Deng Pan

Kehan Wu, Yingce Xia, Yang Fan et al. · microsoft-research

Structure-based drug design is drawing growing attentions in computer-aided drug discovery. Compared with the virtual screening approach where a pre-defined library of compounds are computationally screened, de novo drug design based on the structure of a target protein can provide novel drug candidates. In this paper, we present a generative solution named TamGent (Target-aware molecule generator with Transformer) that can directly generate candidate drugs from scratch for a given target, overcoming the limits imposed by existing compound libraries. Following the Transformer framework (a state-of-the-art framework in deep learning), we design a variant of Transformer encoder to process 3D geometric information of targets and pre-train the Transformer decoder on 10 million compounds from PubChem for candidate drug generation. Systematical evaluation on candidate compounds generated for targets from DrugBank shows that both binding affinity and drugability are largely improved. TamGent outperforms previous baselines in terms of both effectiveness and efficiency. The method is further verified by generating candidate compounds for the SARS-CoV-2 main protease and the oncogenic mutant KRAS G12C. The results show that our method not only re-discovers previously verified drug molecules , but also generates novel molecules with better docking scores, expanding the compound pool and potentially leading to the discovery of novel drugs.

Shixiao Fan, Xuan Cheng, Xiaomin Wang et al. · gatech

Recently, researchers have shown an increased interest in the online knowledge distillation. Adopting an one-stage and end-to-end training fashion, online knowledge distillation uses aggregated intermediated predictions of multiple peer models for training. However, the absence of a powerful teacher model may result in the homogeneity problem between group peers, affecting the effectiveness of group distillation adversely. In this paper, we propose a novel online knowledge distillation method, \textbf{C}hannel \textbf{S}elf-\textbf{S}upervision for Online Knowledge Distillation (CSS), which structures diversity in terms of input, target, and network to alleviate the homogenization problem. Specifically, we construct a dual-network multi-branch structure and enhance inter-branch diversity through self-supervised learning, adopting the feature-level transformation and augmenting the corresponding labels. Meanwhile, the dual network structure has a larger space of independent parameters to resist the homogenization problem during distillation. Extensive quantitative experiments on CIFAR-100 illustrate that our method provides greater diversity than OKDDip and we also give pretty performance improvement, even over the state-of-the-art such as PCL. The results on three fine-grained datasets (StanfordDogs, StanfordCars, CUB-200-211) also show the significant generalization capability of our approach.

Deng Pan, Mohammad Ali Khoshkholghi, Toktam Mahmoodi

Unmanned aerial vehicles (UAV) or drones play many roles in a modern smart city such as the delivery of goods, mapping real-time road traffic and monitoring pollution. The ability of drones to perform these functions often requires the support of machine learning technology. However, traditional machine learning models for drones encounter data privacy problems, communication costs and energy limitations. Federated Learning, an emerging distributed machine learning approach, is an excellent solution to address these issues. Federated learning (FL) allows drones to train local models without transmitting raw data. However, existing FL requires a central server to aggregate the trained model parameters of the UAV. A failure of the central server can significantly impact the overall training. In this paper, we propose two aggregation methods: Commutative FL and Alternate FL, based on the existing architecture of decentralised Federated Learning for UAV Networks (DFL-UN) by adding a unique aggregation method of decentralised FL. Those two methods can effectively control energy consumption and communication cost by controlling the number of local training epochs, local communication, and global communication. The simulation results of the proposed training methods are also presented to verify the feasibility and efficiency of the architecture compared with two benchmark methods (e.g. standard machine learning training and standard single aggregation server training). The simulation results show that the proposed methods outperform the benchmark methods in terms of operational stability, energy consumption and communication cost.

Xin Li, Xiangrui Li, Deng Pan et al.

Deep neural networks (DNNs) for supervised learning can be viewed as a pipeline of the feature extractor (i.e., last hidden layer) and a linear classifier (i.e., output layer) that are trained jointly with stochastic gradient descent (SGD) on the loss function (e.g., cross-entropy). In each epoch, the true gradient of the loss function is estimated using a mini-batch sampled from the training set and model parameters are then updated with the mini-batch gradients. Although the latter provides an unbiased estimation of the former, they are subject to substantial variances derived from the size and number of sampled mini-batches, leading to noisy and jumpy updates. To stabilize such undesirable variance in estimating the true gradients, we propose In-Training Representation Alignment (ITRA) that explicitly aligns feature distributions of two different mini-batches with a matching loss in the SGD training process. We also provide a rigorous analysis of the desirable effects of the matching loss on feature representation learning: (1) extracting compact feature representation; (2) reducing over-adaption on mini-batches via an adaptive weighting mechanism; and (3) accommodating to multi-modalities. Finally, we conduct large-scale experiments on both image and text classifications to demonstrate its superior performance to the strong baselines.

Mingqian Ma, Guoqing Liu, Chuan Cao et al. · microsoft-research

Advances in natural language processing and large language models have sparked growing interest in modeling DNA, often referred to as the "language of life". However, DNA modeling poses unique challenges. First, it requires the ability to process ultra-long DNA sequences while preserving single-nucleotide resolution, as individual nucleotides play a critical role in DNA function. Second, success in this domain requires excelling at both generative and understanding tasks: generative tasks hold potential for therapeutic and industrial applications, while understanding tasks provide crucial insights into biological mechanisms and diseases. To address these challenges, we propose HybriDNA, a decoder-only DNA language model that incorporates a hybrid Transformer-Mamba2 architecture, seamlessly integrating the strengths of attention mechanisms with selective state-space models. This hybrid design enables HybriDNA to efficiently process DNA sequences up to 131kb in length with single-nucleotide resolution. HybriDNA achieves state-of-the-art performance across 33 DNA understanding datasets curated from the BEND, GUE, and LRB benchmarks, and demonstrates exceptional capability in generating synthetic cis-regulatory elements (CREs) with desired properties. Furthermore, we show that HybriDNA adheres to expected scaling laws, with performance improving consistently as the model scales from 300M to 3B and 7B parameters. These findings underscore HybriDNA's versatility and its potential to advance DNA research and applications, paving the way for innovations in understanding and engineering the "language of life".