scholarly journals Systems-level analysis of transcriptome reorganization during liver regeneration

2021 ◽  
Author(s):  
Manisri Porukala ◽  
P K Vinod
Keyword(s):  
Liver Regeneration ◽  
Rna Sequencing ◽  
Integrated Circuit ◽  
Ribosome Biogenesis ◽  
Network Inference ◽  
Epithelial To Mesenchymal Transition ◽  
Population Level ◽  
Sequencing Data ◽  
Mesenchymal Transition ◽  
Reversible Transitions

Tissue homeostasis and regeneration depend on the reversible transitions between quiescence (G0) and proliferation. The liver has a remarkable capacity to regenerate after injury or resection by cell growth and division. During regeneration, the liver needs to maintain the essential metabolic tasks and meet the metabolic requirements for hepatocyte growth and division. Understanding the regulatory mechanisms involved in balancing the liver function and proliferation demand after injury or resection is crucial. In this study, we analyzed high-resolution temporal RNA sequencing data of liver regeneration after two-thirds partial hepatectomy (PHx) using network inference and mathematical modeling approaches. The reconstruction of the dynamic regulatory network of liver regeneration reveals the trajectories of different metabolic pathways, protein processing in the endoplasmic reticulum (ER), ribosome biogenesis, RNA transport, spliceosome, immune response, and cell cycle. We further developed a mathematical model of the integrated circuit of liver regeneration that accounts for underlying features of compensatory metabolism, proliferation, and epithelial-to-mesenchymal transition during liver regeneration. We show that a mutually exclusive behavior emerges due to the bistable inactivation of HNF4A, which controls the initiation and termination of liver regeneration and different population-level expressions observed in single-cell RNA sequencing data of liver regeneration.

scholarly journals Infiltrative tumour growth pattern correlates with poor outcome in oesophageal cancer

2020 ◽  
Vol 7 (1) ◽  
pp. e000431
Author(s):  
Maelle Anciaux ◽  
Pieter Demetter ◽  
Roland De Wind ◽  
Maria Gomez Galdon ◽  
Sylvie Vande Velde ◽  
...  
Keyword(s):  
Rna Sequencing ◽  
Oesophageal Cancer ◽  
Growth Pattern ◽  
Prognostic Value ◽  
Epithelial To Mesenchymal Transition ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Sequencing Data ◽  
Mesenchymal Transition

ObjectiveOesophageal cancer (OEC) is an aggressive disease with a poor survival rate. Prognostic markers are thus urgently needed. Due to the demonstrated prognostic value of histopathological growth pattern (HGP) in other cancers, we performed a retrospective assessment of HGP in patients suffering from invasive OEC.DesignA first cohort composed of 89 treatment-naïve operated patients with OEC from The Cancer Genome Atlas (TCGA) public database was constituted, from which H&E images and RNA-sequencing data were retrieved. Next, a second cohort composed of 99 patients with OEC treated and operated in a Belgian hospital was established. H&E-stained sections and extracted tumorous RNA were obtained from the samples. HGP were assessed on H&E slides as infiltrative (IGP) or expansive (EGP). TCGA RNA-sequencing data were analysed through the gene set enrichment analysis and Cytoscape softwares. Real-time quantitative PCR (qPCR) experiments were performed to assess gene expression in the Belgian cohort.ResultsIGP patients displayed a grim prognosis compared with EGP patients, while IGP was found as associated with numerous lymphovascular emboli and perinervous infiltrations. Analyses of the TCGA expression data showed that angiogenesis, epithelial-to-mesenchymal transition (EMT) and inflammation were significantly upregulated in IGP compared with EGP samples. qPCR experiments of three genes appearing as highly upregulated in each pathway showed no difference in expression according to the HGP.ConclusionThe current study demonstrates the poor prognostic value carried by IGP in OC and suggests angiogenesis, EMT and inflammation as key carcinogenetic pathways upregulated in this pattern.

scholarly journals Sex dependent gene activity in the human body

2020 ◽  
Author(s):  
Robin J.G. Hartman ◽  
Michal Mokry ◽  
Gerard Pasterkamp ◽  
Hester M. den Ruijter
Keyword(s):  
Sex Differences ◽  
Systems Biology ◽  
Human Body ◽  
Epithelial To Mesenchymal Transition ◽  
Tissue Expression ◽  
Gene Activity ◽  
Whole Body ◽  
Sequencing Data ◽  
Disease Etiology ◽  
Mesenchymal Transition

