IEEE/ACM Transactions on Computational Biology and Bioinformatics最新文献

As a central organizing principle of biology, bacteria and archaea are classified into a hierarchical structure across taxonomic ranks from kingdom to subspecies. Traditionally, this organization was based on observable characteristics of form and chemistry but recently, bacterial taxonomy has been robustly quantified using comparisons of sequenced genomes, as exemplified in the Genome Taxonomy Database (GTDB). Such genome-based taxonomies resolve genomes down to genera and species and are useful in many contexts yet lack the flexibility and resolution of a fine-grained approach. The Life Identification Number (LIN) approach is a common, quantitative framework to tie existing (and future) bacterial taxonomies together, increase the resolution of genome-based discrimination of taxa, and extend taxonomic identification below the species level in a principled way. Utilizing LINgroup as an organizational concept helps resolve some of the confusion and unforeseen negative effects resulting from nomenclature changes of microorganisms that are closely related by overall genomic similarity (often due to genome-based reclassification). Our experimental results demonstrate the value of LINs and LINgroups in mapping between taxonomies, translating between different nomenclatures, and integrating them into a single taxonomic framework. They also reveal the robustness of LIN assignment to hyper-parameter changes when considering within-species taxonomic groups.

In this paper, we propose a Learning-based gEnome Codec (LEC), which is designed for high efficiency and enhanced flexibility. The LEC integrates several advanced technologies, including Group of Bases (GoB) compression, multi-stride coding and bidirectional prediction, all of which are aimed at optimizing the balance between coding complexity and performance in lossless compression. The model applied in our proposed codec is data-driven, based on deep neural networks to infer probabilities for each symbol, enabling fully parallel encoding and decoding with configured complexity for diverse applications. Based upon a set of configurations on compression ratios and inference speed, experimental results show that the proposed method is very efficient in terms of compression performance and provides improved flexibility in real-world applications.

Tensor Canonical Correlation Analysis (TCCA) is a commonly employed statistical method utilized to examine linear associations between two sets of tensor datasets. However, the existing TCCA models fail to adequately address the heterogeneity present in real-world tensor data, such as brain imaging data collected from diverse groups characterized by factors like sex and race. Consequently, these models may yield biased outcomes. In order to surmount this constraint, we propose a novel approach called Multi-Group TCCA (MG-TCCA), which enables the joint analysis of multiple subgroups. By incorporating a dual sparsity structure and a block coordinate ascent algorithm, our MG-TCCA method effectively addresses heterogeneity and leverages information across different groups to identify consistent signals. This novel approach facilitates the quantification of shared and individual structures, reduces data dimensionality, and enables visual exploration. To empirically validate our approach, we conduct a study focused on investigating correlations between two brain positron emission tomography (PET) modalities (AV-45 and FDG) within an Alzheimer's disease (AD) cohort. Our results demonstrate that MG-TCCA surpasses traditional TCCA and Sparse TCCA (STCCA) in identifying sex-specific cross-modality imaging correlations. This heightened performance of MG-TCCA provides valuable insights for the characterization of multimodal imaging biomarkers in AD.

Recent advancements in spatially transcriptomics (ST) technologies have enabled the comprehensive measurement of gene expression profiles while preserving the spatial information of cells. Combining gene expression profiles and spatial information has been the most commonly used method to identify spatial functional domains and genes. However, most existing spatial domain decipherer methods are more focused on spatially neighboring structures and fail to take into account balancing the self-characteristics and the spatial structure dependency of spots. Therefore, we propose a novel model called SpaGCAC, which recognizes spatial domains with the help of an adaptive feature-spatial balanced graph convolutional network named AFSBGCN. The AFSBGCN can dynamically learn the relationship between spatial local topology structures and the self-characteristics of spots by adaptively increasing or declining the weight on the self-characteristics during message aggregation. Moreover, to better capture the local structures of spots, SpaGCAC exploits a local topology structure contrastive learning strategy. Meanwhile, SpaGCAC utilizes a probability distribution contrastive learning strategy to increase the similarity of probability distributions for points belonging to the same category. We validate the performance of SpaGCAC for spatial domain identification on four spatial transcriptomic datasets. In comparison with seven spatial domain recognition methods, SpaGCAC achieved the highest NMI median of 0.683 and the second highest ARI median of 0.559 on the multi-slice DLPFC dataset. SpaGCAC achieved the best results on all three other single-slice datasets. The above-mentioned results show that SpaGCAC outperforms most existing methods, providing enhanced insights into tissue heterogeneity.

