Acquiring Pronunciation Knowledge from Transcribed Speech Audio via Multi-task Learning

Recent work has shown the feasibility and benefit of bootstrapping an integrated sequence-to-sequence (Seq2Seq) linguistic frontend from a traditional pipeline-based frontend for text-to-speech (TTS). To overcome the fixed lexical coverage of bootstrapping training data, previous work has proposed to leverage easily accessible transcribed speech audio as an additional training source for acquiring novel pronunciation knowledge for uncovered words, which relies on an auxiliary ASR model as part of a cumbersome implementation flow. In this work, we propose an alternative method to leverage transcribed speech audio as an additional training source, based on multi-task learning (MTL). Experiments show that, compared to a baseline Seq2Seq frontend, the proposed MTL-based method reduces PER from 2.5% to 1.6% for those word types covered exclusively in transcribed speech audio, achieving a similar performance to the previous method but with a much simpler implementation flow.

AccentBox: Towards High-Fidelity Zero-Shot Accent Generation

While recent Zero-Shot Text-to-Speech (ZS-TTS) models have achieved high naturalness and speaker similarity, they fall short in accent fidelity and control. To address this issue, we propose zero-shot accent generation that unifies Foreign Accent Conversion (FAC), accented TTS, and ZS-TTS, with a novel two-stage pipeline. In the first stage, we achieve state-of-the-art (SOTA) on Accent Identification (AID) with 0.56 f1 score on unseen speakers. In the second stage, we condition ZS-TTS system on the pretrained speaker-agnostic accent embeddings extracted by the AID model. The proposed system achieves higher accent fidelity on inherent/cross accent generation, and enables unseen accent generation.

BEACON: Benchmark for Comprehensive RNA Tasks and Language Models

RNA plays a pivotal role in translating genetic instructions into functional outcomes, underscoring its importance in biological processes and disease mechanisms. Despite the emergence of numerous deep learning approaches for RNA, particularly universal RNA language models, there remains a significant lack of standardized benchmarks to assess the effectiveness of these methods. In this study, we introduce the first comprehensive RNA benchmark BEACON (\textbf{BE}nchm\textbf{A}rk for \textbf{CO}mprehensive R\textbf{N}A Task and Language Models). First, BEACON comprises 13 distinct tasks derived from extensive previous work covering structural analysis, functional studies, and engineering applications, enabling a comprehensive assessment of the performance of methods on various RNA understanding tasks. Second, we examine a range of models, including traditional approaches like CNNs, as well as advanced RNA foundation models based on language models, offering valuable insights into the task-specific performances of these models. Third, we investigate the vital RNA language model components from the tokenizer and positional encoding aspects. Notably, our findings emphasize the superiority of single nucleotide tokenization and the effectiveness of Attention with Linear Biases (ALiBi) over traditional positional encoding methods. Based on these insights, a simple yet strong baseline called BEACON-B is proposed, which can achieve outstanding performance with limited data and computational resources. The datasets and source code of our benchmark are available at https://github.com/terry-r123/RNABenchmark.

Safeguarding Large Language Models: A Survey

In the burgeoning field of Large Language Models (LLMs), developing a robust safety mechanism, colloquially known as "safeguards" or "guardrails", has become imperative to ensure the ethical use of LLMs within prescribed boundaries. This article provides a systematic literature review on the current status of this critical mechanism. It discusses its major challenges and how it can be enhanced into a comprehensive mechanism dealing with ethical issues in various contexts. First, the paper elucidates the current landscape of safeguarding mechanisms that major LLM service providers and the open-source community employ. This is followed by the techniques to evaluate, analyze, and enhance some (un)desirable properties that a guardrail might want to enforce, such as hallucinations, fairness, privacy, and so on. Based on them, we review techniques to circumvent these controls (i.e., attacks), to defend the attacks, and to reinforce the guardrails. While the techniques mentioned above represent the current status and the active research trends, we also discuss several challenges that cannot be easily dealt with by the methods and present our vision on how to implement a comprehensive guardrail through the full consideration of multi-disciplinary approach, neural-symbolic method, and systems development lifecycle.

Instruction Multi-Constraint Molecular Generation Using a Teacher-Student Large Language Model

While various models and computational tools have been proposed for structure and property analysis of molecules, generating molecules that conform to all desired structures and properties remains a challenge. Here, we introduce a multi-constraint molecular generation large language model, TSMMG, which, akin to a student, incorporates knowledge from various small models and tools, namely, the 'teachers'. To train TSMMG, we construct a large set of text-molecule pairs by extracting molecular knowledge from these 'teachers', enabling it to generate novel molecules that conform to the descriptions through various text prompts. We experimentally show that TSMMG remarkably performs in generating molecules meeting complex, natural language-described property requirements across two-, three-, and four-constraint tasks, with an average molecular validity of over 99% and success ratio of 88.08%, 65.27%, and 61.44%, respectively. The model also exhibits adaptability through zero-shot testing, creating molecules that satisfy combinations of properties that have not been encountered. It can comprehend text inputs with various language styles, extending beyond the confines of outlined prompts, as confirmed through empirical validation. Additionally, the knowledge distillation feature of TSMMG contributes to the continuous enhancement of small models, while the innovative approach to dataset construction effectively addresses the issues of data scarcity and quality, which positions TSMMG as a promising tool in the domains of drug discovery and materials science. Code is available at https://github.com/HHW-zhou/TSMMG.

