Briefings in bioinformatics最新文献

{"title":"BayeSMART: Bayesian clustering of multi-sample spatially resolved transcriptomics data.","authors":"Yanghong Guo, Bencong Zhu, Chen Tang, Ruichen Rong, Ying Ma, Guanghua Xiao, Lin Xu, Qiwei Li","doi":"10.1093/bib/bbae524","DOIUrl":"10.1093/bib/bbae524","url":null,"abstract":"<p><p>The field of spatially resolved transcriptomics (SRT) has greatly advanced our understanding of cellular microenvironments by integrating spatial information with molecular data collected from multiple tissue sections or individuals. However, methods for multi-sample spatial clustering are lacking, and existing methods primarily rely on molecular information alone. This paper introduces BayeSMART, a Bayesian statistical method designed to identify spatial domains across multiple samples. BayeSMART leverages artificial intelligence (AI)-reconstructed single-cell level information from the paired histology images of multi-sample SRT datasets while simultaneously considering the spatial context of gene expression. The AI integration enables BayeSMART to effectively interpret the spatial domains. We conducted case studies using four datasets from various tissue types and SRT platforms, and compared BayeSMART with alternative multi-sample spatial clustering approaches and a number of state-of-the-art methods for single-sample SRT analysis, demonstrating that it surpasses existing methods in terms of clustering accuracy, interpretability, and computational efficiency. BayeSMART offers new insights into the spatial organization of cells in multi-sample SRT data.</p>","PeriodicalId":9209,"journal":{"name":"Briefings in bioinformatics","volume":"25 6","pages":""},"PeriodicalIF":6.8,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11514062/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520980","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":"Semi-supervised learning with pseudo-labeling compares favorably with large language models for regulatory sequence prediction.","authors":"Han Phan, Céline Brouard, Raphaël Mourad","doi":"10.1093/bib/bbae560","DOIUrl":"10.1093/bib/bbae560","url":null,"abstract":"<p><p>Predicting molecular processes using deep learning is a promising approach to provide biological insights for non-coding single nucleotide polymorphisms identified in genome-wide association studies. However, most deep learning methods rely on supervised learning, which requires DNA sequences associated with functional data, and whose amount is severely limited by the finite size of the human genome. Conversely, the amount of mammalian DNA sequences is growing exponentially due to ongoing large-scale sequencing projects, but in most cases without functional data. To alleviate the limitations of supervised learning, we propose a novel semi-supervised learning (SSL) based on pseudo-labeling, which allows to exploit unlabeled DNA sequences from numerous genomes during model pre-training. We further improved it incorporating principles from the Noisy Student algorithm to predict the confidence in pseudo-labeled data used for pre-training, which showed improvements for transcription factor with very few binding (very small training data). The approach is very flexible and can be used to train any neural architecture including state-of-the-art models, and shows in most cases strong predictive performance improvements compared to standard supervised learning. Moreover, small models trained by SSL showed similar or better performance than large language model DNABERT2.</p>","PeriodicalId":9209,"journal":{"name":"Briefings in bioinformatics","volume":"25 6","pages":""},"PeriodicalIF":6.8,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531863/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567295","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":"Graph domain adaptation-based framework for gene expression enhancement and cell type identification in large-scale spatially resolved transcriptomics.","authors":"Rongbo Shen, Meiling Cheng, Wencang Wang, Qi Fan, Huan Yan, Jiayue Wen, Zhiyuan Yuan, Jianhua Yao, Yixue Li, Jiao Yuan","doi":"10.1093/bib/bbae576","DOIUrl":"10.1093/bib/bbae576","url":null,"abstract":"<p><p>Spatially resolved transcriptomics (SRT) technologies facilitate gene expression profiling with spatial resolution in a naïve state. Nevertheless, current SRT technologies exhibit limitations, manifesting as either low transcript detection sensitivity or restricted gene throughput. These constraints result in diminished precision and coverage in gene measurement. In response, we introduce SpaGDA, a sophisticated deep learning-based graph domain adaptation framework for both scenarios of gene expression imputation and cell type identification in spatially resolved transcriptomics data by impartially transferring knowledge from reference scRNA-seq data. Systematic benchmarking analyses across several SRT datasets generated from different technologies have demonstrated SpaGDA's superior effectiveness compared to state-of-the-art methods in both scenarios. Further applied to three SRT datasets of different biological contexts, SpaGDA not only better recovers the well-established knowledge sourced from public atlases and existing scientific literature but also yields a more informative spatial expression pattern of genes. Together, these results demonstrate that SpaGDA can be used to overcome the challenges of current SRT data and provide more accurate insights into biological processes or disease development. The SpaGDA is available in https://github.com/shenrb/SpaGDA.