arXiv subjects

Yanni Sun

Publications and source records attributed to Yanni Sun.

18 recordsLinked to original sources

arXiv2026

TPMM: Three-component Posterior Mixture Model Enables Robust Inverton Detection in Low-Depth Metagenomes and Suggests Potential Viral Invertons

Bacterial phase variation enables reversible, locus-specific phenotypic switching, often driven by DNA inversion (invertons). To identify these events, researchers commonly rely on sequencing reads that provide orientation-specific support. Metagenomic sequencing, which captures total genetic material independent of cultivation, offers a powerful platform for the comprehensive study of invertons. However, computational inverton calling from metagenomic data is difficult at low sequencing depth: hard read-support cutoffs can miss true events, while sequence-only predictors lack read-backed interpretability and uncertainty quantification. To address this, we present TPMM, a three-component posterior mixture model for inverton calling in metagenomic data. TPMM explicitly incorporates sequencing depth to formulate inverton detection as a probabilistic mixture problem. Starting from candidates flanked by inverted repeats, the model classifies the candidates into noise, low-probability, or high-probability inversion signals using read evidence. Finally, TPMM assigns posterior probabilities as soft labels and applies cumulative Bayesian False Discovery Rate control to robustly identify true invertons. On two real gut metagenomic datasets, TPMM agrees well with PhaseFinder at high depth but recovers substantially more invertons under systematic downsampling, demonstrating superior performance in sparse-data regimes. We further examine potential reversible inversion elements in viral genomes and provide supporting analyses, suggesting a broader scope for inversion-mediated regulation.

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arXiv2026

SeekRBP: Leveraging Sequence-Structure Integration with Reinforcement Learning for Receptor-Binding Protein Identification

Motivation: Receptor-binding proteins (RBPs) initiate viral infection and determine host specificity, serving as key targets for phage engineering and therapy. However, the identification of RBPs is complicated by their extreme sequence divergence, which often renders traditional homology-based alignment methods ineffective. While machine learning offers a promising alternative, such approaches struggle with severe class imbalance and the difficulty of selecting informative negative samples from heterogeneous tail proteins. Existing methods often fail to balance learning from these ``hard negatives'' while maintaining generalization. Results: We present SeekRBP, a sequence--structure framework that models negative sampling as a sequential decision-making problem. By employing a multi-armed bandit strategy, SeekRBP dynamically prioritizes informative non-RBP sequences based on real-time training feedback, complemented by a multimodal fusion of protein language and structural embeddings. Benchmarking demonstrates that SeekRBP consistently outperforms static sampling strategies. Furthermore, a case study on Vibrio phages validates that SeekRBP effectively identifies RBPs to improve host prediction, highlighting its potential for large-scale annotation and synthetic biology applications.

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arXiv2026

PhageMind: Generalized Strain-level Phage Host Range Prediction via Meta-learning

Bacteriophages (phages) are key regulators of bacterial populations and hold great promise for applications such as phage therapy, biocontrol, and industrial fermentation. The success of these applications depends on accurately determining phage host range, which is often specific at the strain level rather than the species level. However, existing computational approaches face major limitations: many rely on genus-specific features that do not generalize across taxa, while others require large amounts of training data that are unavailable for most bacterial lineages. These challenges create a critical need for methods that can accurately predict strain-level phage-host interactions across diverse bacterial genera, particularly under data-limited conditions. We present PhageMind, a learning framework designed to address this challenge by enabling efficient transfer of knowledge across bacterial genera. PhageMind is trained to identify shared principles of phage-bacterium interactions from well-studied systems and to rapidly adapt these principles to new genera using only a small number of known interactions. To reflect the biological basis of infection, we represent phage-host relationships using a knowledge graph that explicitly incorporates phage tail fiber proteins and bacterial O-antigen biosynthesis gene clusters, and we use this representation to guide interaction prediction. Across four bacterial genera (Escherichia, Klebsiella, Vibrio, and Alteromonas), PhageMind achieves high prediction accuracy and shows strong adaptability to new lineages. In particular, in leave-one-genus-out evaluations, the model maintains robust performance when only limited reference data are available, demonstrating its potential as a scalable and practical tool for studying phage-host interactions across the global phageome.

