Quantum Computing-Enhanced Algorithm Unveils Novel Inhibitors for KRAS

The discovery of small molecules with therapeutic potential is a long-standing challenge in chemistry and biology. Researchers have increasingly leveraged novel computational techniques to streamline the drug development process to increase hit rates and reduce the costs associated with bringing a drug to market. To this end, we introduce a quantum-classical generative model that seamlessly integrates the computational power of quantum algorithms trained on a 16-qubit IBM quantum computer with the established reliability of classical methods for designing small molecules. Our hybrid generative model was applied to designing new KRAS inhibitors, a crucial target in cancer therapy. We synthesized 15 promising molecules during our investigation and subjected them to experimental testing to assess their ability to engage with the target. Notably, among these candidates, two molecules, ISM061-018-2 and ISM061-22, each featuring unique scaffolds, stood out by demonstrating effective engagement with KRAS. ISM061-018-2 was identified as a broad-spectrum KRAS inhibitor, exhibiting a binding affinity to KRAS-G12D at $1.4 \mu M$. Concurrently, ISM061-22 exhibited specific mutant selectivity, displaying heightened activity against KRAS G12R and Q61H mutants. To our knowledge, this work shows for the first time the use of a quantum-generative model to yield experimentally confirmed biological hits, showcasing the practical potential of quantum-assisted drug discovery to produce viable therapeutics. Moreover, our findings reveal that the efficacy of distribution learning correlates with the number of qubits utilized, underlining the scalability potential of quantum computing resources. Overall, we anticipate our results to be a stepping stone towards developing more advanced quantum generative models in drug discovery.

Context-Former: Stitching via Latent Conditioned Sequence Modeling

Offline reinforcement learning (RL) algorithms can improve the decision making via stitching sub-optimal trajectories to obtain more optimal ones. This capability is a crucial factor in enabling RL to learn policies that are superior to the behavioral policy. On the other hand, Decision Transformer (DT) abstracts the decision-making as sequence modeling, showcasing competitive performance on offline RL benchmarks, however, recent studies demonstrate that DT lacks of stitching capability, thus exploit stitching capability for DT is vital to further improve its performance. In order to endow stitching capability to DT, we abstract trajectory stitching as expert matching and introduce our approach, ContextFormer, which integrates contextual information-based imitation learning (IL) and sequence modeling to stitch sub-optimal trajectory fragments by emulating the representations of a limited number of expert trajectories. To validate our claim, we conduct experiments from two perspectives: 1) We conduct extensive experiments on D4RL benchmarks under the settings of IL, and experimental results demonstrate ContextFormer can achieve competitive performance in multi-IL settings. 2) More importantly, we conduct a comparison of ContextFormer with diverse competitive DT variants using identical training datasets. The experimental results unveiled ContextFormer's superiority, as it outperformed all other variants, showcasing its remarkable performance.

Deep Dict: Deep Learning-based Lossy Time Series Compressor for IoT Data

We propose Deep Dict, a deep learning-based lossy time series compressor designed to achieve a high compression ratio while maintaining decompression error within a predefined range. Deep Dict incorporates two essential components: the Bernoulli transformer autoencoder (BTAE) and a distortion constraint. BTAE extracts Bernoulli representations from time series data, reducing the size of the representations compared to conventional autoencoders. The distortion constraint limits the prediction error of BTAE to the desired range. Moreover, in order to address the limitations of common regression losses such as L1/L2, we introduce a novel loss function called quantized entropy loss (QEL). QEL takes into account the specific characteristics of the problem, enhancing robustness to outliers and alleviating optimization challenges. Our evaluation of Deep Dict across ten diverse time series datasets from various domains reveals that Deep Dict outperforms state-of-the-art lossy compressors in terms of compression ratio by a significant margin by up to 53.66%.

