Briefings in bioinformatics最新文献

{"title":"Polygenic prediction for underrepresented populations through transfer learning by utilizing genetic similarity shared with European populations.","authors":"Yiyang Zhu, Wenying Chen, Kexuan Zhu, Yuxin Liu, Shuiping Huang, Ping Zeng","doi":"10.1093/bib/bbaf048","DOIUrl":"10.1093/bib/bbaf048","url":null,"abstract":"<p><p>Because current genome-wide association studies are primarily conducted in individuals of European ancestry and information disparities exist among different populations, the polygenic score derived from Europeans thus exhibits poor transferability. Borrowing the idea of transfer learning, which enables the utilization of knowledge acquired from auxiliary samples to enhance learning capability in target samples, we propose transPGS, a novel polygenic score method, for genetic prediction in underrepresented populations by leveraging genetic similarity shared between the European and non-European populations while explaining the trans-ethnic difference in linkage disequilibrium (LD) and effect sizes. We demonstrate the usefulness and robustness of transPGS in elevated prediction accuracy via individual-level and summary-level simulations and apply it to seven continuous phenotypes and three diseases in the African, Chinese, and East Asian populations of the UK Biobank and Genetic Epidemiology Research Study on Adult Health and Aging cohorts. We further reveal that distinct LD and minor allele frequency patterns across ancestral groups are responsible for the dissatisfactory portability of PGS.</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/PMC11794457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188337","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":"Do protein language models learn phylogeny?","authors":"Sanjana Tule, Gabriel Foley, Mikael Bodén","doi":"10.1093/bib/bbaf047","DOIUrl":"10.1093/bib/bbaf047","url":null,"abstract":"<p><p>Deep machine learning demonstrates a capacity to uncover evolutionary relationships directly from protein sequences, in effect internalising notions inherent to classical phylogenetic tree inference. We connect these two paradigms by assessing the capacity of protein-based language models (pLMs) to discern phylogenetic relationships without being explicitly trained to do so. We evaluate ESM2, ProtTrans, and MSA-Transformer relative to classical phylogenetic methods, while also considering sequence insertions and deletions (indels) across 114 Pfam datasets. The largest ESM2 model tends to outperform other pLMs (including the multimodal ESM3) by recovering phylogenetic relationships among homologous protein sequences in both low- and high-gap settings. pLMs agree with conventional phylogenetic methods in general, but more so for protein families with fewer implied indels, highlighting indels as a key factor differentiating classical phylogenetics from pLMs. We find that pLMs preferentially capture broader as opposed to finer evolutionary relationships within a specific protein family, where ESM2 has a sweet spot for highly divergent sequences, at remote distance. Less than 10% of neurons are sufficient to broadly recapitulate classical phylogenetic distances; when used in isolation, the difference between the paradigms is further diminished. We show these neurons are polysemantic, shared among different homologous families but never fully overlapping. We highlight the potential of ESM2 as a complementary tool for phylogenetic analysis, especially when extending to remote homologs that are difficult to align and imply complex histories of insertions and deletions. Implementations of analyses are available at https://github.com/santule/pLMEvo.</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/PMC11847157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482209","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":"BICEP: Bayesian inference for rare genomic variant causality evaluation in pedigrees.","authors":"Cathal Ormond, Niamh M Ryan, Mathieu Cap, William Byerley, Aiden Corvin, Elizabeth A Heron","doi":"10.1093/bib/bbae624","DOIUrl":"10.1093/bib/bbae624","url":null,"abstract":"<p><p>Next-generation sequencing is widely applied to the investigation of pedigree data for gene discovery. However, identifying plausible disease-causing variants within a robust statistical framework is challenging. Here, we introduce BICEP: a Bayesian inference tool for rare variant causality evaluation in pedigree-based cohorts. BICEP calculates the posterior odds that a genomic variant is causal for a phenotype based on the variant cosegregation as well as a priori evidence such as deleteriousness and functional consequence. BICEP can correctly identify causal variants for phenotypes with both Mendelian and complex genetic architectures, outperforming existing methodologies. Additionally, BICEP can correctly down-weight common variants that are unlikely to be involved in phenotypic liability in the context of a pedigree, even if they have reasonable cosegregation patterns. The output metrics from BICEP allow for the quantitative comparison of variant causality within and across pedigrees, which is not possible with existing approaches.