AbstractMany pathophysiological mechanisms in human health and disease are dependent on sex. Systems biology approaches are successfully used to decipher human disease etiology, yet the effect of sex on gene network biology is mostly unknown. To address this, we used RNA-sequencing data of over 700 individuals spanning 24 tissues from the Genotype-Tissue Expression project to generate a whole-body gene activity map and quantified the sex differences per tissue. We found that of the 13,787 genes analyzed in 24 tissues, 20.1% of the gene activity is influenced by sex. For example, skeletal muscle was predominantly enriched with genes more active in males, whereas thyroid primarily contained genes more active in females. This was accompanied by consistent sex differences in pathway activity, including hypoxia, epithelial-to-mesenchymal transition, and inflammation over the human body. Furthermore, multi-organ analyses revealed consistent sex-dependent gene activity over numerous tissues which was accompanied by enrichment of transcription factor binding motifs in the promoters of these genes. Finally, we show that many sex-biased genes are known druggable targets. This emphasizes sex as a biological variable and the need to incorporate sex in systems biology studies.

scholarly journals The altered transcriptome of pediatric myelodysplastic syndrome revealed by RNA sequencing

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Lorena Zubovic ◽  
Silvano Piazza ◽  
Toma Tebaldi ◽  
Luca Cozzuto ◽  
Giuliana Palazzo ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Myelodysplastic Syndrome ◽  
Rna Sequencing ◽  
Adaptive Immunity ◽  
Differentially Expressed Genes ◽  
Ribosome Biogenesis ◽  
Therapeutic Targets ◽  
Differentially Expressed ◽  
Sequencing Data ◽  
Aberrant Expression

Abstract Pediatric myelodysplastic syndrome (PMDS) is a very rare and still poorly characterized disorder. In this work, we identified novel potential targets of PMDS by determining genes with aberrant expression, which can be correlated with PMDS pathogenesis. We identified 291 differentially expressed genes (DEGs) in PMDS patients, comprising genes involved in the regulation of apoptosis and the cell cycle, ribosome biogenesis, inflammation and adaptive immunity. Ten selected DEGs were then validated, confirming the sequencing data. These DEGs will potentially represent new molecular biomarkers and therapeutic targets for PMDS.

scholarly journals Expression of Fibroblast Activation Protein Is Enriched in Neuroendocrine Prostate Cancer and Predicts Worse Survival

Genes ◽  
2022 ◽  
Vol 13 (1) ◽  
pp. 135
Author(s):  
Panagiotis J. Vlachostergios ◽  
Athanasios Karathanasis ◽  
Vassilios Tzortzis
Keyword(s):  
Prostate Cancer ◽  
Mrna Expression ◽  
Epithelial To Mesenchymal Transition ◽  
Fibroblast Activation Protein ◽  
Castration Resistant Prostate Cancer ◽  
Sequencing Data ◽  
Clinical Value ◽  
Mesenchymal Transition ◽  
Fibroblast Activation ◽  
Neuroendocrine Prostate Cancer

Background: Advanced prostate cancer (PC) may accumulate genomic alterations that hallmark lineage plasticity and transdifferentiation to a neuroendocrine (NE) phenotype. Fibroblast activation protein (FAP) is a key player in epithelial-to-mesenchymal transition (EMT). However, its clinical value and role in NE differentiation in advanced PC has not been fully investigated. Methods: Two hundred and eight patients from a multicenter, prospective cohort of patients with metastatic castration-resistant prostate cancer (CRPC) with available RNA sequencing data were analyzed for tumor FAP mRNA expression, and its association with overall survival (OS) and NE tumor features was investigated. Results: Twenty-one patients (10%) were found to have high FAP mRNA expression. Compared to the rest, this subset had a proportionally higher exposure to taxanes and AR signaling inhibitors (abiraterone or enzalutamide) and was characterized by active NE signaling, evidenced by high NEPC- and low AR-gene expression scores. These patients with high tumor mRNA FAP expression had a more aggressive clinical course and significantly shorter survival (12 months) compared to those without altered FAP expression (28 months, log-rank p = 0.016). Conclusions: FAP expression may serve as a valuable NE marker indicating a worse prognosis in patients with metastatic CRPC.

