Scientific Large Language Models: A Survey on Biological & Chemical Domains

Large Language Models (LLMs) have emerged as a transformative power in enhancing natural language comprehension, representing a significant stride toward artificial general intelligence. The application of LLMs extends beyond conventional linguistic boundaries, encompassing specialized linguistic systems developed within various scientific disciplines. This growing interest has led to the advent of scientific LLMs, a novel subclass specifically engineered for facilitating scientific discovery. As a burgeoning area in the community of AI for Science, scientific LLMs warrant comprehensive exploration. However, a systematic and up-to-date survey introducing them is currently lacking. In this paper, we endeavor to methodically delineate the concept of "scientific language", whilst providing a thorough review of the latest advancements in scientific LLMs. Given the expansive realm of scientific disciplines, our analysis adopts a focused lens, concentrating on the biological and chemical domains. This includes an in-depth examination of LLMs for textual knowledge, small molecules, macromolecular proteins, genomic sequences, and their combinations, analyzing them in terms of model architectures, capabilities, datasets, and evaluation. Finally, we critically examine the prevailing challenges and point out promising research directions along with the advances of LLMs. By offering a comprehensive overview of technical developments in this field, this survey aspires to be an invaluable resource for researchers navigating the intricate landscape of scientific LLMs.

InstructProtein: Aligning Human and Protein Language via Knowledge Instruction

Large Language Models (LLMs) have revolutionized the field of natural language processing, but they fall short in comprehending biological sequences such as proteins. To address this challenge, we propose InstructProtein, an innovative LLM that possesses bidirectional generation capabilities in both human and protein languages: (i) taking a protein sequence as input to predict its textual function description and (ii) using natural language to prompt protein sequence generation. To achieve this, we first pre-train an LLM on both protein and natural language corpora, enabling it to comprehend individual languages. Then supervised instruction tuning is employed to facilitate the alignment of these two distinct languages. Herein, we introduce a knowledge graph-based instruction generation framework to construct a high-quality instruction dataset, addressing annotation imbalance and instruction deficits in existing protein-text corpus. In particular, the instructions inherit the structural relations between proteins and function annotations in knowledge graphs, which empowers our model to engage in the causal modeling of protein functions, akin to the chain-of-thought processes in natural languages. Extensive experiments on bidirectional protein-text generation tasks show that InstructProtein outperforms state-of-the-art LLMs by large margins. Moreover, InstructProtein serves as a pioneering step towards text-based protein function prediction and sequence design, effectively bridging the gap between protein and human language understanding.

Exploring Model Transferability through the Lens of Potential Energy

Transfer learning has become crucial in computer vision tasks due to the vast availability of pre-trained deep learning models. However, selecting the optimal pre-trained model from a diverse pool for a specific downstream task remains a challenge. Existing methods for measuring the transferability of pre-trained models rely on statistical correlations between encoded static features and task labels, but they overlook the impact of underlying representation dynamics during fine-tuning, leading to unreliable results, especially for self-supervised models. In this paper, we present an insightful physics-inspired approach named PED to address these challenges. We reframe the challenge of model selection through the lens of potential energy and directly model the interaction forces that influence fine-tuning dynamics. By capturing the motion of dynamic representations to decline the potential energy within a force-driven physical model, we can acquire an enhanced and more stable observation for estimating transferability. The experimental results on 10 downstream tasks and 12 self-supervised models demonstrate that our approach can seamlessly integrate into existing ranking techniques and enhance their performances, revealing its effectiveness for the model selection task and its potential for understanding the mechanism in transfer learning. Code will be available at https://github.com/lixiaotong97/PED.

Modeling Uncertain Feature Representation for Domain Generalization

Though deep neural networks have achieved impressive success on various vision tasks, obvious performance degradation still exists when models are tested in out-of-distribution scenarios. In addressing this limitation, we ponder that the feature statistics (mean and standard deviation), which carry the domain characteristics of the training data, can be properly manipulated to improve the generalization ability of deep learning models. Existing methods commonly consider feature statistics as deterministic values measured from the learned features and do not explicitly model the uncertain statistics discrepancy caused by potential domain shifts during testing. In this paper, we improve the network generalization ability by modeling domain shifts with uncertainty (DSU), i.e., characterizing the feature statistics as uncertain distributions during training. Specifically, we hypothesize that the feature statistic, after considering the potential uncertainties, follows a multivariate Gaussian distribution. During inference, we propose an instance-wise adaptation strategy that can adaptively deal with the unforeseeable shift and further enhance the generalization ability of the trained model with negligible additional cost. We also conduct theoretical analysis on the aspects of generalization error bound and the implicit regularization effect, showing the efficacy of our method. Extensive experiments demonstrate that our method consistently improves the network generalization ability on multiple vision tasks, including image classification, semantic segmentation, instance retrieval, and pose estimation. Our methods are simple yet effective and can be readily integrated into networks without additional trainable parameters or loss constraints. Code will be released in https://github.com/lixiaotong97/DSU.

