Briefings in bioinformatics最新文献

{"title":"TriTan: an efficient triple nonnegative matrix factorization method for integrative analysis of single-cell multiomics data.","authors":"Xin Ma, Lijing Lin, Qian Zhao, Mudassar Iqbal","doi":"10.1093/bib/bbae615","DOIUrl":"10.1093/bib/bbae615","url":null,"abstract":"<p><p>Single-cell multiomics have opened up tremendous opportunities for understanding gene regulatory networks underlying cell states by simultaneously profiling transcriptomes, epigenomes, and proteomes of the same cell. However, existing computational methods for integrative analysis of these high-dimensional multiomics data are either computationally expensive or limited in interpretation. These limitations pose challenges in the implementation of these methods in large-scale studies and hinder a more in-depth understanding of the underlying regulatory mechanisms. Here, we propose TriTan (Triple inTegrative fast non-negative matrix factorization), an efficient joint factorization method for single-cell multiomics data. TriTan implements a highly efficient factorization algorithm, greatly improving its computational performance. Three matrix factorization produced by TriTan helps in clustering cells, identifying signature features for each cell type, and uncovering feature associations across omics, which facilitates the identification of domains of regulatory chromatin and the prediction of cell-type-specific regulatory networks. We applied TriTan to the single-cell multiomics data obtained from different technologies and benchmarked it against the state-of-the-art methods where it shows highly competitive performance. Furthermore, we showed a range of downstream analyses conducted utilizing TriTan outputs, highlighting its capacity to facilitate interpretation in biological discovery.</p>","PeriodicalId":9209,"journal":{"name":"Briefings in bioinformatics","volume":"26 1","pages":""},"PeriodicalIF":6.8,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11586128/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142709258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miCGR: interpretable deep neural network for predicting both site-level and gene-level functional targets of microRNA.","authors":"Xiaolong Wu, Lehan Zhang, Xiaochu Tong, Yitian Wang, Zimei Zhang, Xiangtai Kong, Shengkun Ni, Xiaomin Luo, Mingyue Zheng, Yun Tang, Xutong Li","doi":"10.1093/bib/bbae616","DOIUrl":"10.1093/bib/bbae616","url":null,"abstract":"<p><p>MicroRNAs (miRNAs) are critical regulators in various biological processes to cleave or repress translation of messenger RNAs (mRNAs). Accurately predicting miRNA targets is essential for developing miRNA-based therapies for diseases such as cancer and cardiovascular disease. Traditional miRNA target prediction methods often struggle due to incomplete knowledge of miRNA-target interactions and lack interpretability. To address these limitations, we propose miCGR, an end-to-end deep learning framework for predicting functional miRNA targets. MiCGR employs 2D convolutional neural networks alongside an enhanced Chaos Game Representation (CGR) of both miRNA sequences and their candidate target site (CTS) on mRNA. This advanced CGR transforms genetic sequences into informative 2D graphical representations based on sequence composition and subsequence frequencies, and explicitly incorporates important prior knowledge of seed regions and subsequence positions. Unlike one-dimensional methods based solely on sequence characters, this approach identifies functional motifs within sequences, even if they are distant in the original sequences. Our model outperforms existing methods in predicting functional targets at both the site and gene levels. To enhance interpretability, we incorporate Shapley value analysis for each subsequence within both miRNA sequences and their target sites, allowing miCGR to achieve improved accuracy, particularly with more lenient CTS selection criteria. Finally, two case studies demonstrate the practical applicability of miCGR, highlighting its potential to provide insights for optimizing artificial miRNA analogs that surpass endogenous counterparts.</p>","PeriodicalId":9209,"journal":{"name":"Briefings in bioinformatics","volume":"26 1","pages":""},"PeriodicalIF":6.8,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11596087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142726304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"UPicker: a semi-supervised particle picking transformer method for cryo-EM micrographs.","authors":"Chi Zhang, Yiran Cheng, Kaiwen Feng, Fa Zhang, Renmin Han, Jieqing Feng","doi":"10.1093/bib/bbae636","DOIUrl":"10.1093/bib/bbae636","url":null,"abstract":"<p><p>Automatic single particle picking is a critical step in the data processing pipeline of cryo-electron microscopy structure reconstruction. In recent years, several deep learning-based algorithms have been developed, demonstrating their potential to solve this challenge. However, current methods highly depend on manually labeled training data, which is labor-intensive and prone to biases especially for high-noise and low-contrast micrographs, resulting in suboptimal precision and recall. To address these problems, we propose UPicker, a semi-supervised transformer-based particle-picking method with a two-stage training process: unsupervised pretraining and supervised fine-tuning. During the unsupervised