Frontiers in bioinformatics最新文献

{"title":"A hybrid approach for predicting transcription factors.","authors":"Sumeet Patiyal, Palak Tiwari, Mohit Ghai, Aman Dhapola, Anjali Dhall, Gajendra P S Raghava","doi":"10.3389/fbinf.2024.1425419","DOIUrl":"10.3389/fbinf.2024.1425419","url":null,"abstract":"<p><p>Transcription factors are essential DNA-binding proteins that regulate the transcription rate of several genes and control the expression of genes inside a cell. The prediction of transcription factors with high precision is important for understanding biological processes such as cell differentiation, intracellular signaling, and cell-cycle control. In this study, we developed a hybrid method that combines alignment-based and alignment-free methods for predicting transcription factors with higher accuracy. All models have been trained, tested, and evaluated on a large dataset that contains 19,406 transcription factors and 523,560 non-transcription factor protein sequences. To avoid biases in evaluation, the datasets were divided into training and validation/independent datasets, where 80% of the data was used for training, and the remaining 20% was used for external validation. In the case of alignment-free methods, models were developed using machine learning techniques and the composition-based features of a protein. Our best alignment-free model obtained an AUC of 0.97 on an independent dataset. In the case of the alignment-based method, we used BLAST at different cut-offs to predict the transcription factors. Although the alignment-based method demonstrated excellent performance, it was unable to cover all transcription factors due to instances of no hits. To combine the strengths of both methods, we developed a hybrid method that combines alignment-free and alignment-based methods. In the hybrid method, we added the scores of the alignment-free and alignment-based methods and achieved a maximum AUC of 0.99 on the independent dataset. The method proposed in this study performs better than existing methods. We incorporated the best models in the webserver/Python Package Index/standalone package of \"TransFacPred\" (https://webs.iiitd.edu.in/raghava/transfacpred).</p>","PeriodicalId":73066,"journal":{"name":"Frontiers in bioinformatics","volume":"4 ","pages":"1425419"},"PeriodicalIF":2.8,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11306938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141908534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AUTO-TUNE: selecting the distance threshold for inferring HIV transmission clusters.","authors":"Steven Weaver, Vanessa M Dávila Conn, Daniel Ji, Hannah Verdonk, Santiago Ávila-Ríos, Andrew J Leigh Brown, Joel O Wertheim, Sergei L Kosakovsky Pond","doi":"10.3389/fbinf.2024.1400003","DOIUrl":"10.3389/fbinf.2024.1400003","url":null,"abstract":"<p><p>Molecular surveillance of viral pathogens and inference of transmission networks from genomic data play an increasingly important role in public health efforts, especially for HIV-1. For many methods, the genetic distance threshold used to connect sequences in the transmission network is a key parameter informing the properties of inferred networks. Using a distance threshold that is too high can result in a network with many spurious links, making it difficult to interpret. Conversely, a distance threshold that is too low can result in a network with too few links, which may not capture key insights into clusters of public health concern. Published research using the HIV-TRACE software package frequently uses the default threshold of 0.015 substitutions/site for HIV pol gene sequences, but in many cases, investigators heuristically select other threshold parameters to better capture the underlying dynamics of the epidemic they are studying. Here, we present a general heuristic scoring approach for tuning a distance threshold adaptively, which seeks to prevent the formation of giant clusters. We prioritize the ratio of the sizes of the largest and the second largest cluster, maximizing the number of clusters present in the network. We apply our scoring heuristic to outbreaks with different characteristics, such as regional or temporal variability, and demonstrate the utility of using the scoring mechanism's suggested distance threshold to identify clusters exhibiting risk factors that would have otherwise been more difficult to identify. For example, while we found that a 0.015 substitutions/site distance threshold is typical for US-like epidemics, recent outbreaks like the CRF07_BC subtype among men who have sex with men (MSM) in China have been found to have a lower optimal threshold of 0.005 to better capture the transition from injected drug use (IDU) to MSM as the primary risk factor. Alternatively, in communities surrounding Lake Victoria in Uganda, where there has been sustained heterosexual transmission for many years, we found that a larger distance threshold is necessary to capture a more risk factor-diverse population with sparse sampling over a longer period of time. Such identification may allow for more informed intervention action by respective public health officials.