NovoBench: Benchmarking Deep Learning-based De Novo Peptide Sequencing Methods in Proteomics

Tandem mass spectrometry has played a pivotal role in advancing proteomics, enabling the high-throughput analysis of protein composition in biological tissues. Many deep learning methods have been developed for \emph{de novo} peptide sequencing task, i.e., predicting the peptide sequence for the observed mass spectrum. However, two key challenges seriously hinder the further advancement of this important task. Firstly, since there is no consensus for the evaluation datasets, the empirical results in different research papers are often not comparable, leading to unfair comparison. Secondly, the current methods are usually limited to amino acid-level or peptide-level precision and recall metrics. In this work, we present the first unified benchmark NovoBench for \emph{de novo} peptide sequencing, which comprises diverse mass spectrum data, integrated models, and comprehensive evaluation metrics. Recent impressive methods, including DeepNovo, PointNovo, Casanovo, InstaNovo, AdaNovo and $\pi$-HelixNovo are integrated into our framework. In addition to amino acid-level and peptide-level precision and recall, we evaluate the models' performance in terms of identifying post-tranlational modifications (PTMs), efficiency and robustness to peptide length, noise peaks and missing fragment ratio, which are important influencing factors while seldom be considered. Leveraging this benchmark, we conduct a large-scale study of current methods, report many insightful findings that open up new possibilities for future development. The benchmark will be open-sourced to facilitate future research and application.

Enabling On-Device Learning via Experience Replay with Efficient Dataset Condensation

Upon deployment to edge devices, it is often desirable for a model to further learn from streaming data to improve accuracy. However, extracting representative features from such data is challenging because it is typically unlabeled, non-independent and identically distributed (non-i.i.d), and is seen only once. To mitigate this issue, a common strategy is to maintain a small data buffer on the edge device to hold the most representative data for further learning. As most data is either never stored or quickly discarded, identifying the most representative data to avoid significant information loss becomes critical. In this paper, we propose an on-device framework that addresses this issue by condensing incoming data into more informative samples. Specifically, to effectively handle unlabeled incoming data, we propose a pseudo-labeling technique designed for unlabeled on-device learning environments. Additionally, we develop a dataset condensation technique that only requires little computation resources. To counteract the effects of noisy labels during the condensation process, we further utilize a contrastive learning objective to improve the purity of class data within the buffer. Our empirical results indicate substantial improvements over existing methods, particularly when buffer capacity is severely restricted. For instance, with a buffer capacity of just one sample per class, our method achieves an accuracy that outperforms the best existing baseline by 58.4% on the CIFAR-10 dataset.

Towards Energy-Aware Federated Learning via MARL: A Dual-Selection Approach for Model and Client

Although Federated Learning (FL) is promising in knowledge sharing for heterogeneous Artificial Intelligence of Thing (AIoT) devices, their training performance and energy efficacy are severely restricted in practical battery-driven scenarios due to the ``wooden barrel effect'' caused by the mismatch between homogeneous model paradigms and heterogeneous device capability. As a result, due to various kinds of differences among devices, it is hard for existing FL methods to conduct training effectively in energy-constrained scenarios, such as the battery constraints of devices. To tackle the above issues, we propose an energy-aware FL framework named DR-FL, which considers the energy constraints in both clients and heterogeneous deep learning models to enable energy-efficient FL. Unlike Vanilla FL, DR-FL adopts our proposed Muti-Agents Reinforcement Learning (MARL)-based dual-selection method, which allows participated devices to make contributions to the global model effectively and adaptively based on their computing capabilities and energy capacities in a MARL-based manner. Experiments on various well-known datasets show that DR-FL can not only maximise knowledge sharing among heterogeneous models under the energy constraint of large-scale AIoT systems but also improve the model performance of each involved heterogeneous device.

AdaNovo: Adaptive \emph{De Novo} Peptide Sequencing with Conditional Mutual Information

Tandem mass spectrometry has played a pivotal role in advancing proteomics, enabling the analysis of protein composition in biological samples. Despite the development of various deep learning methods for identifying amino acid sequences (peptides) responsible for observed spectra, challenges persist in \emph{de novo} peptide sequencing. Firstly, prior methods struggle to identify amino acids with post-translational modifications (PTMs) due to their lower frequency in training data compared to canonical amino acids, further resulting in decreased peptide-level identification precision. Secondly, diverse types of noise and missing peaks in mass spectra reduce the reliability of training data (peptide-spectrum matches, PSMs). To address these challenges, we propose AdaNovo, a novel framework that calculates conditional mutual information (CMI) between the spectrum and each amino acid/peptide, using CMI for adaptive model training. Extensive experiments demonstrate AdaNovo's state-of-the-art performance on a 9-species benchmark, where the peptides in the training set are almost completely disjoint from the peptides of the test sets. Moreover, AdaNovo excels in identifying amino acids with PTMs and exhibits robustness against data noise. The supplementary materials contain the official code.

A Graph is Worth $K$ Words: Euclideanizing Graph using Pure Transformer

Can we model non-Euclidean graphs as pure language or even Euclidean vectors while retaining their inherent information? The non-Euclidean property have posed a long term challenge in graph modeling. Despite recent GNN and Graphformer efforts encoding graphs as Euclidean vectors, recovering original graph from the vectors remains a challenge. We introduce GraphsGPT, featuring a Graph2Seq encoder that transforms non-Euclidean graphs into learnable graph words in a Euclidean space, along with a GraphGPT decoder that reconstructs the original graph from graph words to ensure information equivalence. We pretrain GraphsGPT on 100M molecules and yield some interesting findings: (1) Pretrained Graph2Seq excels in graph representation learning, achieving state-of-the-art results on 8/9 graph classification and regression tasks. (2) Pretrained GraphGPT serves as a strong graph generator, demonstrated by its ability to perform both unconditional and conditional graph generation. (3) Graph2Seq+GraphGPT enables effective graph mixup in the Euclidean space, overcoming previously known non-Euclidean challenge. (4) Our proposed novel edge-centric GPT pretraining task is effective in graph fields, underscoring its success in both representation and generation.