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arXiv2025

Computational approaches for virus host prediction: A review of methods and applications

Accurate prediction of virus-host interactions is critical for understanding viral ecology and developing applications like phage therapy. However, the growing number of computational tools has created a complex landscape, making direct performance comparison challenging due to inconsistent benchmarks and varying usability. Here, we provide a systematic review and a rigorous benchmark of 27 virus-host prediction tools. We formulate the host prediction task into two primary frameworks, link prediction and multi-class classification, and construct two benchmark datasets to evaluate tool performance in distinct scenarios: a database-centric dataset (RefSeq-VHDB) and a metagenomic discovery dataset (MetaHiC-VHDB). Our results reveal that no single tool is universally optimal. Performance is highly context-dependent, with tools like CHERRY and iPHoP demonstrating robust, broad applicability, while others, such as RaFAH and PHIST, excel in specific contexts. We further identify a critical trade-off between predictive accuracy, prediction rate, and computational cost. This work serves as a practical guide for researchers and establishes a standardized benchmark to drive future innovation in deciphering complex virus-host interactions.

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arXiv2025

ViralQC: A Tool for Assessing Completeness and Contamination of Predicted Viral Contigs

Motivation: Viruses represent the most abundant biological entities on the planet and play vital roles in diverse ecosystems. Cataloging viruses across various environments is essential for understanding their properties and functions. Metagenomic sequencing has emerged as the most comprehensive method for virus discovery, enabling the sequencing of all genetic materials, including viruses, from host or environmental samples. However, distinguishing viral sequences from the vast background of cellular organism-derived reads in metagenomic data remains a significant challenge. While several learning-based tools, such as VirSorter2 and geNomad, have shown promise in identifying viral contigs, they often experience varying degrees of false positive rates due to noise in sequencing and assembly, shared genes between viruses and their hosts, and the formation of proviruses within host genomes. This highlights the urgent need for an accurate and efficient method to evaluate the quality of viral contigs. Results: To address these challenges, we introduce ViralQC, a tool designed to assess the quality of reported viral contigs or bins. ViralQC identifies contamination regions within putative viral sequences using foundation models trained on viral and cellular genomes and estimates viral completeness through protein organization alignment. We evaluate ViralQC on multiple datasets and compare its performance against CheckV, the state-of-the-art in virus quality assessment. Notably, ViralQC correctly identifies 38% more contamination than CheckV, while maintaining a median absolute error of only 3%. In addition, ViralQC delivers more accurate results for medium- to high-quality (>50% completeness) contigs, demonstrating its superior performance in completeness estimation.

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arXiv2025

GiantHunter: Accurate detection of giant virus in metagenomic data using reinforcement-learning and Monte Carlo tree search

Motivation: Nucleocytoplasmic large DNA viruses (NCLDVs) are notable for their large genomes and extensive gene repertoires, which contribute to their widespread environmental presence and critical roles in processes such as host metabolic reprogramming and nutrient cycling. Metagenomic sequencing has emerged as a powerful tool for uncovering novel NCLDVs in environmental samples. However, identifying NCLDV sequences in metagenomic data remains challenging due to their high genomic diversity, limited reference genomes, and shared regions with other microbes. Existing alignment-based and machine learning methods struggle with achieving optimal trade-offs between sensitivity and precision. Results: In this work, we present GiantHunter, a reinforcement learning-based tool for identifying NCLDVs from metagenomic data. By employing a Monte Carlo tree search strategy, GiantHunter dynamically selects representative non-NCLDV sequences as the negative training data, enabling the model to establish a robust decision boundary. Benchmarking on rigorously designed experiments shows that GiantHunter achieves high precision while maintaining competitive sensitivity, improving the F1-score by 10% and reducing computational cost by 90% compared to the second-best method. To demonstrate its real-world utility, we applied GiantHunter to 60 metagenomic datasets collected from six cities along the Yangtze River, located both upstream and downstream of the Three Gorges Dam. The results reveal significant differences in NCLDV diversity correlated with proximity to the dam, likely influenced by reduced flow velocity caused by the dam. These findings highlight the potential of GiantSeeker to advance our understanding of NCLDVs and their ecological roles in diverse environments.