pretraining, an Adaptive Laplacian of Gaussian region proposal generator is proposed to obtain pseudo-labels from unlabeled data for initial feature learning. For the supervised fine-tuning, UPicker only needs a small amount of labeled data to achieve high accuracy in particle picking. To further enhance model performance, UPicker employs a contrastive denoising training strategy to reduce redundant detections and accelerate convergence, along with a hybrid data augmentation strategy to deal with limited labeled data. Comprehensive experiments on both simulated and experimental datasets demonstrate that UPicker outperforms state-of-the-art particle-picking methods in terms of accuracy and robustness while requiring fewer labeled data than other transformer-based models. Furthermore, ablation studies demonstrate the effectiveness and necessity of each component of UPicker. The source code and data are available at https://github.com/JachyLikeCoding/UPicker.</p>","PeriodicalId":9209,"journal":{"name":"Briefings in bioinformatics","volume":"26 1","pages":""},"PeriodicalIF":6.8,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631311/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Precise identification of somatic and germline variants in the absence of matched normal samples.","authors":"Hui Li, Lu Meng, Hongke Wang, Liang Cui, Heyu Sheng, Peiyan Zhao, Shuo Hong, Xinhua Du, Shi Yan, Yun Xing, Shicheng Feng, Yan Zhang, Huan Fang, Jing Bai, Yan Liu, Shaowei Lan, Tao Liu, Yanfang Guan, Xuefeng Xia, Xin Yi, Ying Cheng","doi":"10.1093/bib/bbae677","DOIUrl":"10.1093/bib/bbae677","url":null,"abstract":"<p><p>Somatic variants play a crucial role in the occurrence and progression of cancer. However, in the absence of matched normal controls, distinguishing between germline and somatic variants becomes challenging in tumor samples. The existing tumor-only genomic analysis methods either suffer from limited performance or insufficient interpretability due to an excess of features. Therefore, there is an urgent need for an alternative approach that can address these issues and have practical implications. Here, we presented OncoTOP, a computational method for genomic analysis without matched normal samples, which can accurately distinguish somatic mutations from germline variants. Reference sample analysis revealed a 0% false positive rate and 99.7% reproducibility for variant calling. Assessing 2864 tumor samples across 18 cancer types yielded a 99.8% overall positive percent agreement and a 99.9% positive predictive value. OncoTOP can also accurately detect clinically actionable variants and subclonal mutations associated with drug resistance. For the prediction of mutation origins, the positive percent agreement stood at 97.4% for predicting somatic mutations and 95.7% for germline mutations. High consistency of tumor mutational burden (TMB) was observed between the results generated by OncoTOP and tumor-normal paired analysis. In a cohort of 97 lung cancer patients treated with immunotherapy, TMB-high patients had prolonged PFS (P = .02), proving the reliability of our approach in estimating TMB to predict therapy response. Furthermore, microsatellite instability status showed a strong concordance (97%) with polymerase chain reaction results, and leukocyte antigens class I subtypes and homozygosity achieved an impressive concordance rate of 99.3% and 99.9% respectively, compared to its tumor-normal paired analysis. Thus, OncoTOP exhibited high reliability in variant calling, mutation origin prediction, and biomarker estimation. Its application will promise substantial advantages for clinical genomic testing.</p>","PeriodicalId":9209,"journal":{"name":"Briefings in bioinformatics","volume":"26 1","pages":""},"PeriodicalIF":6.8,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11684894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142906167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A comprehensive benchmark study of methods for identifying significantly perturbed subnetworks in cancer.","authors":"Le Yang, Runpu Chen, Steve Goodison, Yijun Sun","doi":"10.1093/bib/bbae692","DOIUrl":"10.1093/bib/bbae692","url":null,"abstract":"<p><p>Network-based methods utilize protein-protein interaction information to identify significantly perturbed subnetworks in cancer and to propose key molecular pathways. Numerous methods have been developed, but to date, a rigorous benchmark analysis to compare the performance of existing approaches is lacking. In this paper, we proposed a novel benchmarking framework using synthetic data and conducted a comprehensive analysis to investigate the ability of existing methods to detect target genes and subnetworks and to control false positives, and how they perform in the presence of topological biases at both gene and subnetwork levels. Our analysis revealed insights into algorithmic performance that were previously unattainable. Based on the results of the benchmark study, we presented a practical guide for users on how to select appropriate detection methods and protein-protein interaction networks for cancer pathway identification, and provided suggestions for future algorithm development.