</p>","PeriodicalId":73066,"journal":{"name":"Frontiers in bioinformatics","volume":"4 ","pages":"1400003"},"PeriodicalIF":2.8,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11289888/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141861844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A systematic overview of single-cell transcriptomics databases, their use cases, and limitations.","authors":"Mahnoor N Gondal, Saad Ur Rehman Shah, Arul M Chinnaiyan, Marcin Cieslik","doi":"10.3389/fbinf.2024.1417428","DOIUrl":"10.3389/fbinf.2024.1417428","url":null,"abstract":"<p><p>Rapid advancements in high-throughput single-cell RNA-seq (scRNA-seq) technologies and experimental protocols have led to the generation of vast amounts of transcriptomic data that populates several online databases and repositories. Here, we systematically examined large-scale scRNA-seq databases, categorizing them based on their scope and purpose such as general, tissue-specific databases, disease-specific databases, cancer-focused databases, and cell type-focused databases. Next, we discuss the technical and methodological challenges associated with curating large-scale scRNA-seq databases, along with current computational solutions. We argue that understanding scRNA-seq databases, including their limitations and assumptions, is crucial for effectively utilizing this data to make robust discoveries and identify novel biological insights. Such platforms can help bridge the gap between computational and wet lab scientists through user-friendly web-based interfaces needed for democratizing access to single-cell data. These platforms would facilitate interdisciplinary research, enabling researchers from various disciplines to collaborate effectively. This review underscores the importance of leveraging computational approaches to unravel the complexities of single-cell data and offers a promising direction for future research in the field.</p>","PeriodicalId":73066,"journal":{"name":"Frontiers in bioinformatics","volume":"4 ","pages":"1417428"},"PeriodicalIF":2.8,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11260681/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141749912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA structural features and variability of complete MHC locus sequences.","authors":"Trudy M Wassenaar, Terry Harville, Jonathan Chastain, Visanu Wanchai, David W Ussery","doi":"10.3389/fbinf.2024.1392613","DOIUrl":"10.3389/fbinf.2024.1392613","url":null,"abstract":"<p><p>The major histocompatibility (MHC) locus, also known as the Human Leukocyte Antigen (HLA) genes, is located on the short arm of chromosome 6, and contains three regions (Class I, Class II and Class III). This 5 Mbp locus is one of the most variable regions of the human genome, yet it also encodes a set of highly conserved and important proteins related to immunological response. Genetic variations in this region are responsible for more diseases than in the entire rest of the human genome. However, information on local structural features of the DNA is largely ignored. With recent advances in long-read sequencing technology, it is now becoming possible to sequence the entire 5 Mbp MHC locus, producing complete diploid haplotypes of the whole region. Here, we describe structural maps based on the complete sequences from six different homozygous HLA cell lines. We find long-range structural variability in the different sequences for DNA stacking energy, position preference and curvature, variation in repeats, as well as more local changes in regions forming open chromatin structures, likely to influence gene expression levels. These structural maps can be useful in visualizing large scale structural variation across HLA types, in particular when this can be complemented with epigenetic signals.</p>","PeriodicalId":73066,"journal":{"name":"Frontiers in bioinformatics","volume":"4 ","pages":"1392613"},"PeriodicalIF":2.8,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11251971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141636053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maximum-scoring path sets on pangenome graphs of constant treewidth.","authors":"Broňa Brejová, Travis Gagie, Eva Herencsárová, Tomáš Vinař","doi":"10.3389/fbinf.2024.1391086","DOIUrl":"10.3389/fbinf.2024.1391086","url":null,"abstract":"<p><p>We generalize a problem of finding maximum-scoring segment sets, previously studied by Csűrös (IEEE/ACM Transactions on Computational Biology and Bioinformatics, 2004, 1, 139-150), from sequences to graphs. Namely, given a vertex-weighted graph <i>G</i> and a non-negative startup penalty <i>c</i>, we can find a set of vertex-disjoint paths in <i>G</i> with maximum total score when each path's score is its vertices' total weight minus <i>c</i>. We call this new problem <i>maximum-scoring path sets</i> (MSPS). We present an algorithm that has a linear-time complexity for graphs with a constant treewidth. Generalization from sequences to graphs allows the algorithm to be used on pangenome graphs representing several related genomes and can be seen as a common abstraction for several biological problems on pangenomes, including searching for CpG islands, ChIP-seq data analysis, analysis of region enrichment for functional elements, or simple chaining problems.</p>","PeriodicalId":73066,"journal":{"name":"Frontiers in bioinformatics","volume":"4 ","pages":"1391086"},"PeriodicalIF":2.