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arXiv2024

PhaGO: Protein function annotation for bacteriophages by integrating the genomic context

Bacteriophages are viruses that target bacteria, playing a crucial role in microbial ecology. Phage proteins are important in understanding phage biology, such as virus infection, replication, and evolution. Although a large number of new phages have been identified via metagenomic sequencing, many of them have limited protein function annotation. Accurate function annotation of phage proteins presents several challenges, including their inherent diversity and the scarcity of annotated ones. Existing tools have yet to fully leverage the unique properties of phages in annotating protein functions. In this work, we propose a new protein function annotation tool for phages by leveraging the modular genomic structure of phage genomes. By employing embeddings from the latest protein foundation models and Transformer to capture contextual information between proteins in phage genomes, PhaGO surpasses state-of-the-art methods in annotating diverged proteins and proteins with uncommon functions by 6.78% and 13.05% improvement, respectively. PhaGO can annotate proteins lacking homology search results, which is critical for characterizing the rapidly accumulating phage genomes. We demonstrate the utility of PhaGO by identifying 688 potential holins in phages, which exhibit high structural conservation with known holins. The results show the potential of PhaGO to extend our understanding of newly discovered phages.

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arXiv2024

SmoothGNN: Smoothing-aware GNN for Unsupervised Node Anomaly Detection

The smoothing issue in graph learning leads to indistinguishable node representations, posing significant challenges for graph-related tasks. However, our experiments reveal that this problem can uncover underlying properties of node anomaly detection (NAD) that previous research has missed. We introduce Individual Smoothing Patterns (ISP) and Neighborhood Smoothing Patterns (NSP), which indicate that the representations of anomalous nodes are harder to smooth than those of normal ones. In addition, we explore the theoretical implications of these patterns, demonstrating the potential benefits of ISP and NSP for NAD tasks. Motivated by these findings, we propose SmoothGNN, a novel unsupervised NAD framework. First, we design a learning component to explicitly capture ISP for detecting node anomalies. Second, we design a spectral graph neural network to implicitly learn ISP to enhance detection. Third, we design an effective coefficient based on our findings that NSP can serve as coefficients for node representations, aiding in the identification of anomalous nodes. Furthermore, we devise a novel anomaly measure to calculate loss functions and anomalous scores for nodes, reflecting the properties of NAD using ISP and NSP. Extensive experiments on 9 real datasets show that SmoothGNN outperforms the best rival by an average of 14.66% in AUC and 7.28% in Average Precision, with 75x running time speedup, validating the effectiveness and efficiency of our framework.

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arXiv2024

Accurate and efficient protein embedding using multi-teacher distillation learning

Motivation: Protein embedding, which represents proteins as numerical vectors, is a crucial step in various learning-based protein annotation/classification problems, including gene ontology prediction, protein-protein interaction prediction, and protein structure prediction. However, existing protein embedding methods are often computationally expensive due to their large number of parameters, which can reach millions or even billions. The growing availability of large-scale protein datasets and the need for efficient analysis tools have created a pressing demand for efficient protein embedding methods. Results: We propose a novel protein embedding approach based on multi-teacher distillation learning, which leverages the knowledge of multiple pre-trained protein embedding models to learn a compact and informative representation of proteins. Our method achieves comparable performance to state-of-the-art methods while significantly reducing computational costs and resource requirements. Specifically, our approach reduces computational time by ~70\% and maintains almost the same accuracy as the original large models. This makes our method well-suited for large-scale protein analysis and enables the bioinformatics community to perform protein embedding tasks more efficiently.