</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/PMC11645550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827358","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":"Exploring the potential of large language model-based chatbots in challenges of ribosome profiling data analysis: a review.","authors":"Zheyu Ding, Rong Wei, Jianing Xia, Yonghao Mu, Jiahuan Wang, Yingying Lin","doi":"10.1093/bib/bbae641","DOIUrl":"10.1093/bib/bbae641","url":null,"abstract":"<p><p>Ribosome profiling (Ribo-seq) provides transcriptome-wide insights into protein synthesis dynamics, yet its analysis poses challenges, particularly for nonbioinformatics researchers. Large language model-based chatbots offer promising solutions by leveraging natural language processing. This review explores their convergence, highlighting opportunities for synergy. We discuss challenges in Ribo-seq analysis and how chatbots mitigate them, facilitating scientific discovery. Through case studies, we illustrate chatbots' potential contributions, including data analysis and result interpretation. Despite the absence of applied examples, existing software underscores the value of chatbots and the large language model. We anticipate their pivotal role in future Ribo-seq analysis, overcoming limitations. Challenges such as model bias and data privacy require attention, but emerging trends offer promise. The integration of large language models and Ribo-seq analysis holds immense potential for advancing translational regulation and gene expression understanding.</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/PMC11638007/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817162","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":"FunlncModel: integrating multi-omic features from upstream and downstream regulatory networks into a machine learning framework to identify functional lncRNAs.","authors":"Yan-Yu Li, Feng-Cui Qian, Guo-Rui Zhang, Xue-Cang Li, Li-Wei Zhou, Zheng-Min Yu, Wei Liu, Qiu-Yu Wang, Chun-Quan Li","doi":"10.1093/bib/bbae623","DOIUrl":"10.1093/bib/bbae623","url":null,"abstract":"<p><p>Accumulating evidence indicates that long noncoding RNAs (lncRNAs) play important roles in molecular and cellular biology. Although many algorithms have been developed to reveal their associations with complex diseases by using downstream targets, the upstream (epi)genetic regulatory information has not been sufficiently leveraged to predict the function of lncRNAs in various biological processes. Therefore, we present FunlncModel, a machine learning-based interpretable computational framework, which aims to screen out functional lncRNAs by integrating a large number of (epi)genetic features and functional genomic features from their upstream/downstream multi-omic regulatory networks. We adopted the random forest method to mine nearly 60 features in three categories from >2000 datasets across 11 data types, including transcription factors (TFs), histone modifications, typical enhancers, super-enhancers, methylation sites, and mRNAs. FunlncModel outperformed alternative methods for classification performance in human embryonic stem cell (hESC) (0.95 Area Under Curve (AUROC) and 0.97 Area Under the Precision-Recall Curve (AUPRC)). It could not only infer the most known lncRNAs that influence the states of stem cells, but also discover novel high-confidence functional lncRNAs. We extensively validated FunlncModel's efficacy by up to 27 cancer-related functional prediction tasks, which involved multiple cancer cell growth processes and cancer hallmarks. Meanwhile, we have also found that (epi)genetic regulatory features, such as TFs and histone modifications, serve as strong predictors for revealing the function of lncRNAs. Overall, FunlncModel is a strong and stable prediction model for identifying functional lncRNAs in specific cellular contexts. FunlncModel is available as a web server at https://bio.liclab.net/FunlncModel/.</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/PMC11601888/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738397","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":"LIMO-GCN: a linear model-integrated graph convolutional network for predicting Alzheimer disease genes.","authors":"Cui-Xiang Lin, Hong-Dong Li, Jianxin Wang","doi":"10.1093/bib/bbae611","DOIUrl":"10.1093/bib/bbae611","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a complex disease with its genetic etiology not fully understood. Gene network-based methods have been proven promising in predicting AD genes. However, existing approaches are limited in their ability to model the nonlinear relationship between networks and disease genes, because (i) any data can be theoretically decomposed into the sum of a linear part and a nonlinear part, (ii) the linear part can be best modeled by a linear model since a nonlinear model is biased and can be easily overfit, and (iii) existing methods do not