Models for microbial interactions attempt to understand and predict the steady state network of inter-species relationships in a community, e.g. competition for shared metabolites, and cooperation through cross-feeding. Flux balance analysis (FBA) is an approach that was introduced to model the interaction of a particular microbial species with its environment. This approach has been extended to analyzing interactions in a community of microbes; however, these approaches have two important drawbacks: first, one has to numerically solve a differential equation to identify the steady state, and second, there are no methods available to analyze the stability of the steady state. We propose a game theory based community FBA model wherein species compete to maximize their individual growth rate, and the state of the community is given by the resulting Nash equilibrium. We develop a computationally efficient method for directly computing the steady state biomasses and fluxes without solving a differential equation. We also develop a method to determine the stability of a steady state to perturbations in the biomasses and to invasion by new species. We report the results of applying our proposed framework to a small community of four E. coli mutants that compete for externally supplied glucose, as well as cooperate since the mutants are auxotrophic for metabolites exported by other mutants, and a more realistic model for a gut microbiome consisting of nine species.

Drug Target Interaction (DTI) prediction plays a crucial role in in-silico drug discovery, especially for deep learning (DL) models. Along this line, existing methods usually first extract features from drugs and target proteins, and use drug-target pairs to train DL models. However, these DL-based methods essentially rely on similar structures and patterns defined by the homologous proteins from a large amount of data. When few drug-target interactions are known for a newly discovered protein and its homologous proteins, prediction performance can suffer notable reduction. In this paper, we propose a novel Protein-Context enhanced Master/Slave Framework (PCMS), for zero-shot DTI prediction. This framework facilitates the efficient discovery of ligands for newly discovered target proteins, addressing the challenge of predicting interactions without prior data. Specifically, the PCMS framework consists of two main components: a Master Learner and a Slave Learner. The Master Learner first learns the target protein context information, and then adaptively generates the corresponding parameters for the Slave Learner. The Slave Learner then perform zero-shot DTI prediction in different protein contexts. Extensive experiments verify the effectiveness of our PCMS compared to state-of-the-art methods in various metrics on two public datasets. The Code and the processed Data will be open once the paper is accepted.

Apple leaf diseases can seriously affect apple production and quality, and accurately detecting them can improve the efficiency of disease monitoring. Owing to the complex natural growth environment, apple leaf lesions may be easily confused with background noise, leading to poor performance. In this study, a cascaded Incremental Region Proposal Network (Inc-RPN) is proposed to accurately detect apple leaf diseases in natural environments. The proposed Inc-RPN has a two-layer RPN architecture, where the precursor RPN is leveraged to generate diseased leaf proposals, and the successor RPN focuses on extracting target disease spots based on diseased leaf proposals. In the successor RPN, a low-level feature aggregation module is designed to fully utilize the bridged features and preserve the semantic information of the target disease spots. An incremental module is also leveraged to extract aggregated diseased leaf features and target disease spot features. Finally, a novel position anchor generator is designed to generate anchors based on diseased leaf proposals. The experimental results show that the proposed Inc-RPN performs very well on the FALD_CED and Apple Leaf Disease datasets, showing that it can accurately perform apple leaf disease detection tasks.