Probing Structured Semantics Understanding and Generation of Language Models via Question Answering

Recent advancement in the capabilities of large language models (LLMs) has triggered a new surge in LLMs' evaluation. Most recent evaluation works tends to evaluate the comprehensive ability of LLMs over series of tasks. However, the deep structure understanding of natural language is rarely explored. In this work, we examine the ability of LLMs to deal with structured semantics on the tasks of question answering with the help of the human-constructed formal language. Specifically, we implement the inter-conversion of natural and formal language through in-context learning of LLMs to verify their ability to understand and generate the structured logical forms. Extensive experiments with models of different sizes and in different formal languages show that today's state-of-the-art LLMs' understanding of the logical forms can approach human level overall, but there still are plenty of room in generating correct logical forms, which suggest that it is more effective to use LLMs to generate more natural language training data to reinforce a small model than directly answering questions with LLMs. Moreover, our results also indicate that models exhibit considerable sensitivity to different formal languages. In general, the formal language with the lower the formalization level, i.e. the more similar it is to natural language, is more LLMs-friendly.

Adaptive Proximal Policy Optimization with Upper Confidence Bound

Trust Region Policy Optimization (TRPO) attractively optimizes the policy while constraining the update of the new policy within a trust region, ensuring the stability and monotonic optimization. Building on the theoretical guarantees of trust region optimization, Proximal Policy Optimization (PPO) successfully enhances the algorithm's sample efficiency and reduces deployment complexity by confining the update of the new and old policies within a surrogate trust region. However, this approach is limited by the fixed setting of surrogate trust region and is not sufficiently adaptive, because there is no theoretical proof that the optimal clipping bound remains consistent throughout the entire training process, truncating the ratio of the new and old policies within surrogate trust region can ensure that the algorithm achieves its best performance, therefore, exploring and researching a dynamic clip bound for improving PPO's performance can be quite beneficial. To design an adaptive clipped trust region and explore the dynamic clip bound's impact on the performance of PPO, we introduce an adaptive PPO-CLIP (Adaptive-PPO) method that dynamically explores and exploits the clip bound using a bandit during the online training process. Furthermore, ample experiments will initially demonstrate that our Adaptive-PPO exhibits sample efficiency and performance compared to PPO-CLIP.

Offline Imitation Learning with Variational Counterfactual Reasoning

In offline Imitation Learning (IL), an agent aims to learn an optimal expert behavior policy without additional online environment interactions. However, in many real-world scenarios, such as robotics manipulation, the offline dataset is collected from suboptimal behaviors without rewards. Due to the scarce expert data, the agents usually suffer from simply memorizing poor trajectories and are vulnerable to the variations in the environments, lacking the capability of generalizing to new environments. To effectively remove spurious features that would otherwise bias the agent and hinder generalization, we propose a framework named \underline{O}ffline \underline{I}mitation \underline{L}earning with \underline{C}ounterfactual data \underline{A}ugmentation (OILCA). In particular, we leverage the identifiable variational autoencoder to generate \textit{counterfactual} samples. We theoretically analyze the counterfactual identification and the improvement of generalization. Moreover, we conduct extensive experiments to demonstrate that our approach significantly outperforms various baselines on both \textsc{DeepMind Control Suite} benchmark for in-distribution robustness and \textsc{CausalWorld} benchmark for out-of-distribution generalization.

Multidomain transformer-based deep learning for early detection of network intrusion

Timely response of Network Intrusion Detection Systems (NIDS) is constrained by the flow generation process which requires accumulation of network packets. This paper introduces Multivariate Time Series (MTS) early detection into NIDS to identify malicious flows prior to their arrival at target systems. With this in mind, we first propose a novel feature extractor, Time Series Network Flow Meter (TS-NFM), that represents network flow as MTS with explainable features, and a new benchmark dataset is created using TS-NFM and the meta-data of CICIDS2017, called SCVIC-TS-2022. Additionally, a new deep learning-based early detection model called Multi-Domain Transformer (MDT) is proposed, which incorporates the frequency domain into Transformer. This work further proposes a Multi-Domain Multi-Head Attention (MD-MHA) mechanism to improve the ability of MDT to extract better features. Based on the experimental results, the proposed methodology improves the earliness of the conventional NIDS (i.e., percentage of packets that are used for classification) by 5x10^4 times and duration-based earliness (i.e., percentage of duration of the classified packets of a flow) by a factor of 60, resulting in a 84.1% macro F1 score (31% higher than Transformer) on SCVIC-TS-2022. Additionally, the proposed MDT outperforms the state-of-the-art early detection methods by 5% and 6% on ECG and Wafer datasets, respectively.