separate the linear part from the nonlinear part when building the disease gene prediction model. To address the limitation, we propose linear model-integrated graph convolutional network (LIMO-GCN), a generic disease gene prediction method that models the data linearity and nonlinearity by integrating a linear model with GCN. The reason to use GCN is that it is by design naturally suitable to dealing with network data, and the reason to integrate a linear model is that the linearity in the data can be best modeled by a linear model. The weighted sum of the prediction of the two components is used as the final prediction of LIMO-GCN. Then, we apply LIMO-GCN to the prediction of AD genes. LIMO-GCN outperforms the state-of-the-art approaches including GCN, network-wide association studies, and random walk. Furthermore, we show that the top-ranked genes are significantly associated with AD based on molecular evidence from heterogeneous genomic data. Our results indicate that LIMO-GCN provides a novel method for prioritizing AD genes.</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/PMC11596108/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142726293","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":"ONDSA: a testing framework based on Gaussian graphical models for differential and similarity analysis of multiple omics networks.","authors":"Jiachen Chen, Joanne M Murabito, Kathryn L Lunetta","doi":"10.1093/bib/bbae610","DOIUrl":"10.1093/bib/bbae610","url":null,"abstract":"<p><p>The Gaussian graphical model (GGM) is a statistical network approach that represents conditional dependencies among components, enabling a comprehensive exploration of disease mechanisms using high-throughput multi-omics data. Analyzing differential and similar structures in biological networks across multiple clinical conditions can reveal significant biological pathways and interactions associated with disease onset and progression. However, most existing methods for estimating group differences in sparse GGMs only apply to comparisons between two groups, and the challenging problem of multiple testing across multiple GGMs persists. This limitation hinders the ability to uncover complex biological insights that arise from comparing multiple conditions simultaneously. To address these challenges, we propose the Omics Networks Differential and Similarity Analysis (ONDSA) framework, specifically designed for continuous omics data. ONDSA tests for structural differences and similarities across multiple groups, effectively controlling the false discovery rate (FDR) at a desired level. Our approach focuses on entry-wise comparisons of precision matrices across groups, introducing two test statistics to sequentially estimate structural differences and similarities while adjusting for correlated effects in FDR control procedures. We show via comprehensive simulations that ONDSA outperforms existing methods under a range of graph structures and is a valuable tool for joint comparisons of multiple GGMs. We also illustrate our method through the detection of neuroinflammatory pathways in a multi-omics dataset from the Framingham Heart Study Offspring cohort, involving three apolipoprotein E genotype groups. It highlights ONDSA's ability to provide a more holistic view of biological interactions and disease mechanisms through multi-omics data integration.</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/PMC11586129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142709265","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":"Online-adjusted evolutionary biclustering algorithm to identify significant modules in gene expression data.","authors":"Raúl Galindo-Hernández, Katya Rodríguez-Vázquez, Edgardo Galán-Vásquez, Carlos Ignacio Hernández Castellanos","doi":"10.1093/bib/bbae681","DOIUrl":"10.1093/bib/bbae681","url":null,"abstract":"<p><p>Analyzing gene expression data helps the identification of significant biological relationships in genes. With a growing number of open biological datasets available, it is paramount to use reliable and innovative methods to perform in-depth analyses of biological data and ensure that informed decisions are made based on accurate information. Evolutionary algorithms have been successful in the analysis of biological datasets. However, there is still room for improvement, and further analysis should be conducted. In this work, we propose Online-Adjusted EVOlutionary Biclustering algorithm (OAEVOB), a novel evolutionary-based biclustering algorithm that efficiently handles vast gene expression data. OAEVOB incorporates an online-adjustment feature that efficiently identifies significant groups by updating the mutation probability and crossover parameters. We utilize measurements such as Pearson correlation, distance correlation, biweight midcorrelation, and mutual information to assess the similarity of genes in the biclusters. Algorithms in the specialized literature do not address generalization to diverse gene expression sources. Therefore, to evaluate OAEVOB's performance, we