</p>","PeriodicalId":9209,"journal":{"name":"Briefings in bioinformatics","volume":"25 6","pages":""},"PeriodicalIF":6.8,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11541786/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603259","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":"CMTT-JTracker: a fully test-time adaptive framework serving automated cell lineage construction.","authors":"Liuyin Chen, Sanyuan Fu, Zijun Zhang","doi":"10.1093/bib/bbae591","DOIUrl":"10.1093/bib/bbae591","url":null,"abstract":"<p><p>Cell tracking is an essential function needed in automated cellular activity monitoring. In practice, processing methods striking a balance between computational efficiency and accuracy as well as demonstrating robust generalizability across diverse cell datasets are highly desired. This paper develops a central-metric fully test-time adaptive framework for cell tracking (CMTT-JTracker). Firstly, a CMTT mechanism is designed for the pre-segmentation of cell images, which enables extracting target information at different resolutions without additional training. Next, a multi-task learning network with the spatial attention scheme is developed to simultaneously realize detection and re-identification tasks based on features extracted by CMTT. Experimental results demonstrate that the CMTT-JTracker exhibits remarkable biological and tracking performance compared with benchmarking tracking methods. It achieves a multiple object tracking accuracy (MOTA) of $0.894$ on Fluo-N2DH-SIM+ and a MOTA of $0.850$ on PhC-C2DL-PSC. Experimental results further confirm that the CMTT applied solely as a segmentation unit outperforms the SOTA segmentation benchmarks on various datasets, particularly excelling in scenarios with dense cells. The Dice coefficients of the CMTT range from a high of $0.928$ to a low of $0.758$ across different datasets.</p>","PeriodicalId":9209,"journal":{"name":"Briefings in bioinformatics","volume":"25 6","pages":""},"PeriodicalIF":6.8,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11570544/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647081","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":"Digital annealing optimization for natural product structure elucidation.","authors":"Chien Lee, Pei-Hua Wang, Yufeng Jane Tseng","doi":"10.1093/bib/bbae600","DOIUrl":"10.1093/bib/bbae600","url":null,"abstract":"<p><p>The digital annealer (DA) leverages its computational capabilities of up to 100 000 bits to address the complex nondeterministic polynomial-time (NP)-complete challenge inherent in elucidating complex structures of natural products. Conventional computational methods often face limitations with complex mixtures, as they struggle to manage the high dimensionality and intertwined relationships typical in natural products, resulting in inefficiencies and inaccuracies. This study reformulates the challenge into a Quadratic Unconstrained Binary Optimization framework, thereby harnessing the quantum-inspired computing power of the DA. Utilizing mass spectrometry data from three distinct herb species and various potential scaffolds, the DA proficiently locates optimal sidechain combinations that adhere to predefined target molecular weights. This methodology enhances the probability of selecting appropriate sidechains and substituted positions and ensures the generation of solutions within a reasonable 5-min window. The findings underscore the transformative potential of the DA in the realms of analytical chemistry and drug discovery, markedly improving both the precision and practicality of natural product structure elucidation.</p>","PeriodicalId":9209,"journal":{"name":"Briefings in bioinformatics","volume":"25 6","pages":""},"PeriodicalIF":6.8,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11570542/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647084","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":"An initial game-theoretic assessment of enhanced tissue preparation and imaging protocols for improved deep learning inference of spatial transcriptomics from tissue morphology.","authors":"Michael Y Fatemi, Yunrui Lu, Alos B Diallo, Gokul Srinivasan, Zarif L Azher, Brock C Christensen, Lucas A Salas, Gregory J Tsongalis, Scott M Palisoul, Laurent Perreard, Fred W Kolling, Louis J Vaickus, Joshua J Levy","doi":"10.1093/bib/bbae476","DOIUrl":"10.1093/bib/bbae476","url":null,"abstract":"<p><p>The application of deep learning to spatial transcriptomics (ST) can reveal relationships between gene expression and tissue architecture. Prior work has demonstrated that inferring gene expression from tissue histomorphology can discern these spatial molecular markers to enable population scale studies, reducing the fiscal barriers associated with large-scale spatial profiling. However, while most improvements in algorithmic performance have focused on improving model architectures, little