STRAPPER: Preference-based Reinforcement Learning via Self-training Augmentation and Peer Regularization

Preference-based reinforcement learning (PbRL) promises to learn a complex reward function with binary human preference. However, such human-in-the-loop formulation requires considerable human effort to assign preference labels to segment pairs, hindering its large-scale applications. Recent approache has tried to reuse unlabeled segments, which implicitly elucidates the distribution of segments and thereby alleviates the human effort. And consistency regularization is further considered to improve the performance of semi-supervised learning. However, we notice that, unlike general classification tasks, in PbRL there exits a unique phenomenon that we defined as similarity trap in this paper. Intuitively, human can have diametrically opposite preferredness for similar segment pairs, but such similarity may trap consistency regularization fail in PbRL. Due to the existence of similarity trap, such consistency regularization improperly enhances the consistency possiblity of the model's predictions between segment pairs, and thus reduces the confidence in reward learning, since the augmented distribution does not match with the original one in PbRL. To overcome such issue, we present a self-training method along with our proposed peer regularization, which penalizes the reward model memorizing uninformative labels and acquires confident predictions. Empirically, we demonstrate that our approach is capable of learning well a variety of locomotion and robotic manipulation behaviors using different semi-supervised alternatives and peer regularization.

Design from Policies: Conservative Test-Time Adaptation for Offline Policy Optimization

In this work, we decouple the iterative bi-level offline RL from the offline training phase, forming a non-iterative bi-level paradigm and avoiding the iterative error propagation over two levels. Specifically, this non-iterative paradigm allows us to conduct inner-level optimization in training (for OOD issues), while performing outer-level optimization in testing (for reward maximizing). Naturally, such a paradigm raises three core questions that are \textit{not} fully answered by prior non-iterative offline RL counterparts like reward-conditioned policy: Q1) What information should we transfer from the inner-level to the outer-level? Q2) What should we pay attention to when exploiting the transferred information in the outer-level optimization? Q3) What are the~benefits of concurrently conducting outer-level optimization during testing? Motivated by model-based optimization~{(MBO)}, we propose DROP (\textbf{D}esign f\textbf{RO}m \textbf{P}olicies), which fully answers the above questions. Specifically, in the inner-level, DROP decomposes offline data into multiple subsets and learns an {MBO} score model~(A1). To keep safe exploitation to the score model in the outer-level, we explicitly learn a behavior embedding and introduce a conservative regularization (A2). During testing, we show that DROP permits test-time adaptation, enabling an adaptive inference across states~(A3). Empirically, we find that DROP, compared to prior non-iterative offline RL counterparts, gains an average improvement probability of more than 80\%, and achieves comparable or better performance compared to prior iterative baselines.

ChiPFormer: Transferable Chip Placement via Offline Decision Transformer

Placement is a critical step in modern chip design, aiming to determine the positions of circuit modules on the chip canvas. Recent works have shown that reinforcement learning (RL) can improve human performance in chip placement. However, such an RL-based approach suffers from long training time and low transfer ability in unseen chip circuits. To resolve these challenges, we cast the chip placement as an offline RL formulation and present ChiPFormer that enables learning a transferable placement policy from fixed offline data. ChiPFormer has several advantages that prior arts do not have. First, ChiPFormer can exploit offline placement designs to learn transferable policies more efficiently in a multi-task setting. Second, ChiPFormer can promote effective finetuning for unseen chip circuits, reducing the placement runtime from hours to minutes. Third, extensive experiments on 32 chip circuits demonstrate that ChiPFormer achieves significantly better placement quality while reducing the runtime by 10x compared to recent state-of-the-art approaches in both public benchmarks and realistic industrial tasks. The deliverables are released at https://sites.google.com/view/chipformer/home.