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Systems biology approaches to unravel the molecular and genetic architecture of Alzheimer's disease and related tauopathies.

ABSTRACT: Over the years, genetic studies have identified multiple genetic risk variants associated with neurodegenerative disorders and helped reveal new biological pathways and genes of interest. However, genetic risk variants commonly reside in non-coding regions and may regulate distant genes rather than the nearest gene, as well as a gene's interaction partners in biological networks. Systems biology and functional genomics approaches provide the framework to unravel the functional significance of genetic risk variants in disease. In this review, we summarize the genetic and transcriptomic studies of Alzheimer's disease and related tauopathies and focus on the advantages of performing systems-level analyses to interrogate the biological pathways underlying neurodegeneration. Finally, we highlight new avenues of multi-omics analysis with single-cell approaches, which provide unparalleled opportunities to systematically explore cellular heterogeneity, and present an example of how to integrate publicly available single-cell datasets. Systems-level analysis has illuminated the function of many disease risk genes, but much work remains to study tauopathies and to understand spatiotemporal gene expression changes of specific cell types.

SUBMITTER: Miyoshi E

PROVIDER: S-EPMC8616667 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Systems biology approaches to unravel the molecular and genetic architecture of Alzheimer's disease and related tauopathies.

Miyoshi Emily E Morabito Samuel S Swarup Vivek V

Neurobiology of disease 20211009

Over the years, genetic studies have identified multiple genetic risk variants associated with neurodegenerative disorders and helped reveal new biological pathways and genes of interest. However, genetic risk variants commonly reside in non-coding regions and may regulate distant genes rather than the nearest gene, as well as a gene's interaction partners in biological networks. Systems biology and functional genomics approaches provide the framework to unravel the functional significance of ge ...[more]

PMID: 34634459

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Project description:Background: Clostridium thermocellum is a Gram-positive, anaerobic, thermophilic bacterium with a great potential to be a consolidated bioprocessing biocatalyst that can ferment cellulose to ethanol. To understand its physiology and genetic targets for future strain development, we have carried out several studies including ethanol-tolerant mutant resequencing and ethanol shock experiments. Methods: In this study, several approaches were applied to enrich mRNA for next-generation sequencing based RNA-Seq and the transcriptomic profiling of C. thermocellum ethanol shock responses was investigated using high-density tiling array and RNA-Seq. Correlations among different transcriptomic platforms of expression array, tiling array, and RNA-Seq were then compared, and data generated from systems biology studies were used for transcriptional architecture improvement. Results: Our results indicate that cloning-based Sanger sequencing can be used for mRNA enrichment ratio determination, and low-copy number plasmid performed better than high-copy one for cDNA library construction. In addition, high correlations were observed among same array platform using different analyses as well as those between two different array platforms of tiling and expression array when probe intensity was compared. Correlations between RNA-Seq and array results especially the one between RNA-Seq and tiling array are also high. Moreover, combining both RNA-Seq and microarray data the transcriptional architecture of C. thermocellum including the prediction and verification of novel transcript (gene), transcriptional start site (TSS), CAZyme genes, ncRNA, and operon were systematically updated and improved. Conclusions: RNA-seq has high correlation with array-based transcriptomic platforms and can provide additional information for transcriptional architecture and genome annotation improvement, which will facilitate future omics-based studies. A twelve array study using total RNA recovered from wild-type cultures of Clostridium thermocellum at different time points of 30, 60, and 120 min post-inoculation with 3.95 g/L [0.5% (v/v)] treatment compred to that of control without ethanol supplementation. Two biological replicates for treatment and control condition.

Dataset Information

Systems biology approaches to unravel the molecular and genetic architecture of Alzheimer's disease and related tauopathies.

Publications

Systems biology approaches to unravel the molecular and genetic architecture of Alzheimer's disease and related tauopathies.

Similar Datasets

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