analyzed six gene expression datasets obtained from diverse sequencing data sources, specifically Deoxyribonucleic Acid microarray, Ribonucleic Acid (RNA) sequencing, and single-cell RNA sequencing, which are subject to a thorough examination. OAEVOB identified significant broad gene expression biclusters with correlations greater than $0.5$ across all similarity measurements employed. Additionally, when biclusters are evaluated by functional enrichment analysis, they exhibit biological functions, suggesting that OAEVOB effectively identifies biclusters with specific cancer and tissue-related genes in the analyzed datasets. We compared the OAEVOB's performance with state-of-the-art methods and outperformed them showing robustness to noise, overlapping, sequencing data sources, and gene coverage.</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/PMC11695933/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920882","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":"Understanding relationships between epigenetic marks and their application to robust assignment of chromatin states.","authors":"Leandro Murgas, Gianluca Pollastri, Erick Riquelme, Mauricio Sáez, Alberto J M Martin","doi":"10.1093/bib/bbae638","DOIUrl":"10.1093/bib/bbae638","url":null,"abstract":"<p><p>Structural changes of chromatin modulate access to DNA for the molecular machinery involved in the control of transcription. These changes are linked to variations in epigenetic marks that allow to classify chromatin in different functional states depending on the pattern of these histone marks. Importantly, alterations in chromatin states are known to be linked with various diseases, and their changes are known to explain processes such as cellular proliferation. For most of the available samples, there are not enough epigenomic data available to accurately determine chromatin states for the cells affected in each of them. This is mainly due to high costs of performing this type of experiments but also because of lack of a sufficient amount of sample or its degradation. In this work, we describe a cascade method based on a random forest algorithm to infer epigenetic marks, and by doing so, to identify relationships between different histone marks. Importantly, our approach also reduces the number of experimentally determined marks required to assign chromatin states. Moreover, in this work we have identified several relationships between patterns of different histone marks, which strengthens the evidence in favor of a redundant epigenetic code.</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/PMC11631260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806106","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":"CPARI: a novel approach combining cell partitioning with absolute and relative imputation to address dropout in single-cell RNA-seq data.","authors":"Yi Zhang, Yin Wang, Xinyuan Liu, Xi Feng","doi":"10.1093/bib/bbae668","DOIUrl":"10.1093/bib/bbae668","url":null,"abstract":"<p><p>A key challenge in analyzing single-cell RNA sequencing data is the large number of false zeros, known as \"dropout zeros\", which are caused by technical limitations such as shallow sequencing depth or inefficient mRNA capture. To address this challenge, we propose a novel imputation model called CPARI, which combines cell partitioning with our designed absolute and relative imputation methods. Initially, CPARI employs a new approach to select highly variable genes and constructs an average consensus matrix using C-mean fuzzy clustering-based blockchain technology to obtain results at different resolutions. Hierarchical clustering is then applied to further refine these blocks, resulting in well-defined cellular partitions. Subsequently, CPARI identifies dropout events and determines the imputation positions of these identified zeros. An autoencoder is trained within each cellular block to learn gene features and reconstruct data. Our uniquely defined absolute imputation technique is first applied to the identified positions, followed by our relative imputation technique to address remaining dropout zeros, ensuring that both global consistency and local variation are maintained. Through comprehensive analyses conducted on simulated and real scRNA-seq datasets, including quantitative assessment, differential expression analysis, cell clustering, cell trajectory inference, robustness evaluation, and large-scale data imputation, CPARI demonstrates superior performance compared to 12 other art-of-state imputation models. Additionally, ablation experiments further confirm the significance and necessity of both the cell partitioning and relative imputation components of CPARI. Notably, CPARI as a new denoising approach could distinguish between real biological zeros and dropout zeros and minimize false positives, and maximize the accuracy of imputation.</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/PMC11666288/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142880666","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}