ContraNovo: A Contrastive Learning Approach to Enhance De Novo Peptide Sequencing

De novo peptide sequencing from mass spectrometry (MS) data is a critical task in proteomics research. Traditional de novo algorithms have encountered a bottleneck in accuracy due to the inherent complexity of proteomics data. While deep learning-based methods have shown progress, they reduce the problem to a translation task, potentially overlooking critical nuances between spectra and peptides. In our research, we present ContraNovo, a pioneering algorithm that leverages contrastive learning to extract the relationship between spectra and peptides and incorporates the mass information into peptide decoding, aiming to address these intricacies more efficiently. Through rigorous evaluations on two benchmark datasets, ContraNovo consistently outshines contemporary state-of-the-art solutions, underscoring its promising potential in enhancing de novo peptide sequencing. The source code is available at https://github.com/BEAM-Labs/ContraNovo.

Enhancing the Protein Tertiary Structure Prediction by Multiple Sequence Alignment Generation

The field of protein folding research has been greatly advanced by deep learning methods, with AlphaFold2 (AF2) demonstrating exceptional performance and atomic-level precision. As co-evolution is integral to protein structure prediction, AF2's accuracy is significantly influenced by the depth of multiple sequence alignment (MSA), which requires extensive exploration of a large protein database for similar sequences. However, not all protein sequences possess abundant homologous families, and consequently, AF2's performance can degrade on such queries, at times failing to produce meaningful results. To address this, we introduce a novel generative language model, MSA-Augmenter, which leverages protein-specific attention mechanisms and large-scale MSAs to generate useful, novel protein sequences not currently found in databases. These sequences supplement shallow MSAs, enhancing the accuracy of structural property predictions. Our experiments on CASP14 demonstrate that MSA-Augmenter can generate de novo sequences that retain co-evolutionary information from inferior MSAs, thereby improving protein structure prediction quality on top of strong AF2.

Design, Actuation, and Functionalization of Untethered Soft Magnetic Robots with Life-Like Motions: A Review

Soft robots have demonstrated superior flexibility and functionality than conventional rigid robots. These versatile devices can respond to a wide range of external stimuli (including light, magnetic field, heat, electric field, etc.), and can perform sophisticated tasks. Notably, soft magnetic robots exhibit unparalleled advantages among numerous soft robots (such as untethered control, rapid response, and high safety), and have made remarkable progress in small-scale manipulation tasks and biomedical applications. Despite the promising potential, soft magnetic robots are still in their infancy and require significant advancements in terms of fabrication, design principles, and functional development to be viable for real-world applications. Recent progress shows that bionics can serve as an effective tool for developing soft robots. In light of this, the review is presented with two main goals: (i) exploring how innovative bioinspired strategies can revolutionize the design and actuation of soft magnetic robots to realize various life-like motions; (ii) examining how these bionic systems could benefit practical applications in small-scale solid/liquid manipulation and therapeutic/diagnostic-related biomedical fields.

AF2-Mutation: Adversarial Sequence Mutations against AlphaFold2 on Protein Tertiary Structure Prediction

Deep learning-based approaches, such as AlphaFold2 (AF2), have significantly advanced protein tertiary structure prediction, achieving results comparable to real biological experimental methods. While AF2 has shown limitations in predicting the effects of mutations, its robustness against sequence mutations remains to be determined. Starting with the wild-type (WT) sequence, we investigate adversarial sequences generated via an evolutionary approach, which AF2 predicts to be substantially different from WT. Our experiments on CASP14 reveal that by modifying merely three residues in the protein sequence using a combination of replacement, deletion, and insertion strategies, the alteration in AF2's predictions, as measured by the Local Distance Difference Test (lDDT), reaches 46.61. Moreover, when applied to a specific protein, SPNS2, our proposed algorithm successfully identifies biologically meaningful residues critical to protein structure determination and potentially indicates alternative conformations, thus significantly expediting the experimental process.

E2Efold-3D: End-to-End Deep Learning Method for accurate de novo RNA 3D Structure Prediction

RNA structure determination and prediction can promote RNA-targeted drug development and engineerable synthetic elements design. But due to the intrinsic structural flexibility of RNAs, all the three mainstream structure determination methods (X-ray crystallography, NMR, and Cryo-EM) encounter challenges when resolving the RNA structures, which leads to the scarcity of the resolved RNA structures. Computational prediction approaches emerge as complementary to the experimental techniques. However, none of the \textit{de novo} approaches is based on deep learning since too few structures are available. Instead, most of them apply the time-consuming sampling-based strategies, and their performance seems to hit the plateau. In this work, we develop the first end-to-end deep learning approach, E2Efold-3D, to accurately perform the \textit{de novo} RNA structure prediction. Several novel components are proposed to overcome the data scarcity, such as a fully-differentiable end-to-end pipeline, secondary structure-assisted self-distillation, and parameter-efficient backbone formulation. Such designs are validated on the independent, non-overlapping RNA puzzle testing dataset and reach an average sub-4 \AA{} root-mean-square deviation, demonstrating its superior performance compared to state-of-the-art approaches. Interestingly, it also achieves promising results when predicting RNA complex structures, a feat that none of the previous systems could accomplish. When E2Efold-3D is coupled with the experimental techniques, the RNA structure prediction field can be greatly advanced.