Online Differentiable Clustering for Intent Learning in Recommendation

Mining users' intents plays a crucial role in sequential recommendation. The recent approach, ICLRec, was introduced to extract underlying users' intents using contrastive learning and clustering. While it has shown effectiveness, the existing method suffers from complex and cumbersome alternating optimization, leading to two main issues. Firstly, the separation of representation learning and clustering optimization within a generalized expectation maximization (EM) framework often results in sub-optimal performance. Secondly, performing clustering on the entire dataset hampers scalability for large-scale industry data. To address these challenges, we propose a novel intent learning method called \underline{ODCRec}, which integrates representation learning into an \underline{O}nline \underline{D}ifferentiable \underline{C}lustering framework for \underline{Rec}ommendation. Specifically, we encode users' behavior sequences and initialize the cluster centers as differentiable network parameters. Additionally, we design a clustering loss that guides the networks to differentiate between different cluster centers and pull similar samples towards their respective cluster centers. This allows simultaneous optimization of recommendation and clustering using mini-batch data. Moreover, we leverage the learned cluster centers as self-supervision signals for representation learning, resulting in further enhancement of recommendation performance. Extensive experiments conducted on open benchmarks and industry data validate the superiority, effectiveness, and efficiency of our proposed ODCRec method. Code is available at: https://github.com/yueliu1999/ELCRec.

Deep Manifold Graph Auto-Encoder for Attributed Graph Embedding

Representing graph data in a low-dimensional space for subsequent tasks is the purpose of attributed graph embedding. Most existing neural network approaches learn latent representations by minimizing reconstruction errors. Rare work considers the data distribution and the topological structure of latent codes simultaneously, which often results in inferior embeddings in real-world graph data. This paper proposes a novel Deep Manifold (Variational) Graph Auto-Encoder (DMVGAE/DMGAE) method for attributed graph data to improve the stability and quality of learned representations to tackle the crowding problem. The node-to-node geodesic similarity is preserved between the original and latent space under a pre-defined distribution. The proposed method surpasses state-of-the-art baseline algorithms by a significant margin on different downstream tasks across popular datasets, which validates our solutions. We promise to release the code after acceptance.

Masked Modeling for Self-supervised Representation Learning on Vision and Beyond

As the deep learning revolution marches on, self-supervised learning has garnered increasing attention in recent years thanks to its remarkable representation learning ability and the low dependence on labeled data. Among these varied self-supervised techniques, masked modeling has emerged as a distinctive approach that involves predicting parts of the original data that are proportionally masked during training. This paradigm enables deep models to learn robust representations and has demonstrated exceptional performance in the context of computer vision, natural language processing, and other modalities. In this survey, we present a comprehensive review of the masked modeling framework and its methodology. We elaborate on the details of techniques within masked modeling, including diverse masking strategies, recovering targets, network architectures, and more. Then, we systematically investigate its wide-ranging applications across domains. Furthermore, we also explore the commonalities and differences between masked modeling methods in different fields. Toward the end of this paper, we conclude by discussing the limitations of current techniques and point out several potential avenues for advancing masked modeling research. A paper list project with this survey is available at \url{https://github.com/Lupin1998/Awesome-MIM}.

Graph-level Protein Representation Learning by Structure Knowledge Refinement

This paper focuses on learning representation on the whole graph level in an unsupervised manner. Learning graph-level representation plays an important role in a variety of real-world issues such as molecule property prediction, protein structure feature extraction, and social network analysis. The mainstream method is utilizing contrastive learning to facilitate graph feature extraction, known as Graph Contrastive Learning (GCL). GCL, although effective, suffers from some complications in contrastive learning, such as the effect of false negative pairs. Moreover, augmentation strategies in GCL are weakly adaptive to diverse graph datasets. Motivated by these problems, we propose a novel framework called Structure Knowledge Refinement (SKR) which uses data structure to determine the probability of whether a pair is positive or negative. Meanwhile, we propose an augmentation strategy that naturally preserves the semantic meaning of the original data and is compatible with our SKR framework. Furthermore, we illustrate the effectiveness of our SKR framework through intuition and experiments. The experimental results on the tasks of graph-level classification demonstrate that our SKR framework is superior to most state-of-the-art baselines.

MMDesign: Multi-Modality Transfer Learning for Generative Protein Design

Protein design involves generating protein sequences based on their corresponding protein backbones. While deep generative models show promise for learning protein design directly from data, the lack of publicly available structure-sequence pairings limits their generalization capabilities. Previous efforts of generative protein design have focused on architectural improvements and pseudo-data augmentation to overcome this bottleneck. To further address this challenge, we propose a novel protein design paradigm called MMDesign, which leverages multi-modality transfer learning. To our knowledge, MMDesign is the first framework that combines a pretrained structural module with a pretrained contextual module, using an auto-encoder (AE) based language model to incorporate prior semantic knowledge of protein sequences. We also introduce a cross-layer cross-modal alignment algorithm to enable the structural module to learn long-term temporal information and ensure consistency between structural and contextual modalities. Experimental results, only training with the small CATH dataset, demonstrate that our MMDesign framework consistently outperforms other baselines on various public test sets. To further assess the biological plausibility of the generated protein sequences and data distribution, we present systematic quantitative analysis techniques that provide interpretability and reveal more about the laws of protein design.