Masked Image Modeling with Denoising Contrast

Since the development of self-supervised visual representation learning from contrastive learning to masked image modeling, there is no significant difference in essence, that is, how to design proper pretext tasks for vision dictionary look-up. Masked image modeling recently dominates this line of research with state-of-the-art performance on vision Transformers, where the core is to enhance the patch-level visual context capturing of the network via denoising auto-encoding mechanism. Rather than tailoring image tokenizers with extra training stages as in previous works, we unleash the great potential of contrastive learning on denoising auto-encoding and introduce a new pre-training method, ConMIM, to produce simple intra-image inter-patch contrastive constraints as the learning objectives for masked patch prediction. We further strengthen the denoising mechanism with asymmetric designs, including image perturbations and model progress rates, to improve the network pre-training. ConMIM-pretrained vision Transformers with various scales achieve promising results on downstream image classification, semantic segmentation, object detection, and instance segmentation tasks.

mc-BEiT: Multi-choice Discretization for Image BERT Pre-training

Image BERT pre-training with masked image modeling (MIM) becomes a popular practice to cope with self-supervised representation learning. A seminal work, BEiT, casts MIM as a classification task with a visual vocabulary, tokenizing the continuous visual signals into discrete vision tokens using a pre-learned dVAE. Despite a feasible solution, the improper discretization hinders further improvements of image pre-training. Since image discretization has no ground-truth answers, we believe that the masked patch should not be assigned with a unique token id even if a better tokenizer can be obtained. In this work, we introduce an improved BERT-style image pre-training method, namely mc-BEiT, which performs MIM proxy tasks towards eased and refined multi-choice training objectives. Specifically, the multi-choice supervision for the masked image patches is formed by the soft probability vectors of the discrete token ids, which are predicted by the off-the-shelf image tokenizer and further refined by high-level inter-patch perceptions resorting to the observation that similar patches should share their choices. Extensive experiments on classification, segmentation, and detection tasks demonstrate the superiority of our method, e.g., the pre-trained ViT-B achieves 84.1% top-1 fine-tuning accuracy on ImageNet-1K classification, 50.8% mIOU on ADE20K semantic segmentation, 51.2% AP^b and 44.3% AP^m of object detection and instance segmentation on COCO, outperforming the competitive counterparts.

Uncertainty Modeling for Out-of-Distribution Generalization

Though remarkable progress has been achieved in various vision tasks, deep neural networks still suffer obvious performance degradation when tested in out-of-distribution scenarios. We argue that the feature statistics (mean and standard deviation), which carry the domain characteristics of the training data, can be properly manipulated to improve the generalization ability of deep learning models. Common methods often consider the feature statistics as deterministic values measured from the learned features and do not explicitly consider the uncertain statistics discrepancy caused by potential domain shifts during testing. In this paper, we improve the network generalization ability by modeling the uncertainty of domain shifts with synthesized feature statistics during training. Specifically, we hypothesize that the feature statistic, after considering the potential uncertainties, follows a multivariate Gaussian distribution. Hence, each feature statistic is no longer a deterministic value, but a probabilistic point with diverse distribution possibilities. With the uncertain feature statistics, the models can be trained to alleviate the domain perturbations and achieve better robustness against potential domain shifts. Our method can be readily integrated into networks without additional parameters. Extensive experiments demonstrate that our proposed method consistently improves the network generalization ability on multiple vision tasks, including image classification, semantic segmentation, and instance retrieval. The code will be released soon at https://github.com/lixiaotong97/DSU.

Generalizable Person Re-identification with Relevance-aware Mixture of Experts

Domain generalizable (DG) person re-identification (ReID) is a challenging problem because we cannot access any unseen target domain data during training. Almost all the existing DG ReID methods follow the same pipeline where they use a hybrid dataset from multiple source domains for training, and then directly apply the trained model to the unseen target domains for testing. These methods often neglect individual source domains' discriminative characteristics and their relevances w.r.t. the unseen target domains, though both of which can be leveraged to help the model's generalization. To handle the above two issues, we propose a novel method called the relevance-aware mixture of experts (RaMoE), using an effective voting-based mixture mechanism to dynamically leverage source domains' diverse characteristics to improve the model's generalization. Specifically, we propose a decorrelation loss to make the source domain networks (experts) keep the diversity and discriminability of individual domains' characteristics. Besides, we design a voting network to adaptively integrate all the experts' features into the more generalizable aggregated features with domain relevance. Considering the target domains' invisibility during training, we propose a novel learning-to-learn algorithm combined with our relation alignment loss to update the voting network. Extensive experiments demonstrate that our proposed RaMoE outperforms the state-of-the-art methods.