Xiaochen Bo

Zijun Min, Bingshuai Liu, Liang Zhang et al.

The field of bioinformatics has seen significant progress, making the cross-modal text-molecule retrieval task increasingly vital. This task focuses on accurately retrieving molecule structures based on textual descriptions, by effectively aligning textual descriptions and molecules to assist researchers in identifying suitable molecular candidates. However, many existing approaches overlook the details inherent in molecule sub-structures. In this work, we introduce the Optimal TRansport-based Multi-grained Alignments model (ORMA), a novel approach that facilitates multi-grained alignments between textual descriptions and molecules. Our model features a text encoder and a molecule encoder. The text encoder processes textual descriptions to generate both token-level and sentence-level representations, while molecules are modeled as hierarchical heterogeneous graphs, encompassing atom, motif, and molecule nodes to extract representations at these three levels. A key innovation in ORMA is the application of Optimal Transport (OT) to align tokens with motifs, creating multi-token representations that integrate multiple token alignments with their corresponding motifs. Additionally, we employ contrastive learning to refine cross-modal alignments at three distinct scales: token-atom, multitoken-motif, and sentence-molecule, ensuring that the similarities between correctly matched text-molecule pairs are maximized while those of unmatched pairs are minimized. To our knowledge, this is the first attempt to explore alignments at both the motif and multi-token levels. Experimental results on the ChEBI-20 and PCdes datasets demonstrate that ORMA significantly outperforms existing state-of-the-art (SOTA) models.

Yujie Qin, Ming He, Changyong Yu et al.

The de novo design of proteins refers to creating proteins with specific structures and functions that do not naturally exist. In recent years, the accumulation of high-quality protein structure and sequence data and technological advancements have paved the way for the successful application of generative artificial intelligence (AI) models in protein design. These models have surpassed traditional approaches that rely on fragments and bioinformatics. They have significantly enhanced the success rate of de novo protein design, and reduced experimental costs, leading to breakthroughs in the field. Among various generative AI models, diffusion models have yielded the most promising results in protein design. In the past two to three years, more than ten protein design models based on diffusion models have emerged. Among them, the representative model, RFDiffusion, has demonstrated success rates in 25 protein design tasks that far exceed those of traditional methods, and other AI-based approaches like RFjoint and hallucination. This review will systematically examine the application of diffusion models in generating protein backbones and sequences. We will explore the strengths and limitations of different models, summarize successful cases of protein design using diffusion models, and discuss future development directions.

XU Wang, Huan Zhao, Weiwei TU et al.

Double-strand DNA breaks (DSBs) are a form of DNA damage that can cause abnormal chromosomal rearrangements. Recent technologies based on high-throughput experiments have obvious high costs and technical challenges.Therefore, we design a graph neural network based method to predict DSBs (GraphDSB), using DNA sequence features and chromosome structure information. In order to improve the expression ability of the model, we introduce Jumping Knowledge architecture and several effective structural encoding methods. The contribution of structural information to the prediction of DSBs is verified by the experiments on datasets from normal human epidermal keratinocytes (NHEK) and chronic myeloid leukemia cell line (K562), and the ablation studies further demonstrate the effectiveness of the designed components in the proposed GraphDSB framework. Finally, we use GNNExplainer to analyze the contribution of node features and topology to DSBs prediction, and proved the high contribution of 5-mer DNA sequence features and two chromatin interaction modes.

Lingwei Xie, Song He, Shu Yang et al.

With the rapid development of high-throughput technologies, parallel acquisition of large-scale drug-informatics data provides huge opportunities to improve pharmaceutical research and development. One significant application is the purpose prediction of small molecule compounds, aiming to specify therapeutic properties of extensive purpose-unknown compounds and to repurpose novel therapeutic properties of FDA-approved drugs. Such problem is very challenging since compound attributes contain heterogeneous data with various feature patterns such as drug fingerprint, drug physicochemical property, drug perturbation gene expression. Moreover, there is complex nonlinear dependency among heterogeneous data. In this paper, we propose a novel domain-adversarial multi-task framework for integrating shared knowledge from multiple domains. The framework utilizes the adversarial strategy to effectively learn target representations and models their nonlinear dependency. Experiments on two real-world datasets illustrate that the performance of our approach obtains an obvious improvement over competitive baselines. The novel therapeutic properties of purpose-unknown compounds we predicted are mostly reported or brought to the clinics. Furthermore, our framework can integrate various attributes beyond the three domains examined here and can be applied in the industry for screening the purpose of huge amounts of as yet unidentified compounds. Source codes of this paper are available on Github.