Tong Lin

Tong Lin, Sijie Chen, Ruchira Basu et al.

Despite the prevalence and many successes of deep learning applications in de novo molecular design, the problem of peptide generation targeting specific proteins remains unsolved. A main barrier for this is the scarcity of the high-quality training data. To tackle the issue, we propose a novel machine learning based peptide design architecture, called Latent Space Approximate Trajectory Collector (LSATC). It consists of a series of samplers on an optimization trajectory on a highly non-convex energy landscape that approximates the distributions of peptides with desired properties in a latent space. The process involves little human intervention and can be implemented in an end-to-end manner. We demonstrate the model by the design of peptide extensions targeting Beta-catenin, a key nuclear effector protein involved in canonical Wnt signalling. When compared with a random sampler, LSATC can sample peptides with $36\%$ lower binding scores in a $16$ times smaller interquartile range (IQR) and $284\%$ less hydrophobicity with a $1.4$ times smaller IQR. LSATC also largely outperforms other common generative models. Finally, we utilized a clustering algorithm to select 4 peptides from the 100 LSATC designed peptides for experimental validation. The result confirms that all the four peptides extended by LSATC show improved Beta-catenin binding by at least $20.0\%$, and two of the peptides show a $3$ fold increase in binding affinity as compared to the base peptide.

Xiaohan Zou, Tong Lin

Continual learning aims to alleviate catastrophic forgetting when handling consecutive tasks under non-stationary distributions. Gradient-based meta-learning algorithms have shown the capability to implicitly solve the transfer-interference trade-off problem between different examples. However, they still suffer from the catastrophic forgetting problem in the setting of continual learning, since the past data of previous tasks are no longer available. In this work, we propose a novel efficient meta-learning algorithm for solving the online continual learning problem, where the regularization terms and learning rates are adapted to the Taylor approximation of the parameter's importance to mitigate forgetting. The proposed method expresses the gradient of the meta-loss in closed-form and thus avoid computing second-order derivative which is computationally inhibitable. We also use Proximal Gradient Descent to further improve computational efficiency and accuracy. Experiments on diverse benchmarks show that our method achieves better or on-par performance and much higher efficiency compared to the state-of-the-art approaches.

Shijie Fang, Qianhan Feng, Tong Lin

Despite the progress of Semi-supervised Learning (SSL), existing methods fail to utilize unlabeled data effectively and efficiently. Many pseudo-label-based methods select unlabeled examples based on inaccurate confidence scores from the classifier. Most prior work also uses all available unlabeled data without pruning, making it difficult to handle large amounts of unlabeled data. To address these issues, we propose two methods: Variational Confidence Calibration (VCC) and Influence-Function-based Unlabeled Sample Elimination (INFUSE). VCC is an universal plugin for SSL confidence calibration, using a variational autoencoder to select more accurate pseudo labels based on three types of consistency scores. INFUSE is a data pruning method that constructs a core dataset of unlabeled examples under SSL. Our methods are effective in multiple datasets and settings, reducing classification errors rates and saving training time. Together, VCC-INFUSE reduces the error rate of FlexMatch on the CIFAR-100 dataset by 1.08% while saving nearly half of the training time.