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11246863/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141621903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The evolution of mammalian Rem2: unraveling the impact of purifying selection and coevolution on protein function, and implications for human disorders.","authors":"Alexander G Lucaci, William E Brew, Jason Lamanna, Avery Selberg, Vincenzo Carnevale, Anna R Moore, Sergei L Kosakovsky Pond","doi":"10.3389/fbinf.2024.1381540","DOIUrl":"10.3389/fbinf.2024.1381540","url":null,"abstract":"<p><p>Rad And Gem-Like GTP-Binding Protein 2 (Rem2), a member of the RGK family of Ras-like GTPases, is implicated in Huntington's disease and Long QT Syndrome and is highly expressed in the brain and endocrine cells. We examine the evolutionary history of Rem2 identified in various mammalian species, focusing on the role of purifying selection and coevolution in shaping its sequence and protein structural constraints. Our analysis of Rem2 sequences across 175 mammalian species found evidence for strong purifying selection in 70% of non-invariant codon sites which is characteristic of essential proteins that play critical roles in biological processes and is consistent with Rem2's role in the regulation of neuronal development and function. We inferred epistatic effects in 50 pairs of codon sites in Rem2, some of which are predicted to have deleterious effects on human health. Additionally, we reconstructed the ancestral evolutionary history of mammalian Rem2 using protein structure prediction of extinct and extant sequences which revealed the dynamics of how substitutions that change the gene sequence of Rem2 can impact protein structure in variable regions while maintaining core functional mechanisms. By understanding the selective pressures, protein- and gene - interactions that have shaped the sequence and structure of the Rem2 protein, we gain a stronger understanding of its biological and functional constraints.</p>","PeriodicalId":73066,"journal":{"name":"Frontiers in bioinformatics","volume":"4 ","pages":"1381540"},"PeriodicalIF":2.8,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11228553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141560465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioinformatics proficiency among African students.","authors":"Ashraf Akintayo Akintola, Abdullahi Tunde Aborode, Muhammed Taofiq Hamza, Augustine Amakiri, Benjamin Moore, Suliat Abdulai, Oluyinka Ajibola Iyiola, Lateef Adegboyega Sulaimon, Effiong Effiong, Adedeji Ogunyemi, Boluwatife Dosunmu, Abdulkadir Yusif Maigoro, Opeyemi Lawal, Kayode Raheem, Ui Wook Hwang","doi":"10.3389/fbinf.2024.1328714","DOIUrl":"10.3389/fbinf.2024.1328714","url":null,"abstract":"<p><p>Bioinformatics, the interdisciplinary field that combines biology, computer science, and data analysis, plays a pivotal role in advancing our understanding of life sciences. In the African context, where the diversity of biological resources and healthcare challenges is substantial, fostering bioinformatics literacy and proficiency among students is important. This perspective provides an overview of the state of bioinformatics literacy among African students, highlighting the significance, challenges, and potential solutions in addressing this critical educational gap. It proposes various strategies to enhance bioinformatics literacy among African students. These include expanding educational resources, fostering collaboration between institutions, and engaging students in research projects. By addressing the current challenges and implementing comprehensive strategies, African students can harness the power of bioinformatics to contribute to innovative solutions in healthcare, agriculture, and biodiversity conservation, ultimately advancing the continent's scientific capabilities and improving the quality of life for her people. In conclusion, promoting bioinformatics literacy among African students is imperative for the continent's scientific development and advancing frontiers of biological research.</p>","PeriodicalId":73066,"journal":{"name":"Frontiers in bioinformatics","volume":"4 ","pages":"1328714"},"PeriodicalIF":2.8,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11222312/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141536364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A comprehensive multi-omics analysis reveals unique signatures to predict Alzheimer's disease.","authors":"Michael Vacher, Rodrigo Canovas, Simon M Laws, James D Doecke","doi":"10.3389/fbinf.2024.1390607","DOIUrl":"10.3389/fbinf.2024.1390607","url":null,"abstract":"<p><strong>Background: </strong>Complex disorders, such as Alzheimer's disease (AD), result from the combined influence of multiple biological and environmental factors. The integration of high-throughput data from multiple omics platforms can provide system overviews, improving our understanding of complex biological processes underlying human disease. In this study, integrated data from four omics platforms were used to characterise biological signatures of AD.</p><p><strong>Method: </strong>The study cohort consists of 455 participants (Control:148, Cases:307) from the Religious Orders Study and Memory and Aging Project (ROSMAP). Genotype (SNP), methylation (CpG), RNA and proteomics data were collected, quality-controlled and pre-processed (SNP = 130; CpG = 83; RNA = 91; Proteomics = 119). Using a diagnosis of Mild Cognitive Impairment (MCI)/AD combined as the target phenotype, we first used Partial Least Squares Regression as an unsupervised classification framework to assess the prediction capabilities for each omics dataset individually. We then used a variation of the sparse generalized canonical correlation analysis (sGCCA) to assess predictions of the combined datasets and identify multi-omics signatures characterising each group of participants.