O-linked β-N-acetylglucosamine (O-GlcNAc) is a distinct monosaccharide modification of serine (S) or threonine (T) residues of nucleocytoplasmic and mitochondrial proteins. O-GlcNAc modification (i.e., O-GlcNAcylation) is involved in the regulation of diverse cellular processes, including transcription, epigenetic modifications, and cell signaling. Despite the great progress in experimentally mapping O-GlcNAc sites, there is an unmet need to develop robust prediction tools that can effectively locate the presence of O-GlcNAc sites in protein sequences of interest. In this work, we performed a comprehensive evaluation of a framework for prediction of protein O-GlcNAc sites using embeddings from pre-trained protein language models. In particular, we compared the performance of three protein sequence-based large protein language models (pLMs), Ankh, ESM-2, and ProtT5, for prediction of O-GlcNAc sites and also evaluated various ensemble strategies to integrate embeddings from these protein language models. Upon investigation, the decision-level fusion approach that integrates the decisions of the three embedding models, which we call LM-OGlcNAc-Site, outperformed the models trained on these individual language models as well as other fusion approaches and other existing predictors in almost all of the parameters evaluated. The precise prediction of O-GlcNAc sites will facilitate the probing of O-GlcNAc site-specific functions of proteins in physiology and diseases. Moreover, these findings also indicate the effectiveness of combined uses of multiple protein language models in post-translational modification prediction and open exciting avenues for further research and exploration in other protein downstream tasks. LM-OGlcNAc-Site’s web server and source code are publicly available to the community.

Older adults are more vulnerable to falling due to normal changes due to aging, and their falls are a serious medical risk with high healthcare and societal costs. However, there is a lack of automatic fall detection systems for older adults. This paper reports (1) a wireless, flexible, skin-wearable electronic device for both accurate motion sensing and user comfort, and (2) a deep learning-based classification algorithm for reliable fall detection of older adults. The cost-effective skin-wearable motion monitoring device is designed and fabricated using thin copper films. It includes a six-axis motion sensor and is directly laminated on the skin without adhesives for the collection of accurate motion data. To study accurate fall detection using the proposed device, different deep learning models, body locations for the device placement, and input datasets are investigated using motion data based on various human activities. Our results indicate the optimal location to place the device is the chest, achieving accuracy of more than 98% for falls with motion data from older adults. Moreover, our results suggest a large motion dataset directly collected from older adults is essential to improve the accuracy of fall detection for the older adult population.

Motivation: The mapping from codon to amino acid is surjective due to codon degeneracy, suggesting that codon space might harbor higher information content. Embeddings from the codon language model have recently demonstrated success in various protein downstream tasks. However, predictive models for residue-level tasks such as phosphorylation sites, arguably the most studied Post-Translational Modification (PTM), and PTM sites prediction in general, have predominantly relied on representations in amino acid space. Results: We introduce a novel approach for predicting phosphorylation sites by utilizing codon-level information through embeddings from the codon adaptation language model (CaLM), trained on protein-coding DNA sequences. Protein sequences are first reverse-translated into reliable coding sequences by mapping UniProt sequences to their corresponding NCBI reference sequences and extracting the exact coding sequences from their GenBank format using a dynamic programming-based global pairwise alignment. The resulting coding sequences are encoded using the CaLM encoder to generate codon-aware embeddings, which are subsequently integrated with amino acid-aware embeddings obtained from a protein language model, through an early fusion strategy. Next, a window-level representation of the site of interest, retaining the full sequence context, is constructed from the fused embeddings. A ConvBiGRU network extracts feature maps that capture spatiotemporal correlations between proximal residues within the window. This is followed by a prediction head based on a Kolmogorov-Arnold network (KAN) using the derivative of gaussian wavelet transform to generate the inference for the site. The overall model, dubbed CaLMPhosKAN, performs better than the existing approaches across multiple datasets. Availability and implementation: CaLMPhosKAN is publicly available at https://github.com/KCLabMTU/CaLMPhosKAN.

