Gene expression analysis method integration and co-expression module detection applied to rare glucide metabolism disorders using ExpHunterSuite

Jabato, Fernando M.; Córdoba-Caballero, José; Rojano, Elena; Romá‐Mateo, Carlos; Sanz, Pascual; Pérez, Belén; Gallego, Diana; Seoane, Pedro; Ranea, Juan A. G.; Perkins, James R.

doi:10.1038/s41598-021-94343-w

Cited by 15 publications

(9 citation statements)

References 54 publications

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“…The genes that are differentially expressed, do not necessarily form interacting modules, and “placing” edges between them only because they are connected in the STRING database is not a valid task. DEGs are not very useful in the first place because dimension reduction still needs to be performed [ 68 ]. There are three main tasks of the analysis conducted here in this study.…”

Section: Discussionmentioning

confidence: 99%

Revealing genetic links of Type 2 diabetes that lead to the development of Alzheimer’s disease

Afzal

Alharbi

Alzarea

et al. 2023

Heliyon

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Section: Discussionmentioning

confidence: 99%

Revealing genetic links of Type 2 diabetes that lead to the development of Alzheimer’s disease

Afzal

Alharbi

Alzarea

et al. 2023

Heliyon

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“…Cells were treated with MG132, bafilomycin or cycloheximide. Whole RNA was extracted from fibroblasts and RNA-Seq was performed by LEXOGEN and analysed with the ExpHunter Suite 70. Expression levels of four selected genes were analysed by qPCR.…”

Section: Discussionmentioning

confidence: 99%

“…Whole RNA was extracted from fibroblasts and RNA-Seq was performed by LEXOGEN and analysed with the ExpHunter Suite. 70 Expression levels of four selected genes were analysed by qPCR. Protein was extracted using RIPA buffer, resolved by SDS-PAGE (sodium dodecyl sulfate-polyacrylamide gel electrophoresis) and immunoblotted following standard biochemical techniques.…”

Section: Discussionmentioning

confidence: 99%

Advancing in Schaaf-Yang syndrome pathophysiology: from bedside to subcellular analyses of truncated MAGEL2

et al. 2022

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BackgroundSchaaf-Yang syndrome (SYS) is caused by truncating mutations in MAGEL2, mapping to the Prader-Willi region (15q11-q13), with an observed phenotype partially overlapping that of Prader-Willi syndrome. MAGEL2 plays a role in retrograde transport and protein recycling regulation. Our aim is to contribute to the characterisation of SYS pathophysiology at clinical, genetic and molecular levels.MethodsWe performed an extensive phenotypic and mutational revision of previously reported patients with SYS. We analysed the secretion levels of amyloid-β 1–40 peptide (Aβ1-40) and performed targeted metabolomic and transcriptomic profiles in fibroblasts of patients with SYS (n=7) compared with controls (n=11). We also transfected cell lines with vectors encoding wild-type (WT) or mutated MAGEL2 to assess stability and subcellular localisation of the truncated protein.ResultsFunctional studies show significantly decreased levels of secreted Aβ1-40 and intracellular glutamine in SYS fibroblasts compared with WT. We also identified 132 differentially expressed genes, including non-coding RNAs (ncRNAs) such as HOTAIR, and many of them related to developmental processes and mitotic mechanisms. The truncated form of MAGEL2 displayed a stability similar to the WT but it was significantly switched to the nucleus, compared with a mainly cytoplasmic distribution of the WT MAGEL2. Based on the updated knowledge, we offer guidelines for the clinical management of patients with SYS.ConclusionA truncated MAGEL2 protein is stable and localises mainly in the nucleus, where it might exert a pathogenic neomorphic effect. Aβ1-40 secretion levels and HOTAIR mRNA levels might be promising biomarkers for SYS. Our findings may improve SYS understanding and clinical management.

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“…Whole RNA was extracted from fibroblasts and RNA-Seq was performed by LEXOGEN, Inc. and analysed with the ExpHunter Suite. [70] Expression levels of four selected genes were analysed by qPCR. Protein was extracted using RIPA buffer, resolved by SDS-PAGE and immunoblotted following standard biochemical techniques.…”

Section: Methodsmentioning

confidence: 99%

Advancing in Schaaf-Yang syndrome pathophysiology: from bedside to subcellular analyses of truncated MAGEL2

Castilla‐Vallmanya

Centeno-Pla

Serrano

et al. 2022

Preprint

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BackgroundSchaaf-Yang syndrome (SYS) is caused by truncating mutations in MAGEL2, mapping to the Prader-Willi region (15q11-q13), with an observed phenotype partially overlapping that of Prader-Willi syndrome. MAGEL2 plays a role in retrograde transport and protein recycling regulation. Our aim is to contribute to the characterization of SYS pathophysiology at clinical, genetic and molecular levels.MethodsWe performed an extensive phenotypic and mutational revision of previously reported SYS patients. We analysed the secretion levels of amyloid-β 1-40 peptide (Aβ1-40), and performed targeted metabolomic and transcriptomic profiles in SYS patients’ fibroblasts (n=7) compared to controls (n=11). We also transfected cell lines with vectors encoding wild-type (WT) or truncated MAGEL2 to assess stability and subcellular localization of the truncated protein.ResultsFunctional studies show significantly decreased levels of secreted Aβ1-40 and intracellular glutamine in SYS fibroblasts compared to wild-type. We also identified 132 differentially expressed genes, including ncRNAs such as HOTAIR, many of them related to developmental processes and mitotic mechanisms. The truncated form of MAGEL2 displayed a stability similar to the wild-type but it was significantly switched to the nucleus, compared to a mainly cytoplasmic distribution of the wild-type MAGEL2. Based on updated knowledge we offer guidelines for clinical management of SYS patients.ConclusionA truncated MAGEL2 protein is stable and localises mainly in the nucleus, where it might exert a pathogenic gain of function effect. Aβ1-40 secretion levels and HOTAIR mRNA levels might be promising biomarkers for SYS. Our findings may improve SYS understanding and clinical management.Key MessagesMAGEL2 truncating mutations cause Schaaf-Yang syndrome (SYS) but the functional effects of the truncated MAGEL2 protein have been poorly defined. By expressing truncated MAGEL2 in cell lines, we now know that a truncated version of the protein is retained in the nucleus, thus exerting a gain-of-function behaviour in addition to the loss of some of its main functions. Patients’ fibroblasts show reduced levels of excreted amyloid beta 1-40 and intracellular glutamine as well as an altered transcriptomic profile, including overexpression of the major regulator HOTAIR. Based on a comprehensive review of genetic and clinical aspects of all reported cases, families and physicians will benefit from the Clinical Management Recommendations that we provide here.

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Gene expression analysis method integration and co-expression module detection applied to rare glucide metabolism disorders using ExpHunterSuite

Cited by 15 publications

References 54 publications

Revealing genetic links of Type 2 diabetes that lead to the development of Alzheimer’s disease

Revealing genetic links of Type 2 diabetes that lead to the development of Alzheimer’s disease

Advancing in Schaaf-Yang syndrome pathophysiology: from bedside to subcellular analyses of truncated MAGEL2

Advancing in Schaaf-Yang syndrome pathophysiology: from bedside to subcellular analyses of truncated MAGEL2

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