</p><p><strong>Results: </strong>Analysing datasets individually we found methylation data provided the best predictions with an accuracy of 0.63 (95%CI = [0.54-0.71]), followed by RNA, 0.61 (95%CI = [0.52-0.69]), SNP, 0.59 (95%CI = [0.51-0.68]) and proteomics, 0.58 (95%CI = [0.51-0.67]). After integration of the four datasets, predictions were dramatically improved with a resulting accuracy of 0.95 (95% CI = [0.89-0.98]).</p><p><strong>Conclusion: </strong>The integration of data from multiple platforms is a powerful approach to explore biological systems and better characterise the biological signatures of AD. The results suggest that integrative methods can identify biomarker panels with improved predictive performance compared to individual platforms alone. Further validation in independent cohorts is required to validate and refine the results presented in this study.</p>","PeriodicalId":73066,"journal":{"name":"Frontiers in bioinformatics","volume":"4 ","pages":"1390607"},"PeriodicalIF":2.8,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11219798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141499827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human cytokine and coronavirus nucleocapsid protein interactivity using large-scale virtual screens.","authors":"Phillip J Tomezsko, Colby T Ford, Avery E Meyer, Adam M Michaleas, Rafael Jaimes","doi":"10.3389/fbinf.2024.1397968","DOIUrl":"10.3389/fbinf.2024.1397968","url":null,"abstract":"<p><p>Understanding the interactions between SARS-CoV-2 and the human immune system is paramount to the characterization of novel variants as the virus co-evolves with the human host. In this study, we employed state-of-the-art molecular docking tools to conduct large-scale virtual screens, predicting the binding affinities between 64 human cytokines against 17 nucleocapsid proteins from six betacoronaviruses. Our comprehensive <i>in silico</i> analyses reveal specific changes in cytokine-nucleocapsid protein interactions, shedding light on potential modulators of the host immune response during infection. These findings offer valuable insights into the molecular mechanisms underlying viral pathogenesis and may guide the future development of targeted interventions. This manuscript serves as insight into the comparison of deep learning based AlphaFold2-Multimer and the semi-physicochemical based HADDOCK for protein-protein docking. We show the two methods are complementary in their predictive capabilities. We also introduce a novel algorithm for rapidly assessing the binding interface of protein-protein docks using graph edit distance: graph-based interface residue assessment function (GIRAF). The high-performance computational framework presented here will not only aid in accelerating the discovery of effective interventions against emerging viral threats, but extend to other applications of high throughput protein-protein screens.</p>","PeriodicalId":73066,"journal":{"name":"Frontiers in bioinformatics","volume":"4 ","pages":"1397968"},"PeriodicalIF":0.0,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11157076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141297494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BayesAge: A maximum likelihood algorithm to predict epigenetic age.","authors":"Lajoyce Mboning, Liudmilla Rubbi, Michael Thompson, Louis-S Bouchard, Matteo Pellegrini","doi":"10.3389/fbinf.2024.1329144","DOIUrl":"https://doi.org/10.3389/fbinf.2024.1329144","url":null,"abstract":"<p><p><b>Introduction:</b> DNA methylation, specifically the formation of 5-methylcytosine at the C5 position of cytosine, undergoes reproducible changes as organisms age, establishing it as a significant biomarker in aging studies. Epigenetic clocks, which integrate methylation patterns to predict age, often employ linear models based on penalized regression, yet they encounter challenges in handling missing data, count-based bisulfite sequence data, and interpretation. <b>Methods:</b> To address these limitations, we introduce BayesAge, an extension of the scAge methodology originally designed for single-cell DNA methylation analysis. BayesAge employs maximum likelihood estimation (MLE) for age inference, models count data using binomial distributions, and incorporates LOWESS smoothing to capture non-linear methylation-age dynamics. This approach is tailored for bulk bisulfite sequencing datasets. <b>Results:</b> BayesAge demonstrates superior performance compared to scAge. Notably, its age residuals exhibit no age association, offering a less biased representation of epigenetic age variation across populations. Furthermore, BayesAge facilitates the estimation of error bounds on age inference. When applied to down-sampled data, BayesAge achieves a higher coefficient of determination between predicted and actual ages compared to both scAge and penalized regression. <b>Discussion:</b> BayesAge presents a promising advancement in epigenetic age prediction, addressing key challenges encountered by existing models. By integrating robust statistical techniques and tailored methodologies for count-based data, BayesAge offers improved accuracy and interpretability in predicting age from bulk bisulfite sequencing datasets. Its ability to estimate error bounds enhances the reliability of age inference, thereby contributing to a more comprehensive understanding of epigenetic aging processes.</p>","PeriodicalId":73066,"journal":{"name":"Frontiers in bioinformatics","volume":"4 ","pages":"1329144"},"PeriodicalIF":0.0,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11024280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140869053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}