is known about how the quality of tissue preparation and imaging can affect deep learning model training for spatial inference from morphology and its potential for widespread clinical adoption. Prior studies for ST inference from histology typically utilize manually stained frozen sections with imaging on non-clinical grade scanners. Training such models on ST cohorts is also costly. We hypothesize that adopting tissue processing and imaging practices that mirror standards for clinical implementation (permanent sections, automated tissue staining, and clinical grade scanning) can significantly improve model performance. An enhanced specimen processing and imaging protocol was developed for deep learning-based ST inference from morphology. This protocol featured the Visium CytAssist assay to permit automated hematoxylin and eosin staining (e.g. Leica Bond), 40×-resolution imaging, and joining of multiple patients' tissue sections per capture area prior to ST profiling. Using a cohort of 13 pathologic T Stage-III stage colorectal cancer patients, we compared the performance of models trained on slide prepared using enhanced versus traditional (i.e. manual staining and low-resolution imaging) protocols. Leveraging Inceptionv3 neural networks, we predicted gene expression across serial, histologically-matched tissue sections using whole slide images (WSI) from both protocols. The data Shapley was used to quantify and compare marginal performance gains on a patient-by-patient basis attributed to using the enhanced protocol versus the actual costs of spatial profiling. Findings indicate that training and validating on WSI acquired through the enhanced protocol as opposed to the traditional method resulted in improved performance at lower fiscal cost. In the realm of ST, the enhancement of deep learning architectures frequently captures the spotlight; however, the significance of specimen processing and imaging is often understated. This research, informed through a game-theoretic lens, underscores the substantial impact that specimen preparation/imaging can have on spatial transcriptomic inference from morphology. It is essential to integrate such optimized processing protocols to facilitate the identification of prognostic markers at a larger scale.</p>","PeriodicalId":9209,"journal":{"name":"Briefings in bioinformatics","volume":"25 6","pages":""},"PeriodicalIF":6.8,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11452536/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375186","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":"Current computational tools for protein lysine acylation site prediction.","authors":"Zhaohui Qin, Haoran Ren, Pei Zhao, Kaiyuan Wang, Huixia Liu, Chunbo Miao, Yanxiu Du, Junzhou Li, Liuji Wu, Zhen Chen","doi":"10.1093/bib/bbae469","DOIUrl":"10.1093/bib/bbae469","url":null,"abstract":"<p><p>As a main subtype of post-translational modification (PTM), protein lysine acylations (PLAs) play crucial roles in regulating diverse functions of proteins. With recent advancements in proteomics technology, the identification of PTM is becoming a data-rich field. A large amount of experimentally verified data is urgently required to be translated into valuable biological insights. With computational approaches, PLA can be accurately detected across the whole proteome, even for organisms with small-scale datasets. Herein, a comprehensive summary of 166 in silico PLA prediction methods is presented, including a single type of PLA site and multiple types of PLA sites. This recapitulation covers important aspects that are critical for the development of a robust predictor, including data collection and preparation, sample selection, feature representation, classification algorithm design, model evaluation, and method availability. Notably, we discuss the application of protein language models and transfer learning to solve the small-sample learning issue. We also highlight the prediction methods developed for functionally relevant PLA sites and species/substrate/cell-type-specific PLA sites. In conclusion, this systematic review could potentially facilitate the development of novel PLA predictors and offer useful insights to researchers from various disciplines.</p>","PeriodicalId":9209,"journal":{"name":"Briefings in bioinformatics","volume":"25 6","pages":""},"PeriodicalIF":6.8,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11421846/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142341939","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":"Multi-Cover Persistence (MCP)-based machine learning for polymer property prediction.","authors":"Yipeng Zhang, Cong Shen, Kelin Xia","doi":"10.1093/bib/bbae465","DOIUrl":"https://doi.org/10.1093/bib/bbae465","url":null,"abstract":"<p><p>Accurate and efficient prediction of polymers properties is crucial for polymer design. Recently, data-driven artificial intelligence (AI) models have demonstrated great promise in polymers property analysis. Even with the great progresses, a pivotal challenge in all the AI-driven models remains to be the effective representation of molecules. Here we introduce Multi-Cover Persistence (MCP)-based molecular representation and featurization for the first time. Our MCP-based