340 research outputs found
sj-pdf-1-pul-10.1177_20458940211054325 - Supplemental material for Metabolic endophenotype associated with right ventricular glucose uptake in pulmonary hypertension
No full textSupplemental material, sj-pdf-1-pul-10.1177_20458940211054325 for Metabolic endophenotype associated with right ventricular glucose uptake in pulmonary hypertension by Samar Farha, Suzy Comhair, Yuan Hou, Margaret M. Park, Jacqueline Sharp, Laura Peterson, Belinda Willard, Renliang Zhang, Frank P. DiFilippo, Donald Neumann, W.H. Wilson Tang, Feixiong Cheng and Serpil Erzurum in Pulmonary Circulation</p
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Mapping the gene network landscape of Alzheimer’s disease through integrating genomics and transcriptomics
No full textIntegration of multi-omics data with molecular interaction networks enables elucidation of the pathophysiology of Alzheimer's disease (AD). Using the latest genome-wide association studies (GWAS) including proxy cases and the STRING interactome, we identified an AD network of 142 risk genes and 646 network-proximal genes, many of which were linked to synaptic functions annotated by mouse knockout data. The proximal genes were confirmed to be enriched in a replication GWAS of autopsy-documented cases. By integrating the AD gene network with transcriptomic data of AD and healthy temporal cortices, we identified 17 gene clusters of pathways, such as up-regulated complement activation and lipid metabolism, down-regulated cholinergic activity, and dysregulated RNA metabolism and proteostasis. The relationships among these pathways were further organized by a hierarchy of the AD network pinpointing major parent nodes in graph structure including endocytosis and immune reaction. Control analyses were performed using transcriptomics from cerebellum and a brain-specific interactome. Further integration with cell-specific RNA sequencing data demonstrated genes in our clusters of immunoregulation and complement activation were highly expressed in microglia
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