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arXiv2023

PhaBOX: A web server for identifying and characterizing phage contigs in metagenomic data

Motivation: There is accumulating evidence showing the important roles of bacteriophages (phages) in regulating the structure and functions of the microbiome. However, lacking an easy-to-use and integrated phage analysis software hampers microbiome-related research from incorporating phages in the analysis. Results: In this work, we developed a web server, PhaBOX, which can comprehensively identify and analyze phage contigs in metagenomic data. It supports integrated phage analysis, including phage contig identification from the metagenomic assembly, lifestyle prediction, taxonomic classification, and host prediction. Instead of treating the algorithms as a black box, PhaBOX also supports visualization of the essential features for making predictions. The web server is designed with a user-friendly graphical interface that enables both informatics-trained and non-specialist users to analyze phages in microbiome data with ease. Availability: The web server of PhaBOX is available via: https://phage.ee.cityu.edu.hk. The source code of PhaBOX is available at: https://github.com/KennthShang/PhaBOX Contact: yannisun@cityu.edu.hk

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arXiv2023

PhaVIP: Phage VIrion Protein classification based on chaos game representation and Vision Transformer

Motivation: As viruses that mainly infect bacteria, phages are key players across a wide range of ecosystems. Analyzing phage proteins is indispensable for understanding phages' functions and roles in microbiomes. High-throughput sequencing enables us to obtain phages in different microbiomes with low cost. However, compared to the fast accumulation of newly identified phages, phage protein classification remains difficult. In particular, a fundamental need is to annotate virion proteins, the structural proteins such as major tail, baseplate etc. Although there are experimental methods for virion protein identification, they are too expensive or time-consuming, leaving a large number of proteins unclassified. Thus, there is a great demand to develop a computational method for fast and accurate phage virion protein classification. Results: In this work, we adapted the state-of-the-art image classification model, Vision Transformer, to conduct virion protein classification. By encoding protein sequences into unique images using chaos gaming representation, we can leverage Vision Transformer to learn both local and global features from sequence ``images''. Our method, PhaVIP, has two main functions: classifying PVP and non-PVP sequences and annotating the types of PVP, such as capsid and tail. We tested PhaVIP on several datasets with increasing difficulty and benchmarked it against alternative tools. The experimental results show that PhaVIP has superior performance. After validating the performance of PhaVIP, we investigated two applications that can use the output of PhaVIP: phage taxonomy classification and phage host prediction. The results show the benefit of using classified proteins rather than all proteins.

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arXiv2022

Phage family classification under Caudoviricetes: a review of current tools using the latest ICTV classification framework

Bacteriophages, which are viruses infecting bacteria, are the most ubiquitous and diverse entities in the biosphere. There is accumulating evidence revealing their important roles in shaping the structure of various microbiomes. Thanks to (viral) metagenomic sequencing, a large number of new bacteriophages have been discovered. However, lacking a standard and automatic virus classification pipeline, the taxonomic characterization of new viruses seriously lag behind the sequencing efforts. In particular, according to the latest version of ICTV, several large phage families in the previous classification system are removed. Therefore, a comprehensive review and comparison of taxonomic classification tools under the new standard are needed to establish the state-of-the-art. In this work, we retrained and tested four recently published tools on newly labeled databases. We demonstrated their utilities and tested them on multiple datasets, including the RefSeq, short contigs, simulated metagenomic datasets, and low-similarity datasets. This study provides a comprehensive review of phage family classification in different scenarios and a practical guidance for choosing appropriate taxonomic classification pipelines. To our best knowledge, this is the first review conducted under the new ICTV classification framework. The results show that the new family classification framework overall leads to better-conserved groups and thus makes family-level classification more feasible.

