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The Global Landscape of Multiscale Transcriptomic Networks and Key Regulators in Parkinson’s Disease

ABSTRACT: The Global Landscape of Multiscale Transcriptomic Networks and Key Regulators in Parkinson’s Disease

PROVIDER: PRJNA472793 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR7208560_1.fastq.gz	Fastqsanger.gz
	SRR7208560_2.fastq.gz	Fastqsanger.gz
	SRR7208561_1.fastq.gz	Fastqsanger.gz
	SRR7208561_2.fastq.gz	Fastqsanger.gz
	SRR7208562_1.fastq.gz	Fastqsanger.gz

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The Global Landscape of Multiscale Transcriptomic Networks and Key Regulators in Parkinson’s Disease

Project description:Despite the advance of genetic and genomic analysis of Parkinson’s disease (PD), our understanding of PD pathophysiology remains limited due to unclear etiology of idiopathic PD and unavailable integrated approach for large-scale multi-dimensional data. Herein we report a novel multiscale network approach to establish transcriptomic network from postmortem PD brain data. The analysis delineates structures of gene-gene regulatory networks in PD and identifies novel network regulators that are functionally connected to previously identified PD risk genes. We identify STMN2, encoding a neuron-specific stathmin family protein and down-regulated in PD brains, as the top regulator of the transcriptomic network underlying PD. Knock-down of Stmn2 in mice validates its regulatory role, and Stmn2 deficient mice show dopaminergic neuron vulnerability, phosphorylated a-synuclein elevation, and locomotor function deficits. As predicted from the network analysis, reduced STMN2 expression impairs synaptic vesicle trafficking in midbrain neurons. Our approach sheds light on the complexity of PD pathogenic network and thus facilitates identification of novel PD therapeutic targets.

2019-12-03 | GSE114840 | GEO

Multiscale Gene Networks Dissect the Complexity of Breast Cancer

Project description:Despite the enormous amounts of molecular, cellular, and clinical data that are increasingly available for many different types of cancer, it remains a challenge to integrate different dimensions of data to construct mechanistic models that can robustly distinguish key driver genes from passenger genes, predict tumor progression, and tailor therapies optimally for individual patients. We present an integrative biology approach to constructing and analyzing multiscale regulatory networks of breast cancer. We systematically uncover not only known and novel gene subnetworks (modules) linked to breast cancer, but also their key drivers, the majority of which are not transcription factors or signaling molecules. A number of independent lines of evidence support that the predicted key drivers play central roles in breast cancer biology. We predict and experimentally validate ARF1 as a key driver of breast tumor phenotypes, and then demonstrate the ARF1-controlled subnetwork is a novel regulator of intra- and inter- cellular vesicle dynamics involved in epithelial-mesenchymal transition (EMT). We aimed to study the underlying mechanism by which ARF1 has been predicted playing crucial role during carcinogenesis and metastasis. To attest the key function of ARF1 during epithelial mesenchymal transition (EMT), loss of function in vitro study by means of siRNA knockdown of ARF1 in MDA-MB-231 breast cancer cell line was designed. Genome-wide gene expression of nine ARF1 knockdown samples and three control samples were profiled by using the Illumina HumanHT-12 V4.0 expression beadchip platform.

2013-07-18 | E-GEOD-49005 | biostudies-arrayexpress

Multiscale Gene Networks Dissect the Complexity of Breast Cancer

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The landscape of multiscale transcriptomic networks and key regulators in Parkinson's disease.

Project description:Genetic and genomic studies have advanced our knowledge of inherited Parkinson's disease (PD), however, the etiology and pathophysiology of idiopathic PD remain unclear. Herein, we perform a meta-analysis of 8 PD postmortem brain transcriptome studies by employing a multiscale network biology approach to delineate the gene-gene regulatory structures in the substantia nigra and determine key regulators of the PD transcriptomic networks. We identify STMN2, which encodes a stathmin family protein and is down-regulated in PD brains, as a key regulator functionally connected to known PD risk genes. Our network analysis predicts a function of human STMN2 in synaptic trafficking, which is validated in Stmn2-knockdown mouse dopaminergic neurons. Stmn2 reduction in the mouse midbrain causes dopaminergic neuron degeneration, phosphorylated α-synuclein elevation, and locomotor deficits. Our integrative analysis not only begins to elucidate the global landscape of PD transcriptomic networks but also pinpoints potential key regulators of PD pathogenic pathways.

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Defining key transcriptional regulators of extravillous trophoblast differentiation

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Structural cells are key regulators of organ-specific immune response

Project description:Structural cells are key regulators of organ-specific immune response

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Defining key transcriptional regulators of extravillous trophoblast differentiation [RNA-seq]

Project description:Defining key transcriptional regulators of extravillous trophoblast differentiation [RNA-seq]

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