Dataset Information

Gene Regulation and Transcriptomics.

ABSTRACT: Borrelia (Borreliella) burgdorferi, along with closely related species, is the etiologic agent of Lyme disease. The spirochete subsists in an enzootic cycle that encompasses acquisition from a vertebrate host to a tick vector and transmission from a tick vector to a vertebrate host. To adapt to its environment and persist in each phase of its enzootic cycle, B. burgdorferi wields three systems to regulate the expression of genes: the RpoN-RpoS alternative sigma factor cascade, the Hk1/Rrp1 two-component system and its product c-di-GMP, and the stringent response mediated by Rel_Bbu and DksA. These regulatory systems respond to enzootic phase-specific signals and are controlled or fine- tuned by transcription factors, including BosR and BadR, as well as small RNAs, including DsrABb and Bb6S RNA. In addition, several other DNA-binding and RNA-binding proteins have been identified, although their functions have not all been defined. Global changes in gene expression revealed by high-throughput transcriptomic studies have elucidated various regulons, albeit technical obstacles have mostly limited this experimental approach to cultivated spirochetes. Regardless, we know that the spirochete, which carries a relatively small genome, regulates the expression of a considerable number of genes required for the transitions between the tick vector and the vertebrate host as well as the adaptation to each.

SUBMITTER: Samuels DS

PROVIDER: S-EPMC7946783 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Gene Regulation and Transcriptomics.

Samuels D Scott DS Lybecker Meghan C MC Yang X Frank XF Ouyang Zhiming Z Bourret Travis J TJ Boyle William K WK Stevenson Brian B Drecktrah Dan D Caimano Melissa J MJ

Current issues in molecular biology 20201210

Borrelia (Borreliella) burgdorferi, along with closely related species, is the etiologic agent of Lyme disease. The spirochete subsists in an enzootic cycle that encompasses acquisition from a vertebrate host to a tick vector and transmission from a tick vector to a vertebrate host. To adapt to its environment and persist in each phase of its enzootic cycle, B. burgdorferi wields three systems to regulate the expression of genes: the RpoN-RpoS alternative sigma factor ...[more]

PMID: 33300497

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Project description:Recent advances in spatial transcriptomics have enabled simultaneous preservation of high-throughput gene expression profiles and the spatial context, enabling high-resolution exploration of distinct regional characterization in tissue. To effectively understand the underlying biological mechanisms within tissue microenvironments, there is a requisite for methods that can accurately capture external spatial heterogeneity and interpret internal gene regulation from spatial transcriptomics data. However, current methods for region identification often lack the simultaneous characterizing of spatial structure and gene regulation, thereby limiting the ability of spatial dissection and gene interpretation. Here, stDCL is developed, a dual graph contrastive learning method to identify spatial domains and interpret gene regulation in spatial transcriptomics data. stDCL adaptively incorporates gene expression data and spatial information via a graph embedding autoencoder, thereby preserving critical information within the latent embedding representations. In addition, dual graph contrastive learning is proposed to train the model, ensuring that the latent embedding representation closely resembles the actual spatial distribution and exhibits cluster similarity. Benchmarking stDCL against other state-of-the-art clustering methods using complex cortex datasets demonstrates its superior accuracy and effectiveness in identifying spatial domains. Our analysis of the imputation matrices generated by stDCL reveals its capability to reconstruct spatial hierarchical structures and refine differential expression assessment. Furthermore, it is demonstrated that the versatility of stDCL in interpretability of gene regulation, spatial heterogeneity at high resolution, and embryonic developmental patterns. In addition, it is also showed that stDCL can successfully annotate disease-associated astrocyte subtypes in Alzheimer's disease and unravel multiple relevant pathways and regulatory mechanisms.

Dataset Information

Gene Regulation and Transcriptomics.

Publications

Gene Regulation and Transcriptomics.

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