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arXiv2022

PhaTYP: Predicting the lifestyle for bacteriophages using BERT

Bacteriophages (or phages), which infect bacteria, have two distinct lifestyles: virulent and temperate. Predicting the lifestyle of phages helps decipher their interactions with their bacterial hosts, aiding phages' applications in fields such as phage therapy. Because experimental methods for annotating the lifestyle of phages cannot keep pace with the fast accumulation of sequenced phages, computational method for predicting phages' lifestyles has become an attractive alternative. Despite some promising results, computational lifestyle prediction remains difficult because of the limited known annotations and the sheer amount of sequenced phage contigs assembled from metagenomic data. In particular, most of the existing tools cannot precisely predict phages' lifestyles for short contigs. In this work, we develop PhaTYP (Phage TYPe prediction tool) to improve the accuracy of lifestyle prediction on short contigs. We design two different training tasks, self-supervised and fine-tuning tasks, to overcome lifestyle prediction difficulties. We rigorously tested and compared PhaTYP with four state-of-the-art methods: DeePhage, PHACTS, PhagePred, and BACPHLIP. The experimental results show that PhaTYP outperforms all these methods and achieves more stable performance on short contigs. In addition, we demonstrated the utility of PhaTYP for analyzing the phage lifestyle on human neonates' gut data. This application shows that PhaTYP is a useful means for studying phages in metagenomic data and helps extend our understanding of microbial communities.

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arXiv2022

Accurate identification of bacteriophages from metagenomic data using Transformer

Motivation: Bacteriophages are viruses infecting bacteria. Being key players in microbial communities, they can regulate the composition/function of microbiome by infecting their bacterial hosts and mediating gene transfer. Recently, metagenomic sequencing, which can sequence all genetic materials from various microbiome, has become a popular means for new phage discovery. However, accurate and comprehensive detection of phages from the metagenomic data remains difficult. High diversity/abundance, and limited reference genomes pose major challenges for recruiting phage fragments from metagenomic data. Existing alignment-based or learning-based models have either low recall or precision on metagenomic data. Results: In this work, we adopt the state-of-the-art language model, Transformer, to conduct contextual embedding for phage contigs. By constructing a protein-cluster vocabulary, we can feed both the protein composition and the proteins' positions from each contig into the Transformer. The Transformer can learn the protein organization and associations using the self-attention mechanism and predicts the label for test contigs. We rigorously tested our developed tool named PhaMer on multiple datasets with increasing difficulty, including quality RefSeq genomes, short contigs, simulated metagenomic data, mock metagenomic data, and the public IMG/VR dataset. All the experimental results show that PhaMer outperforms the state-of-the-art tools. In the real metagenomic data experiment, PhaMer improves the F1-score of phage detection by 27\%.

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arXiv2022

CHERRY: a Computational metHod for accuratE pRediction of virus-pRokarYotic interactions using a graph encoder-decoder model

Prokaryotic viruses, which infect bacteria and archaea, are key players in microbial communities. Predicting the hosts of prokaryotic viruses helps decipher the dynamic relationship between microbes. Experimental methods for host prediction cannot keep pace with the fast accumulation of sequenced phages. Thus, there is a need for computational host prediction. Despite some promising results, computational host prediction remains a challenge because of the limited known interactions and the sheer amount of sequenced phages by high-throughput sequencing technologies. The state-of-the-art methods can only achieve 43\% accuracy at the species level. In this work, we formulate host prediction as link prediction in a knowledge graph that integrates multiple protein and DNA-based sequence features. Our implementation named CHERRY can be applied to predict hosts for newly discovered viruses and to identify viruses infecting targeted bacteria. We demonstrated the utility of CHERRY for both applications and compared its performance with 11 popular host prediction methods. To our best knowledge, CHERRY has the highest accuracy in identifying virus-prokaryote interactions. It outperforms all the existing methods at the species level with an accuracy increase of 37\%. In addition, CHERRY's performance on short contigs is more stable than other tools.