scholarly journals Sex-dependent gene co-expression in the human body

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Robin J. G. Hartman ◽  
Michal Mokry ◽  
Gerard Pasterkamp ◽  
Hester M. den Ruijter
Keyword(s):  
Sex Differences ◽  
Human Body ◽  
Gene Networks ◽  
Epithelial To Mesenchymal Transition ◽  
Tissue Expression ◽  
Whole Body ◽  
Sequencing Data ◽  
Disease Etiology ◽  
Mesenchymal Transition ◽  
Approved Drugs

AbstractMany pathophysiological mechanisms in human health and disease are dependent on sex. Systems biology approaches are successfully used to decipher human disease etiology, yet the effect of sex on gene network biology is mostly unknown. To address this, we used RNA-sequencing data of over 700 individuals spanning 24 tissues from the Genotype-Tissue Expression project to generate a whole-body gene co-expression map and quantified the sex differences per tissue. We found that of the 13,787 genes analyzed in 24 tissues, 29.5% of the gene co-expression is influenced by sex. For example, skeletal muscle was predominantly enriched with genes co-expressed stronger in males, whereas thyroid primarily contained genes co-expressed stronger in females. This was accompanied by consistent sex differences in pathway enrichment, including hypoxia, epithelial-to-mesenchymal transition, and inflammation over the human body. Furthermore, multi-organ analyses revealed consistent sex-dependent gene co-expression over numerous tissues which was accompanied by enrichment of transcription factor binding motifs in the promoters of these genes. Finally, we show that many sex-biased genes are associated with sex-biased diseases, such as autoimmunity and cancer, and more often the target of FDA-approved drugs than non-sexbiased genes. Our study suggests that sex affects biological gene networks by differences in gene co-expression and that attention to the effect of sex on biological responses to medical drugs is warranted.

Epithelial to mesenchymal transition in liver regeneration

2011 ◽  
Vol 49 (01) ◽  
Author(s):  
A Widera ◽  
G Campos ◽  
B Begher-Tibbe ◽  
G Günther ◽  
C Garcia-Perez ◽  
...  
Keyword(s):  
Liver Regeneration ◽  
Epithelial To Mesenchymal Transition ◽  
Mesenchymal Transition

scholarly journals Multiple hot-deck imputation for network inference from RNA sequencing data

2017 ◽  
Vol 34 (10) ◽  
pp. 1726-1732 ◽  
Author(s):  
Alyssa Imbert ◽  
Armand Valsesia ◽  
Caroline Le Gall ◽  
Claudia Armenise ◽  
Gregory Lefebvre ◽  
...  
Keyword(s):  
Rna Sequencing ◽  
Network Inference ◽  
Sequencing Data ◽  
Hot Deck Imputation

scholarly journals A comprehensive framework for analysis of microRNA sequencing data in metastatic colorectal cancer

NAR Cancer ◽  
2022 ◽  
Vol 4 (1) ◽  
Author(s):  
Eirik Høye ◽  
Bastian Fromm ◽  
Paul H M Böttger ◽  
Diana Domanska ◽  
Annette Torgunrud ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Epithelial To Mesenchymal Transition ◽  
Differential Expression Analysis ◽  
Metastatic Progression ◽  
Sequencing Data ◽  
Bioinformatics Pipeline ◽  
Mesenchymal Transition ◽  
Starting Point ◽  
Microrna Sequencing ◽  
Metastatic Sites

ABSTRACT Although microRNAs (miRNAs) contribute to all hallmarks of cancer, miRNA dysregulation in metastasis remains poorly understood. The aim of this work was to reliably identify miRNAs associated with metastatic progression of colorectal cancer (CRC) using novel and previously published next-generation sequencing (NGS) datasets generated from 268 samples of primary (pCRC) and metastatic CRC (mCRC; liver, lung and peritoneal metastases) and tumor adjacent tissues. Differential expression analysis was performed using a meticulous bioinformatics pipeline, including only bona fide miRNAs, and utilizing miRNA-tailored quality control and processing. Five miRNAs were identified as up-regulated at multiple metastatic sites Mir-210_3p, Mir-191_5p, Mir-8-P1b_3p [mir-141–3p], Mir-1307_5p and Mir-155_5p. Several have previously been implicated in metastasis through involvement in epithelial-to-mesenchymal transition and hypoxia, while other identified miRNAs represent novel findings. The use of a publicly available pipeline facilitates reproducibility and allows new datasets to be added as they become available. The set of miRNAs identified here provides a reliable starting-point for further research into the role of miRNAs in metastatic progression.

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