Extracting proteins involved in disease progression using temporally connected networks

Anand, Rajat; Sarmah, Dipanka Tanu; Chatterjee, Samrat

doi:10.1186/s12918-018-0600-z

Cited by 10 publications

(8 citation statements)

References 23 publications

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“…To control the entire network, it is important to identify subsets of nodes that, when controlled by distinct signals, are capable of driving the network. These nodes are named as driver nodes in the literature (77–79). According to the controllability rank condition of Kalman (80, 81), the system described by Eq.…”

Section: Methodsmentioning

confidence: 99%

Bidirectional regulation between AP-1 and SUMO genes modulates inflammatory signalling duringSalmonellaTyphimurium infection

Kumar

Soory

Mustfa

et al. 2022

Preprint

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Gram-negative bacterium Salmonella Typhimurium ( STm ) is the causative agent of gastroenteritis. Among the various gut pathogens, STm is still one of the most frequent culprits posing a significant health challenge. STm utilizes its effector proteins to highjack host cell processes. Alteration of SUMOylation, a post-translational modification mechanism, is one such change caused by STm. STm mediated simultaneous downregulation of SUMO-pathway genes, Ubc9 and PIAS1, is required for an efficient infection. In the present study, the regulation of SUMO pathway genes during STm infection was investigated. Promoters of both UBC9 and PIAS1, were seen to harbor binding motifs of AP-1, Activator protein-1 (c-Jun:c-Fos heterodimers or c-Jun:c-Jun homodimers). Using electrophoretic mobility shift assays, a direct binding of c-Fos to the identified motifs was observed. Perturbation of c-Fos led to changes in expression of Ubc9 and PIAS1, while its SUMO-modifications resulted in differential regulation of its target genes. In line with this, STm infection of fibroblasts with SUMOylation deficient c-Fos (c-FOS-KO SUMO-def-FOS ) resulted in uncontrolled activation of target genes, as revealed by 3’mRNA-Seq analysis and mathematical modelling, resulting in massive activation of inflammatory pathways. Infection of c-FOS-KO SUMO-def-FOS cells favored STm replication, indicating misdirected immune mechanisms in these cells. Finally, chromatin Immuno-precipitation assays confirmed a context dependent differential binding and release of AP-1 to/from target genes due to its Phosphorylation and SUMOylation respectively. Overall, our data point towards existence of a bidirectional cross-talk between c-Fos and the SUMO pathway and highlighting its importance in AP-1 function relevant to STm infections and beyond.

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Section: Methodsmentioning

confidence: 99%

Bidirectional regulation between AP-1 and SUMO genes modulates inflammatory signalling duringSalmonellaTyphimurium infection

Kumar

Soory

Mustfa

et al. 2022

Preprint

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Section: (D) Control Theory Analysismentioning

confidence: 99%

Bidirectional regulation between AP-1 and SUMOylation pathway genes modulates inflammatory signaling duringSalmonellainfection

Kumar

Soory

Mustfa

et al. 2022

Journal of Cell Science

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Post-translational modifications (PTMs), such as SUMOylation, are known to modulate fundamental processes of a cell. Infectious agents such as Salmonella Typhimurium (STm) that causes gastroenteritis, utilizes PTM mechanism SUMOylation to highjack host cell. STm suppresses host SUMO-pathway genes Ubc9 and PIAS1 to perturb SUMOylation for an efficient infection. In the present study, the regulation of SUMO-pathway genes during STm infection was investigated. A direct binding of c-Fos, a component of AP-1 (Activator Protein-1), to promoters of both UBC9 and PIAS1 was observed. Experimental perturbation of c-Fos led to changes in expression of both Ubc9 and PIAS1. STm infection of fibroblasts with SUMOylation deficient c-Fos (c-FOS-KOSUMO-def-FOS) resulted in uncontrolled activation of target genes, resulting in massive immune activation. Infection of c-FOS-KOSUMO-def-FOS cells favored STm replication, indicating misdirected immune mechanisms. Finally, chromatin Immuno-precipitation assays confirmed a context dependent differential binding and release of AP-1 to/from target genes due to its Phosphorylation and SUMOylation respectively. Overall, our data point towards existence of a bidirectional cross-talk between c-Fos and the SUMO pathway and highlighting its importance in AP-1 function relevant to STm infection and beyond.

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“…From a network analysis perspective, temporal analysis of genes is done in diseases like obesity [ 100 ], but none has been reported in autophagy. Such a study will help to decipher the change in behavior of ATG with respect to time and identify potential drug targets.…”

Section: Future Directionmentioning

confidence: 99%

Tracing the footsteps of autophagy in computational biology

Sarmah

Bairagi

Chatterjee

2020

Briefings in Bioinformatics

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Autophagy plays a crucial role in maintaining cellular homeostasis through the degradation of unwanted materials like damaged mitochondria and misfolded proteins. However, the contribution of autophagy toward a healthy cell environment is not only limited to the cleaning process. It also assists in protein synthesis when the system lacks the amino acids’ inflow from the extracellular environment due to diet consumptions. Reduction in the autophagy process is associated with diseases like cancer, diabetes, non-alcoholic steatohepatitis, etc., while uncontrolled autophagy may facilitate cell death. We need a better understanding of the autophagy processes and their regulatory mechanisms at various levels (molecules, cells, tissues). This demands a thorough understanding of the system with the help of mathematical and computational tools. The present review illuminates how systems biology approaches are being used for the study of the autophagy process. A comprehensive insight is provided on the application of computational methods involving mathematical modeling and network analysis in the autophagy process. Various mathematical models based on the system of differential equations for studying autophagy are covered here. We have also highlighted the significance of network analysis and machine learning in capturing the core regulatory machinery governing the autophagy process. We explored the available autophagic databases and related resources along with their attributes that are useful in investigating autophagy through computational methods. We conclude the article addressing the potential future perspective in this area, which might provide a more in-depth insight into the dynamics of autophagy.

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Extracting proteins involved in disease progression using temporally connected networks

Cited by 10 publications

References 23 publications

Bidirectional regulation between AP-1 and SUMO genes modulates inflammatory signalling duringSalmonellaTyphimurium infection

Bidirectional regulation between AP-1 and SUMO genes modulates inflammatory signalling duringSalmonellaTyphimurium infection

Bidirectional regulation between AP-1 and SUMOylation pathway genes modulates inflammatory signaling duringSalmonellainfection

Tracing the footsteps of autophagy in computational biology

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