arXiv subjects

Jiaojiao Guan

Publications and source records attributed to Jiaojiao Guan.

7 recordsLinked to original sources

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.

q-bio.GN↗

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.

q-bio.GN↗

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.

q-bio.GN↗

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.

q-bio.GN↗

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.

q-bio.GN↗

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.

q-bio.QM↗

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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