</p>","PeriodicalId":9209,"journal":{"name":"Briefings in bioinformatics","volume":"26 1","pages":""},"PeriodicalIF":6.8,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11684898/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142906223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CDCM: a correlation-dependent connectivity map approach to rapidly screen drugs during outbreaks of infectious diseases.","authors":"Junlei Liao, Hongyang Yi, Hao Wang, Sumei Yang, Duanmei Jiang, Xin Huang, Mingxia Zhang, Jiayin Shen, Hongzhou Lu, Yuanling Niu","doi":"10.1093/bib/bbae659","DOIUrl":"10.1093/bib/bbae659","url":null,"abstract":"<p><p>In the context of the global damage caused by coronavirus disease 2019 (COVID-19) and the emergence of the monkeypox virus (MPXV) outbreak as a public health emergency of international concern, research into methods that can rapidly test potential therapeutics during an outbreak of a new infectious disease is urgently needed. Computational drug discovery is an effective way to solve such problems. The existence of various large open databases has mitigated the time and resource consumption of traditional drug development and improved the speed of drug discovery. However, the diversity of cell lines used in various databases remains limited, and previous drug discovery methods are ineffective for cross-cell prediction. In this study, we propose a correlation-dependent connectivity map (CDCM) to achieve cross-cell predictions of drug similarity. The CDCM mainly identifies drug-drug or disease-drug relationships from the perspective of gene networks by exploring the correlation changes between genes and identifying similarities in the effects of drugs or diseases on gene expression. We validated the CDCM on multiple datasets and found that it performed well for drug identification across cell lines. A comparison with the Connectivity Map revealed that our method was more stable and performed better across different cell lines. In the application of the CDCM to COVID-19 and MPXV data, the predictions of potential therapeutic compounds for COVID-19 were consistent with several previous studies, and most of the predicted drugs were found to be experimentally effective against MPXV. This result confirms the practical value of the CDCM. With the ability to predict across cell lines, the CDCM outperforms the Connectivity Map, and it has wider application prospects and a reduced cost of use.</p>","PeriodicalId":9209,"journal":{"name":"Briefings in bioinformatics","volume":"26 1","pages":""},"PeriodicalIF":6.8,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11658818/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A transformer-based deep learning survival prediction model and an explainable XGBoost anti-PD-1/PD-L1 outcome prediction model based on the cGAS-STING-centered pathways in hepatocellular carcinoma.","authors":"Ren Wang, Qiumei Liu, Wenhua You, Huiyu Wang, Yun Chen","doi":"10.1093/bib/bbae686","DOIUrl":"10.1093/bib/bbae686","url":null,"abstract":"<p><p>Recent studies suggest cGAS-STING pathway may play a crucial role in the genesis and development of hepatocellular carcinoma (HCC), closely associated with classical pathways and tumor immunity. We aimed to develop models predicting survival and anti-PD-1/PD-L1 outcomes centered on the cGAS-STING pathway in HCC. We identified classical pathways highly correlated with cGAS-STING pathway and constructed transformer survival model preserving raw structure of pathways. We also developed explainable XGBoost model for predicting anti-PD-1/PD-L1 outcomes using SHAP algorithm. We trained and validated transformer survival model on pan-cancer cohort and tested it on three independent HCC cohorts. Using 0.5 as threshold across cohorts, we divided each HCC cohort into two groups and calculated P values with log-rank test. TCGA-LIHC: C-index = 0.750, P = 1.52e-11; ICGC-LIRI-JP: C-index = 0.741, P = .00138; GSE144269: C-index = 0.647, P = .0233. We trained and validated [area under the receiver operating characteristic curve (AUC) = 0.777] XGBoost model on immunotherapy datasets and tested it on GSE78220 (AUC = 0.789); we also tested XGBoost model on HCC anti-PD-L1 cohort (AUC = 0.719). Our deep learning model and XGBoost model demonstrate potential in predicting survival risks and anti-PD-1/PD-L1 outcomes in HCC. We deployed these two prediction models to the GitHub repository and provided detailed instructions for their usage: deep learning survival model, https://github.com/mlwalker123/CSP_survival_model; XGBoost immunotherapy model, https://github.com/mlwalker123/CSP_immunotherapy_model.</p>","PeriodicalId":9209,"journal":{"name":"Briefings in bioinformatics","volume":"26 1","pages":""},"PeriodicalIF":6.8,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11695900/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ET-PROTACs: modeling ternary complex interactions using cross-modal learning and ternary attention for accurate PROTAC-induced degradation prediction.","authors":"Lijun Cai, Guanyu Yue, Yifan Chen, Li Wang, Xiaojun Yao, Quan Zou, Xiangzheng Fu, Dongsheng Cao","doi":"10.1093/bib/bbae654","DOIUrl":"10.1093/bib/bbae654","url":null,"abstract":"<p><strong>Motivation: </strong>Accurately predicting the degradation capabilities of proteolysis-targeting chimeras (PROTACs) for given target proteins and E3 ligases is important for PROTAC design. The distinctive ternary structure of PROTACs presents a challenge to traditional drug-target interaction prediction methods, necessitating more innovative approaches. While current state-of-the-art (SOTA) methods using graph neural networks (GNNs) can discern the molecular structure of PROTACs and proteins, thus enabling the efficient prediction of PROTACs' degradation capabilities, they rely heavily on limited crystal structure data of the POI-PROTAC-E3 ternary complex. This reliance underutilizes rich PROTAC experimental data and neglects intricate interaction relationships within ternary complexes.