DNA-binding proteins (DBPs) play a crucial role in gene regulation, development, and environmental responses across plants, animals, and microorganisms. Existing DBP prediction methods are largely limited to sequence information, whether through handcrafted features or sequence-based protein language models (PLMs), overlooking structural cues critical to protein function. In addition, most existing tools are trained for general DBP predictions, which are often not accurate for plant-specific DBPs due to the unique structural and functional properties of plant proteins. Our work introduces PLM-DBPs, a deep learning framework that integrates both sequence-based and structure-aware representations to enhance DBP prediction in plants. We evaluated several state-of-the-art PLMs to extract high-dimensional protein representations and experimented with various fusion strategies to validate the complementary information between the various representations. Our final model, a fusion of sequence-based and structure-aware ANN models, achieves a notable improvement in predicting DBPs in plants outperforming previous state-of-the-art models. Although sequence-based PLMs already demonstrate strong performance in DBP prediction, our findings show that the integration of structural information further enhances predictive accuracy. This underscores the complementary nature of structural representations and establishes PLM-DBPs as a robust tool for advancing plant research and agricultural innovation. The proposed model and other resources are publicly available at https://github.com/suresh-pokharel/PLM-DBPs

DNA-binding proteins (DBPs) play critical roles in gene regulation, development, and environmental response across various species, including plants, animals, and microorganisms. While various machine learning and deep learning models have been developed to distinguish DNA-binding proteins (DBPs) from non-DNA-binding proteins (NDBPs), most available tools have focused on human and mouse datasets. As a result, there are limited studies specifically addressing plant-based DNA-binding proteins, which restricts our understanding of their unique roles and functions in plant biology. Developing an efficient framework for improving DBP prediction in plants would enhance our knowledge and enable precise gene expression control, accelerate crop improvement, enhance stress resilience, and optimize metabolic engineering for agricultural advancement. In this work, we developed a tool that uses a protein language model (pLM) pre-trained on millions of sequences. We evaluated several leading models, including ProtT5, Ankh, and ESM-2, and leveraged their high-dimensional, information-rich representations to improve the accuracy of DNA-binding protein prediction in plants significantly. Our final model, pLM-DBPs, a feed-forward neural network classifier utilizing ProtT5-based representations, outperformed existing approaches with a Matthews Correlation Coefficient (MCC) of 83.8% on the independent test set. This represents a 10% improvement over the previous state-of-the-art model for plant-based DBP prediction, highlighting its superior performance compared to the existing approaches.

A bstract: Post-translational modifications (PTMs) are chemical changes added to proteins after translation. These changes affect protein function and regulation, and their disruption is linked to disease-associated mechanisms. Because experimentally validating all possible modification sites is impractical, many computational predictors have been developed for PTM site prediction. In this work, we study whether a shared model can represent common residue-background patterns while learning modification-specific background-to-positive offsets. This framing is especially relevant for residues such as lysine (K), which can be acetylated, ubiquitinated, methylated, or sumoylated depending on the surrounding protein context. We propose an anchor-guided rectified flow matching framework for multi-type PTM site prediction from protein language model embeddings. For each PTM–residue pair, the model builds residue-background anchors from PTM-compatible unannotated residues and positive anchors from experimentally annotated modified residues. Given a candidate residue and target modification type, the model compares the residue embedding with these anchor sets and uses a rectified flow module to estimate a modification-conditioned background-to-positive offset. This offset is combined with anchor-based features and used for site scoring. We evaluate the framework on a dbPTM-derived benchmark covering six commonly studied PTMs: phosphorylation, acetylation, ubiquitination, methylation, sumoylation, and N-linked glycosylation. In the shared-model setting, our approach achieves a macro AUPRC of 0.4195, improving over the gated multi-anchor baseline of 0.4154, while independently trained per-modification models achieve 0.4353. These results suggest that multi-type PTM prediction can be modeled within a single shared framework by combining residue-background anchors with modification-conditioned offset features.