{"title":"Constructing the dynamic transcriptional regulatory networks to identify phenotype-specific transcription regulators.","authors":"Yang Guo, Zhiqiang Xiao","doi":"10.1093/bib/bbae542","DOIUrl":null,"url":null,"abstract":"<p><p>The transcriptional regulatory network (TRN) is a graph framework that helps understand the complex transcriptional regulation mechanisms in the transcription process. Identifying the phenotype-specific transcription regulators is vital to reveal the functional roles of transcription elements in associating the specific phenotypes. Although many methods have been developed towards detecting the phenotype-specific transcription elements based on the static TRN in the past decade, most of them are not satisfactory for elucidating the phenotype-related functional roles of transcription regulators in multiple levels, as the dynamic characteristics of transcription regulators are usually ignored in static models. In this study, we introduce a novel framework called DTGN to identify the phenotype-specific transcription factors (TFs) and pathways by constructing dynamic TRNs. We first design a graph autoencoder model to integrate the phenotype-oriented time-series gene expression data and static TRN to learn the temporal representations of genes. Then, based on the learned temporal representations of genes, we develop a statistical method to construct a series of dynamic TRNs associated with the development of specific phenotypes. Finally, we identify the phenotype-specific TFs and pathways from the constructed dynamic TRNs. Results from multiple phenotypic datasets show that the proposed DTGN framework outperforms most existing methods in identifying phenotype-specific TFs and pathways. Our framework offers a new approach to exploring the functional roles of transcription regulators that associate with specific phenotypes in a dynamic model.</p>","PeriodicalId":9209,"journal":{"name":"Briefings in bioinformatics","volume":"25 6","pages":""},"PeriodicalIF":6.8000,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11503644/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Briefings in bioinformatics","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1093/bib/bbae542","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
引用次数: 0
Abstract
The transcriptional regulatory network (TRN) is a graph framework that helps understand the complex transcriptional regulation mechanisms in the transcription process. Identifying the phenotype-specific transcription regulators is vital to reveal the functional roles of transcription elements in associating the specific phenotypes. Although many methods have been developed towards detecting the phenotype-specific transcription elements based on the static TRN in the past decade, most of them are not satisfactory for elucidating the phenotype-related functional roles of transcription regulators in multiple levels, as the dynamic characteristics of transcription regulators are usually ignored in static models. In this study, we introduce a novel framework called DTGN to identify the phenotype-specific transcription factors (TFs) and pathways by constructing dynamic TRNs. We first design a graph autoencoder model to integrate the phenotype-oriented time-series gene expression data and static TRN to learn the temporal representations of genes. Then, based on the learned temporal representations of genes, we develop a statistical method to construct a series of dynamic TRNs associated with the development of specific phenotypes. Finally, we identify the phenotype-specific TFs and pathways from the constructed dynamic TRNs. Results from multiple phenotypic datasets show that the proposed DTGN framework outperforms most existing methods in identifying phenotype-specific TFs and pathways. Our framework offers a new approach to exploring the functional roles of transcription regulators that associate with specific phenotypes in a dynamic model.
期刊介绍:
Briefings in Bioinformatics is an international journal serving as a platform for researchers and educators in the life sciences. It also appeals to mathematicians, statisticians, and computer scientists applying their expertise to biological challenges. The journal focuses on reviews tailored for users of databases and analytical tools in contemporary genetics, molecular and systems biology. It stands out by offering practical assistance and guidance to non-specialists in computerized methodologies. Covering a wide range from introductory concepts to specific protocols and analyses, the papers address bacterial, plant, fungal, animal, and human data.
The journal's detailed subject areas include genetic studies of phenotypes and genotypes, mapping, DNA sequencing, expression profiling, gene expression studies, microarrays, alignment methods, protein profiles and HMMs, lipids, metabolic and signaling pathways, structure determination and function prediction, phylogenetic studies, and education and training.