</p><p><strong>Results: </strong>In this study, we propose a model based on cross-modal strategy and ternary attention technology, ET-PROTACs, to predict the targeted degradation capabilities of PROTACs. Our model capitalizes on the strengths of cross-modal methods by using equivariant GNN graph neural networks to process the graph structure and spatial coordinates of PROTAC molecules concurrently while utilizing sequence-based methods to learn the protein sequence information. This integration of cross-modal information is cohesively harnessed and channeled into a ternary attention mechanism, specially tailored for the unique structure of PROTACs, enabling the congruent modeling of both PROTAC and protein modalities. Experimental results demonstrate that the ET-PROTACs model outperforms existing SOTA methods. Moreover, visualizing attention scores illuminates crucial residues and atoms pivotal in specific POI-PROTAC-E3 interactions, thus offering invaluable insights and guidance for future pharmaceutical research.</p><p><strong>Availability and implementation: </strong>The codes of our model are available at https://github.com/GuanyuYue/ET-PROTACs.</p>","PeriodicalId":9209,"journal":{"name":"Briefings in bioinformatics","volume":"26 1","pages":""},"PeriodicalIF":6.8,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11713031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142944791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multimodal deep learning approaches for precision oncology: a comprehensive review.","authors":"Huan Yang, Minglei Yang, Jiani Chen, Guocong Yao, Quan Zou, Linpei Jia","doi":"10.1093/bib/bbae699","DOIUrl":"https://doi.org/10.1093/bib/bbae699","url":null,"abstract":"<p><p>The burgeoning accumulation of large-scale biomedical data in oncology, alongside significant strides in deep learning (DL) technologies, has established multimodal DL (MDL) as a cornerstone of precision oncology. This review provides an overview of MDL applications in this field, based on an extensive literature survey. In total, 651 articles published before September 2024 are included. We first outline publicly available multimodal datasets that support cancer research. Then, we discuss key DL training methods, data representation techniques, and fusion strategies for integrating multimodal data. The review also examines MDL applications in tumor segmentation, detection, diagnosis, prognosis, treatment selection, and therapy response monitoring. Finally, we critically assess the limitations of current approaches and propose directions for future research. By synthesizing current progress and identifying challenges, this review aims to guide future efforts in leveraging MDL to advance precision oncology.</p>","PeriodicalId":9209,"journal":{"name":"Briefings in bioinformatics","volume":"26 1","pages":""},"PeriodicalIF":6.8,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multimodal multiobjective optimization with structural network control principles to optimize personalized drug targets for drug discovery of individual patients.","authors":"Jing Liang, Zhuo Hu, Ying Bi, Han Cheng, Wei-Feng Guo","doi":"10.1093/bib/bbaf007","DOIUrl":"10.1093/bib/bbaf007","url":null,"abstract":"<p><p>Structural network control principles provided novel and efficient clues for the optimization of personalized drug targets (PDTs) related to state transitions of individual patients. However, most existing methods focus on one subnetwork or module as drug targets through the identification of the minimal set of driver nodes and ignore the state transition capabilities of other modules with different configurations of drug targets [i.e. multimodal drug targets (MDTs)] embedding the knowledge of previous drug targets (i.e. multiobjective optimization). Therefore, a novel multimodal multiobjective evolutionary optimization framework (called MMONCP) is proposed to optimize PDTs with network control principles. The key points of MMONCP are that a constrained multimodal multiobjective optimization problem is formed with discrete constraints on the decision space and multimodality characteristics, and a novel evolutionary algorithm denoted as CMMOEA-GLS-WSCD is designed by combining a global and local search strategy and a weighting-based special crowding distance strategy to balance the diversity of both objective and decision space. The experimental results on three cancer genomics data from The Cancer Genome Atlas indicate that MMONCP achieves a higher performance including algorithm convergence and diversity, the fraction of identified MDTs, and the area under the curve score than advanced algorithms. Additionally, MMONCP can detect the early state from the difference between the target activity and toxicity of MDTs and provide early treatment options for cancer treatment in precision medicine.</p>","PeriodicalId":9209,"journal":{"name":"Briefings in bioinformatics","volume":"26 1","pages":""},"PeriodicalIF":6.8,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11747759/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}