL performs slightly worse than centralized models, if there is no unreliable and resource-constrained agent. However, as the number of malicious and straggler clients increases, our proposed model performs more effectively by identifying and avoiding those agents while recognizing human activities as compared to the stateof-the-art FL and ML approaches. 

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3. CAT: Closed-loop Adversarial Training for Safe End-to-End Driving

   Zhang, Linrui ; Peng, Zhenghao ; Li, Quanyi ; Zhou, Bolei. ( November 2023 , Conference on Robot Learning (CoRL) 2023)

   Driving safety is a top priority for autonomous vehicles. Orthogonal to prior work handling accident-prone traffic events by algorithm designs at the policy level, we investigate a Closed-loop Adversarial Training (CAT) framework for safe end-to-end driving in this paper through the lens of environment augmentation. CAT aims to continuously improve the safety of driving agents by training the agent on safety-critical scenarios that are dynamically generated over time. A novel resampling technique is developed to turn log-replay real-world driving scenarios into safety-critical ones via probabilistic factorization, where the adversarial traffic generation is modeled as the multiplication of standard motion prediction sub-problems. Consequently, CAT can launch more efficient physical attacks compared to existing safety-critical scenario generation methods and yields a significantly less computational cost in the iterative learning pipeline. We incorporate CAT into the MetaDrive simulator and validate our approach on hundreds of driving scenarios imported from real-world driving datasets. Experimental results demonstrate that CAT can effectively generate adversarial scenarios countering the agent being trained. After training, the agent can achieve superior driving safety in both log-replay and safety-critical traffic scenarios on the held- out test set. Code and data are available at https://metadriverse.github.io/cat. 

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4. Runtime Monitoring of Deep Neural Networks Using Top-Down Context Models Inspired by Predictive Processing and Dual Process Theory

   Roy, A. ; Cobb, A. ; Bastian, Nathaniel ; Jalaian, Brian ; Jha, Susmit ( April 2022 , AAAI Spring Symposium 2022)

   Deep neural networks (DNNs) have achieved near-human level accuracy on many datasets across different domains. But they are known to produce incorrect predictions with high confidence on inputs far from the training distribution. This challenge of lack of calibration of DNNs has limited the adoption of deep learning models in high-assurance systems such as autonomous driving, air traffic management, cybersecurity, and medical diagnosis. The problem of detecting when an input is outside the training distribution of a machine learning model, and hence, its prediction on this input cannot be trusted, has received significant attention recently. Several techniques based on statistical, geometric, topological, or relational signatures have been developed to detect the out-of-distribution (OOD) or novel inputs. In this paper, we present a runtime monitor based on predictive processing and dual process theory. We posit that the bottom-up deep neural networks can be monitored using top-down context models comprising two layers. The first layer is a feature density model that learns the joint distribution of the original DNN’s inputs, outputs, and the model’s explanation for its decisions. The second layer is a graph Markov neural network that captures an even broader context. We demonstrate the efficacy of our monitoring architecture in recognizing out-of-distribution and out-of-context inputs on the image classification and object detection tasks. 

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5. Interpretable Detection of Distribution Shifts in Learning Enabled Cyber-Physical Systems

   https://doi.org/10.1109/ICCPS54341.2022.00027  

   Yang, Yahan ; Kaur, Ramneet ; Dutta, Suradeep ; Lee, Insup ( May 2022 , ACMIEEE International Conference on CyberPhysical Systems)

   The use of learning based components in cyber-physical systems (CPS) has created a gamut of possible avenues to use high dimensional real world signals generated from sensors like camera and LiDAR. The ability to process such signals can be largely attributed to the adoption of high-capacity function approximators like deep neural networks. However, this does not come without its potential perils. The pitfalls arise from possible over-fitting, and subsequent unsafe behavior when exposed to unknown environments. One challenge is that, in high dimensional input spaces it is almost impossible to experience enough training data in the design phase. What is required here, is an efficient way to flag out-of-distribution (OOD) samples that is precise enough to not raise too many false alarms. In addition, the system needs to be able to detect these in a computationally efficient manner at runtime. In this paper, our proposal is to build good representations for in-distribution data. We introduce the idea of a memory bank to store prototypical samples from the input space. We use these memories to compute probability density estimates using kernel density estimation techniques. We evaluate our technique on two challenging scenarios : a self-driving car setting implemented inside the simulator CARLA with image inputs, and an autonomous racing car navigation setting, with LiDAR inputs. In both settings, it was observed that a deviation from in-distribution setting can potentially lead to deviation from safe behavior. An added benefit of using training samples as memories to detect out-of-distribution inputs is that the system is interpretable to a human operator. Explanation of this nature is generally hard to obtain from pure deep learning based alternatives. Our code for reproducing the experiments is available at https:// github.com/ yangy96/ interpretable_ood_detection.git 

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