polymer descriptors are combined with machine learning models, in particular, Gradient Boosting Tree (GBT) models, for polymers property prediction. Different from all previous molecular representation, polymer molecular structure and interactions are represented as MCP, which utilizes Delaunay slices at different dimensions and Rhomboid tiling to characterize the complicated geometric and topological information within the data. Statistic features from the generated persistent barcodes are used as polymer descriptors, and further combined with GBT model. Our model has been extensively validated on polymer benchmark datasets. It has been found that our models can outperform traditional fingerprint-based models and has similar accuracy with geometric deep learning models. In particular, our model tends to be more effective on large-sized monomer structures, demonstrating the great potential of MCP in characterizing more complicated polymer data. This work underscores the potential of MCP in polymer informatics, presenting a novel perspective on molecular representation and its application in polymer science.</p>","PeriodicalId":9209,"journal":{"name":"Briefings in bioinformatics","volume":"25 6","pages":""},"PeriodicalIF":6.8,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11424509/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142341948","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":"NASTRA: accurate analysis of short tandem repeat markers by nanopore sequencing with repeat-structure-aware algorithm.","authors":"Zilin Ren, Jiarong Zhang, Yixiang Zhang, Tingting Yang, Pingping Sun, Jiguo Xue, Xiaochen Bo, Bo Zhou, Jiangwei Yan, Ming Ni","doi":"10.1093/bib/bbae472","DOIUrl":"https://doi.org/10.1093/bib/bbae472","url":null,"abstract":"<p><p>Short-tandem repeats (STRs) are the type of genetic markers extensively utilized in biomedical and forensic applications. Due to sequencing noise in nanopore sequencing, accurate analysis methods are lacking. We developed NASTRA, an innovative tool for Nanopore Autosomal Short Tandem Repeat Analysis, which overcomes traditional database-based methods' limitations and provides a precise germline analysis of STR genetic markers without the need for allele sequence reference. Demonstrating high accuracy in cell line authentication testing and paternity testing, NASTRA significantly surpasses existing methods in both speed and accuracy. This advancement makes it a promising solution for rapid cell line authentication and kinship testing, highlighting the potential of nanopore sequencing for in-field applications.</p>","PeriodicalId":9209,"journal":{"name":"Briefings in bioinformatics","volume":"25 6","pages":""},"PeriodicalIF":6.8,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11424183/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142341949","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":"nsDCC: dual-level contrastive clustering with nonuniform sampling for scRNA-seq data analysis.","authors":"Linjie Wang, Wei Li, Fanghui Zhou, Kun Yu, Chaolu Feng, Dazhe Zhao","doi":"10.1093/bib/bbae477","DOIUrl":"https://doi.org/10.1093/bib/bbae477","url":null,"abstract":"<p><p>Dimensionality reduction and clustering are crucial tasks in single-cell RNA sequencing (scRNA-seq) data analysis, treated independently in the current process, hindering their mutual benefits. The latest methods jointly optimize these tasks through deep clustering. However, contrastive learning, with powerful representation capability, can bridge the gap that common deep clustering methods face, which requires pre-defined cluster centers. Therefore, a dual-level contrastive clustering method with nonuniform sampling (nsDCC) is proposed for scRNA-seq data analysis. Dual-level contrastive clustering, which combines instance-level contrast and cluster-level contrast, jointly optimizes dimensionality reduction and clustering. Multi-positive contrastive learning and unit matrix constraint are introduced in instance- and cluster-level contrast, respectively. Furthermore, the attention mechanism is introduced to capture inter-cellular information, which is beneficial for clustering. The nsDCC focuses on important samples at category boundaries and in minority categories by the proposed nearest boundary sparsest density weight assignment algorithm, making it capable of capturing comprehensive characteristics against imbalanced datasets. Experimental results show that nsDCC outperforms the six other state-of-the-art methods on both real and simulated scRNA-seq data, validating its performance on dimensionality reduction and clustering of scRNA-seq data, especially for imbalanced data. Simulation experiments demonstrate that nsDCC is insensitive to \"dropout events\" in scRNA-seq. Finally, cluster differential expressed gene analysis confirms the meaningfulness of results from nsDCC. In summary, nsDCC is a new way of analyzing and understanding scRNA-seq data.</p>","PeriodicalId":9209,"journal":{"name":"Briefings in bioinformatics","volume":"25 6","pages":""},"PeriodicalIF":6.8,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11427072/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142341950","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}