FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4384071772> ?p ?o ?g. }

• W4384071772 abstract "Inter-organ communication is a vital process to maintain physiologic homeostasis, and its dysregulation contributes to many human diseases. Beginning with the discovery of insulin over a century ago, characterization of molecules responsible for signal between tissues has required careful and elegant experimentation where these observations have been integral to deciphering physiology and disease. Given that circulating bioactive factors are stable in serum, occur naturally, and are easily assayed from blood, they present obvious focal molecules for therapeutic intervention and biomarker development. For example, physiologic dissection of the actions of soluble proteins such as proprotein convertase subtilisin/kexin type 9 (PCSK9) and glucagon-like peptide 1 (GLP1) have yielded among the most promising therapeutics to treat cardiovascular disease and obesity, respectively–. A major obstacle in the characterization of such soluble factors is that defining their tissues and pathways of action requires extensive experimental testing in cells and animal models. Recently, studies have shown that secreted proteins mediating inter-tissue signaling could be identified by “brute-force” surveys of all genes within RNA-sequencing measures across tissues within a population–. Expanding on this intuition, we reasoned that parallel strategies could be leveraged to understand how individual genes mediate signaling across metabolic tissues through correlative analysis of genetic variation. Thus, genetics could aid in understanding cross-organ signaling by adopting a genecentric approach. Here, we surveyed gene-gene genetic correlation structure for ∼6.1×10^ gene pairs across 18 metabolic tissues in 310 individuals where variation of genes such as FGF21, ADIPOQ, GCG and IL6 showed enrichments which recapitulate experimental observations.Further, similar analyses were applied to explore both local signaling mechanisms (liver PCSK9) as well as genes encoding enzymes producing metabolites (adipose PNPLA2), where genetic correlation structure aligned with known roles for these critical metabolic pathways. Finally, we utilized this resource to suggest new functions for metabolic coordination between organs. For example, we prioritized key proteins for putative signaling between skeletal muscle and hippocampus, and further suggest colon as a central coordinator for systemic circadian clocks.We refer to this resource as Genetically-Derived Correlations Across Tissues (GD-CAT) where all tools and data are built into a web portal enabling users to perform these analyses without a single line of code (). This resource enables querying of any gene in any tissue to find genetic coregulation of genes, cell types, pathways and network architectures across metabolic organs." @default.
• W4384071772 created "2023-07-13" @default.
• W4384071772 date "2023-07-12" @default.
• W4384071772 modified "2023-09-28" @default.
• W4384071772 title "Reviewer #1 (Public Review): Leveraging genetic correlation structure to target discrete signaling mechanisms across metabolic tissues" @default.
• W4384071772 doi "https://doi.org/10.7554/elife.88863.1.sa1" @default.
• W4384071772 hasPublicationYear "2023" @default.
• W4384071772 type Work @default.
• W4384071772 citedByCount "0" @default.
• W4384071772 crossrefType "peer-review" @default.
• W4384071772 hasBestOaLocation W43840717721 @default.
• W4384071772 hasConcept C104317684 @default.
• W4384071772 hasConcept C126322002 @default.
• W4384071772 hasConcept C134018914 @default.
• W4384071772 hasConcept C2775905019 @default.
• W4384071772 hasConcept C2778163477 @default.
• W4384071772 hasConcept C2778824825 @default.
• W4384071772 hasConcept C2779134260 @default.
• W4384071772 hasConcept C2780072125 @default.
• W4384071772 hasConcept C2780948078 @default.
• W4384071772 hasConcept C2781197716 @default.
• W4384071772 hasConcept C2908647359 @default.
• W4384071772 hasConcept C43554185 @default.
• W4384071772 hasConcept C54355233 @default.
• W4384071772 hasConcept C60644358 @default.
• W4384071772 hasConcept C70721500 @default.
• W4384071772 hasConcept C71924100 @default.
• W4384071772 hasConcept C86803240 @default.
• W4384071772 hasConcept C99454951 @default.
• W4384071772 hasConceptScore W4384071772C104317684 @default.
• W4384071772 hasConceptScore W4384071772C126322002 @default.
• W4384071772 hasConceptScore W4384071772C134018914 @default.
• W4384071772 hasConceptScore W4384071772C2775905019 @default.
• W4384071772 hasConceptScore W4384071772C2778163477 @default.
• W4384071772 hasConceptScore W4384071772C2778824825 @default.
• W4384071772 hasConceptScore W4384071772C2779134260 @default.
• W4384071772 hasConceptScore W4384071772C2780072125 @default.
• W4384071772 hasConceptScore W4384071772C2780948078 @default.
• W4384071772 hasConceptScore W4384071772C2781197716 @default.
• W4384071772 hasConceptScore W4384071772C2908647359 @default.
• W4384071772 hasConceptScore W4384071772C43554185 @default.
• W4384071772 hasConceptScore W4384071772C54355233 @default.
• W4384071772 hasConceptScore W4384071772C60644358 @default.
• W4384071772 hasConceptScore W4384071772C70721500 @default.
• W4384071772 hasConceptScore W4384071772C71924100 @default.
• W4384071772 hasConceptScore W4384071772C86803240 @default.
• W4384071772 hasConceptScore W4384071772C99454951 @default.
• W4384071772 hasLocation W43840717721 @default.
• W4384071772 hasOpenAccess W4384071772 @default.
• W4384071772 hasPrimaryLocation W43840717721 @default.
• W4384071772 hasRelatedWork W1989786519 @default.
• W4384071772 hasRelatedWork W2004683380 @default.
• W4384071772 hasRelatedWork W2098813930 @default.
• W4384071772 hasRelatedWork W2563621953 @default.
• W4384071772 hasRelatedWork W3044232050 @default.
• W4384071772 hasRelatedWork W3088068966 @default.
• W4384071772 hasRelatedWork W3202828330 @default.
• W4384071772 hasRelatedWork W4293769634 @default.
• W4384071772 hasRelatedWork W4360596321 @default.
• W4384071772 hasRelatedWork W621289652 @default.
• W4384071772 isParatext "false" @default.
• W4384071772 isRetracted "false" @default.
• W4384071772 workType "peer-review" @default.