Guangyong Chen

Yaodong Yang, Yang Wang, Jinpeng Li et al.

Protein evolution through amino acid sequence mutations is a cornerstone of life sciences. While current in-silicon directed evolution algorithms largely focus on designing heuristic search strategies, they overlook how to integrate the transformative protein language models, which encode rich evolutionary patterns, with reinforcement learning to learn to directly evolve proteins. To bridge this gap, we propose AlphaDE, a novel framework to optimize protein sequences by harnessing the innovative paradigms of large language models such as fine-tuning and test-time inference. First, AlphaDE fine-tunes pretrained protein language models using masked language modeling on homologous protein sequences to activate the evolutionary plausibility for the interested protein class. Second, AlphaDE introduces test-time inference based on Monte Carlo tree search, which effectively evolves proteins with evolutionary guidance from the fine-tuned protein language model. Extensive benchmark experiments show that AlphaDE remarkably outperforms previous state-of-the-art methods even with few-shot fine-tuning. A further case study demonstrates that AlphaDE supports condensing the protein sequence space of avGFP through computational evolution.

Junde Xu, Yapin Shi, Lijun Lang et al.

Multimodal protein language models deliver strong performance on mutation-effect prediction, but training such models from scratch demands substantial computational resources. In this paper, we propose a fine-tuning framework called InstructPLM-mu and try to answer a question: \textit{Can multimodal fine-tuning of a pretrained, sequence-only protein language model match the performance of models trained end-to-end? } Surprisingly, our experiments show that fine-tuning ESM2 with structural inputs can reach performance comparable to ESM3. To understand how this is achieved, we systematically compare three different feature-fusion designs and fine-tuning recipes. Our results reveal that both the fusion method and the tuning strategy strongly affect final accuracy, indicating that the fine-tuning process is not trivial. We hope this work offers practical guidance for injecting structure into pretrained protein language models and motivates further research on better fusion mechanisms and fine-tuning protocols.

Sheng Lian, Dengfeng Pan, Jianlong Cai et al.

Accurate lumbar spine segmentation is crucial for diagnosing spinal disorders. Existing methods typically use coarse-grained segmentation strategies that lack the fine detail needed for precise diagnosis. Additionally, their reliance on visual-only models hinders the capture of anatomical semantics, leading to misclassified categories and poor segmentation details. To address these limitations, we present ATM-Net, an innovative framework that employs an anatomy-aware, text-guided, multi-modal fusion mechanism for fine-grained segmentation of lumbar substructures, i.e., vertebrae (VBs), intervertebral discs (IDs), and spinal canal (SC). ATM-Net adopts the Anatomy-aware Text Prompt Generator (ATPG) to adaptively convert image annotations into anatomy-aware prompts in different views. These insights are further integrated with image features via the Holistic Anatomy-aware Semantic Fusion (HASF) module, building a comprehensive anatomical context. The Channel-wise Contrastive Anatomy-Aware Enhancement (CCAE) module further enhances class discrimination and refines segmentation through class-wise channel-level multi-modal contrastive learning. Extensive experiments on the MRSpineSeg and SPIDER datasets demonstrate that ATM-Net significantly outperforms state-of-the-art methods, with consistent improvements regarding class discrimination and segmentation details. For example, ATM-Net achieves Dice of 79.39% and HD95 of 9.91 pixels on SPIDER, outperforming the competitive SpineParseNet by 8.31% and 4.14 pixels, respectively.

Guangyong Chen, Pengfei Chen, Chang-Yu Hsieh et al.

We introduce a new molecular dataset, named Alchemy, for developing machine learning models useful in chemistry and material science. As of June 20th 2019, the dataset comprises of 12 quantum mechanical properties of 119,487 organic molecules with up to 14 heavy atoms, sampled from the GDB MedChem database. The Alchemy dataset expands the volume and diversity of existing molecular datasets. Our extensive benchmarks of the state-of-the-art graph neural network models on Alchemy clearly manifest the usefulness of new data in validating and developing machine learning models for chemistry and material science. We further launch a contest to attract attentions from researchers in the related fields. More details can be found on the contest website \footnote{https://alchemy.tencent.com}. At the time of benchamrking experiment, we have generated 119,487 molecules in our Alchemy dataset. More molecular samples are generated since then. Hence, we provide a list of molecules used in the reported benchmarks.

Pengfei Chen, Weiwen Liu, Chang-Yu Hsieh et al.

Graph Neural Networks (GNNs) achieve an impressive performance on structured graphs by recursively updating the representation vector of each node based on its neighbors, during which parameterized transformation matrices should be learned for the node feature updating. However, existing propagation schemes are far from being optimal since they do not fully utilize the relational information between nodes. We propose the information maximizing graph neural networks (IGNN), which maximizes the mutual information between edge states and transform parameters. We reformulate the mutual information as a differentiable objective via a variational approach. We compare our model against several recent variants of GNNs and show that our model achieves the state-of-the-art performance on multiple tasks including quantum chemistry regression on QM9 dataset, generalization capability from QM9 to larger molecular graphs, and prediction of molecular bioactivities relevant for drug discovery. The IGNN model is based on an elegant and fundamental idea in information theory as explained in the main text, and it could be easily generalized beyond the contexts of molecular graphs considered in this work. To encourage more future work in this area, all datasets and codes used in this paper will be released for public access.