AutoDock Vina and its derivatives have established themselves as a prevailing pipeline for virtual screening in contemporary drug discovery. Our Vina-GPU method leverages the parallel computing power of GPUs to accelerate AutoDock Vina, and Vina-GPU 2.0 further enhances the speed of AutoDock Vina and its derivatives. Given the prevalence of large virtual screens in modern drug discovery, the improvement of speed and accuracy in virtual screening has become a longstanding challenge. In this study, we propose Vina-GPU 2.1, aimed at enhancing the docking speed and precision of AutoDock Vina and its derivatives through the integration of novel algorithms to facilitate improved docking and virtual screening outcomes. Building upon the foundations laid by Vina-GPU 2.0, we introduce a novel algorithm, namely Reduced Iteration and Low Complexity BFGS (RILC-BFGS), designed to expedite the most time-consuming operation. Additionally, we implement grid cache optimization to further enhance the docking speed. Furthermore, we employ optimal strategies to individually optimize the structures of ligands, receptors, and binding pockets, thereby enhancing the docking precision. To assess the performance of Vina-GPU 2.1, we conduct extensive virtual screening experiments on three prominent targets, utilizing two fundamental compound libraries and seven docking tools. Our results demonstrate that Vina-GPU 2.1 achieves an average 4.97-fold acceleration in docking speed and an average 342% improvement in EF1% compared to Vina-GPU 2.0. The source code and tools for Vina-GPU 2.1 are freely available accompanied by comprehensive instructions and illustrative examples.

Protein-metal ion interactions play a central role in the onset of numerous diseases. When amino acid changes lead to missense mutations in metal-binding sites, the disrupted interaction with metal ions can compromise protein function, potentially causing severe human ailments. Identifying these disease-associated mutation sites within metal-binding regions is paramount for understanding protein function and fostering innovative drug development. While some computational methods aim to tackle this challenge, they often fall short in accuracy, commonly due to manual feature extraction and the absence of structural data. We introduce MetalPrognosis, an innovative, alignment-free solution that predicts disease-associated mutations within metal-binding sites of metalloproteins with heightened precision. Rather than relying on manual feature extraction, MetalPrognosis employs sliding window sequences as input, extracting deep semantic insights from pre-trained protein language models. These insights are then incorporated into a convolutional neural network, facilitating the derivation of intricate features. Comparative evaluations show MetalPrognosis outperforms leading methodologies like MCCNN and M-Ionic across various metalloprotein test sets. Furthermore, an ablation study reiterates the effectiveness of our model architecture. To facilitate public use, we have made the datasets, source codes, and trained models for MetalPrognosis online available at http://metalprognosis.unimelb-biotools.cloud.edu.au/.

Alignment-free analysis of sequences has revolutionized the high-throughput processing of sequencing data within numerous bioinformatics pipelines. Hashing k-mers represents a common function across various alignment-free applications, serving as a crucial tool for indexing, querying, and rapid similarity searching. More recently, spaced seeds, a specialized pattern that accommodates errors or mutations, have become a standard choice over traditional k-mers. Spaced seeds offer enhanced sensitivity in many applications when compared to k-mers. However, it's important to note that hashing spaced seeds significantly increases computational time. Furthermore, if multiple spaced seeds are employed, accuracy can be further improved, albeit at the expense of longer processing times. This paper addresses the challenge of efficiently hashing multiple spaced seeds. The proposed algorithms leverage the similarity of adjacent spaced seed hash values within an input sequence, allowing for the swift computation of subsequent hashes. Our experimental results, conducted across various tests, demonstrate a remarkable performance improvement over previously suggested algorithms, with potential speedups of up to 20 times. Additionally, we apply these efficient spaced seed hashing algorithms to a metagenomic application, specifically the classification of reads using Clark-S [Ounit and Lonardi, 2016]. Our findings reveal a substantial speedup, effectively mitigating the slowdown caused by the utilization of multiple spaced seeds.