Peptide sequencing—the process of identifying amino acid sequences from mass spectrometry data—is a fundamental task in proteomics. Non-Autoregressive Transformers (NATs) have proven highly effective for this task, outperforming traditional methods. Unlike autoregressive models, which generate tokens sequentially, NATs predict all positions simultaneously, leveraging bidirectional context through unmasked self-attention. However, existing NAT approaches often rely on Connectionist Temporal Classification (CTC) loss, which presents significant optimization challenges due to CTC’s complexity and increases the risk of training failures. To address these issues, we propose an improved non-autoregressive peptide sequencing model that incorporates a structured protein sequence curriculum learning strategy. This approach adjusts protein’s learning difficulty based on the model’s estimated protein generational capabilities through a sampling process, progressively learning peptide generation from simple to complex sequences. Additionally, we introduce a self-refining inference-time module that iteratively enhances predictions using learned NAT token embeddings, improving sequence accuracy at a fine-grained level. Our curriculum learning strategy reduces NAT training failures frequency by more than 90% based on sampled training over various data distributions. Evaluations on nine benchmark species demonstrate that our approach outperforms all previous methods across multiple metrics and species. Model and source code are available at https://github.com/BEAM-Labs/denovo.

De novo peptide sequencing is a critical task in proteomics. However, the performance of current deep learning-based methods is limited by the inherent complexity of mass spectrometry data and the heterogeneous distribution of noise signals, leading to data-specific biases. We present RankNovo, the first deep reranking framework that enhances de novo peptide sequencing by leveraging the complementary strengths of multiple sequencing models. RankNovo employs a list-wise reranking approach, modeling candidate peptides as multiple sequence alignments and utilizing axial attention to extract informative features across candidates. Additionally, we introduce two new metrics, PMD (Peptide Mass Deviation) and RMD (ResidualMass Deviation), which offer delicate supervision by quantifying mass differences between peptides at both the sequence and residue levels. Extensive experiments demonstrate that RankNovo not only surpasses its base models used to generate training candidates for reranking pre-training, but also sets a new state-of-the-art benchmark. Moreover, RankNovo exhibits strong zero-shot generalization to unseen models—those whose generations were not exposed during training, highlighting its robustness and potential as a universal reranking framework for peptide sequencing. Our work presents a novel reranking strategy that fundamentally challenges existing single-model paradigms and advances the frontier of accurate de novo sequencing. Our source code is provided on GitHub.

Retrieval-augmented generation (RAG) has become a widely adopted paradigm for enabling knowledge-grounded large language models (LLMs). However, standard RAG pipelines often fail to ensure that model reasoning remains consistent with the evidence retrieved, leading to factual inconsistencies or unsupported conclusions. In this work, we reinterpret RAG as \textit{Retrieval-Augmented Reasoning} and identify a central but underexplored problem: \textit{Reasoning Misalignment}—the divergence between an LLM's internal reasoning trajectory and the evidential constraints provided by retrieval. To address this issue, we propose \textsc{AlignRAG}, a novel iterative framework grounded in \textit{Critique-Driven Alignment (CDA)}. We further introduce \textsc{AlignRAG-auto}, an autonomous variant that dynamically terminates refinement, removing the need to pre-specify the number of critique iterations. At the heart of \textsc{AlignRAG} lies a \textit{contrastive critique synthesis} mechanism that generates retrieval-sensitive critiques while mitigating self-bias. This mechanism trains a dedicated retrieval-augmented \textit{Critic Language Model (CLM)} using labeled critiques that distinguish between evidence-aligned and misaligned reasoning. Empirical evaluations show that our approach significantly improves reasoning fidelity. Our 8B-parameter CLM improves performance over the Self-Refine baseline by \textbf{12.1\%} on out-of-domain tasks and outperforms a standard 72B-parameter CLM by \textbf{2.2\%}. Furthermore, \textsc{AlignRAG-auto} achieves this state-of-the-art performance while dynamically determining the optimal number of refinement steps, enhancing efficiency and usability. \textsc{AlignRAG} remains compatible with existing RAG architectures as a \textit{plug-and-play} module and demonstrates strong robustness under both informative and noisy retrieval scenarios. Overall, \textsc{AlignRAG} offers a principled solution for aligning model reasoning with retrieved evidence, substantially improving the factual reliability and robustness of RAG systems. Our source code is provided at \href{https://github.com/upup-wei/RAG-ReasonAlignment}{link}.

Autoregressive (AR) models, common in sequence generation, are limited in many biological tasks like de novo peptide sequencing and protein modeling by their unidirectional nature, failing to capture crucial global bidirectional token dependencies. Non-Autoregressive (NAR) models offer holistic, bidirectional representations but face challenges with generative coherence and scalability. To transcend this, we propose a hybrid framework enhancing AR generation by dynamically integrating rich contextual information from non-autoregressive mechanisms. Our approach couples a shared input encoder with two decoders: a non-autoregressive one learning latent bidirectional biological features, and an AR decoder synthesizing the biological sequence by leveraging these bidirectional features. A novel cross-decoder attention module enables the AR decoder to iteratively query and integrate these bidirectional features, enriching its predictions. This synergy is cultivated via a tailored training strategy with importance annealing for balanced objectives and cross-decoder gradient blocking for stable, focused learning. Evaluations on a demanding 9-species benchmark of de novo peptide sequencing task show our model substantially surpasses AR and NAR baselines. It uniquely harmonizes AR stability with NAR contextual awareness, delivering robust, superior performance on diverse downstream data. This research advances biological sequence modeling techniques and contributes a novel architectural paradigm for augmenting AR models with enhanced bidirectional understanding for complex sequence generation. Our code is available on GitHub: https://github.com/BEAM-Labs/denovo

In the field of the Internet of Things, sensors with large-scale perception ability are urgently needed for the scenarios, such as structure health monitoring, vehicle tracking, and so on. Quasi-distributed acoustic sensing (QDAS), which uses a sensing fiber with an ultraweak reflector array to perceive thousands of points at the same time, shows great advantages in these applications. The sensing fiber integrates sensing and transmission functionalities together and is easy to be deployed on large-scale targets. With the development of QDAS, the performance limitations caused by the finite frequency-domain resource are gradually emerging. Multiplexing the frequency-domain resource can be the key to further performance breakthroughs. For this purpose, the multiple-input–multiple-output (MIMO) technology, which has been widely used in communication/radar systems, is introduced into QDAS in this article. The principles of QDAS with the MIMO technology are elaborated, and the feasibility is verified through simulations and experiments, in which the response bandwidth is tripled compared to the traditional single-pulse QDAS. To the best of our knowledge, this is the first time that the MIMO coding technology, i.e., orthogonal codes with the same frequency (OCSF), is used in QDAS. This work paves a new way for breaking QDAS performance limitations that are bounded by the finite frequency resource.