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arXiv2021

Predicting the hosts of prokaryotic viruses using GCN-based semi-supervised learning

Background: Prokaryotic viruses, which infect bacteria and archaea, are the most abundant and diverse biological entities in the biosphere. To understand their regulatory roles in various ecosystems and to harness the potential of bacteriophages for use in therapy, more knowledge of viral-host relationships is required. High-throughput sequencing and its application to the microbiome have offered new opportunities for computational approaches for predicting which hosts particular viruses can infect. However, there are two main challenges for computational host prediction. First, the empirically known virus-host relationships are very limited. Second, although sequence similarity between viruses and their prokaryote hosts have been used as a major feature for host prediction, the alignment is either missing or ambiguous in many cases. Thus, there is still a need to improve the accuracy of host prediction. Results: In this work, we present a semi-supervised learning model, named HostG, to conduct host prediction for novel viruses. We construct a knowledge graph by utilizing both virus-virus protein similarity and virus-host DNA sequence similarity. Then graph convolutional network (GCN) is adopted to exploit viruses with or without known hosts in training to enhance the learning ability. During the GCN training, we minimize the expected calibrated error (ECE) to ensure the confidence of the predictions. We tested HostG on both simulated and real sequencing data and compared its performance with other state-of-the-art methods specifcally designed for virus host classification (VHM-net, WIsH, PHP, HoPhage, RaFAH, vHULK, and VPF-Class). Conclusion: HostG outperforms other popular methods, demonstrating the efficacy of using a GCN-based semi-supervised learning approach. A particular advantage of HostG is its ability to predict hosts from new taxa.

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arXiv2021

Bacteriophage classification for assembled contigs using Graph Convolutional Network

Motivation: Bacteriophages (aka phages), which mainly infect bacteria, play key roles in the biology of microbes. As the most abundant biological entities on the planet, the number of discovered phages is only the tip of the iceberg. Recently, many new phages have been revealed using high throughput sequencing, particularly metagenomic sequencing. Compared to the fast accumulation of phage-like sequences, there is a serious lag in taxonomic classification of phages. High diversity, abundance, and limited known phages pose great challenges for taxonomic analysis. In particular, alignment-based tools have difficulty in classifying fast accumulating contigs assembled from metagenomic data. Results: In this work, we present a novel semi-supervised learning model, named PhaGCN, to conduct taxonomic classification for phage contigs. In this learning model, we construct a knowledge graph by combining the DNA sequence features learned by convolutional neural network (CNN) and protein sequence similarity gained from gene-sharing network. Then we apply graph convolutional network (GCN) to utilize both the labeled and unlabeled samples in training to enhance the learning ability. We tested PhaGCN on both simulated and real sequencing data. The results clearly show that our method competes favorably against available phage classification tools.

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arXiv2020

ProDOMA: improve PROtein DOMAin classification for third-generation sequencing reads using deep learning

Motivation: With the development of third-generation sequencing technologies, people are able to obtain DNA sequences with lengths from 10s to 100s of kb. These long reads allow protein domain annotation without assembly, thus can produce important insights into the biological functions of the underlying data. However, the high error rate in third-generation sequencing data raises a new challenge to established domain analysis pipelines. The state-of-the-art methods are not optimized for noisy reads and have shown unsatisfactory accuracy of domain classification in third-generation sequencing data. New computational methods are still needed to improve the performance of domain prediction in long noisy reads. Results: In this work, we introduce ProDOMA, a deep learning model that conducts domain classification for third-generation sequencing reads. It uses deep neural networks with 3-frame translation encoding to learn conserved features from partially correct translations. In addition, we formulate our problem as an open-set problem and thus our model can reject unrelated DNA reads such as those from noncoding regions. In the experiments on simulated reads of protein coding sequences and real reads from the human genome, our model outperforms HMMER and DeepFam on protein domain classification. In summary, ProDOMA is a useful end-to-end protein domain analysis tool for long noisy reads without relying on error correction. Availability: The source code and the trained model are freely available at https://github.com/strideradu/ProDOMA. Contact: yannisun@cityu.edu.hk

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