Similar Datasets
Project description:A single administration of an iodine thyroid blocking agent is usually sufficient to protect thyroid from radioactive iodine and prevent thyroid cancer. Repeated administration of stable iodine (rKI) may be necessary during prolonged or repeated exposure to radioactive iodine. We previously showed that rKI for eight days offers protection without toxic effects in adult rats. However, the effect of rKI administration in the developing foetus is unknown, especially on brain development, although a correlation between impaired maternal thyroid status and a decrease in intelligence quotient of the progeny has been observed. This study revealed distinct gene expression profiles between the progeny of rats receiving either rKI or saline during pregnancy. To understand the implication of these differentially expressed (DE) genes, a systems biology approach was used to construct networks for each organ using three different techniques: Bayesian statistics, sPLS-DA and manual construction of a Process Descriptive (PD) network. The PD network showed DE genes from both organs participating in the same cellular processes that affect mitophagy and neuronal outgrowth. This work may help to evaluate the doctrine for using rKI in case of repetitive or prolonged exposure to radioactive particles upon nuclear accidents.
| S-EPMC7331645 | biostudies-literature
Project description:Our group showed that repetitive dose of KI for eight days offers efficient protection against radiation exposure during nuclear accidents without toxic effects in adult rats. However, the effect of repetitive KI on the developing fetus still unknown especially on brain development, but a correlation between the impaired maternal thyroid status and a decrease in intelligence quotient has been observed. In this study, gene expression analysis of the progeny of repetitive KI-administered pregnant rats performed by our group showed distinct gene expression profile from two different organs: thyroid and cortex. To understand how these differentially expressed genes are implicated in the observed behaviour change, a systems biology approach was used to construct networks using three different techniques; Bayesian statistics using ShrinkNet, sPLS-DA on the DIABLO platform using mixOmics and manual construction of a Process Descriptive network. For each organ, we were able to construct gene expression network, to select genes that are most contributing to either control or KI-treated groups, respectively, and to construct the PD network from differentially expressed (DE) gene enriched with data from publications. Furthermore, we were able to connect DE genes from both organs into one network with genes from both organ participating in the same cellular processes that affect mitophagy and neuronal outgrowth.
2020-05-30 | GSE148253 | GEO
Project description:Our group showed that repetitive dose of KI for eight days offers efficient protection against radiation exposure during nuclear accidents without toxic effects in adult rats. However, the effect of repetitive KI on the developing fetus still unknown especially on brain development, but a correlation between the impaired maternal thyroid status and a decrease in intelligence quotient has been observed. In this study, gene expression analysis of the progeny of repetitive KI-administered pregnant rats performed by our group showed distinct gene expression profile from two different organs: thyroid and cortex. To understand how these differentially expressed genes are implicated in the observed behaviour change, a systems biology approach was used to construct networks using three different techniques; Bayesian statistics using ShrinkNet, sPLS-DA on the DIABLO platform using mixOmics and manual construction of a Process Descriptive network. For each organ, we were able to construct gene expression network, to select genes that are most contributing to either control or KI-treated groups, respectively, and to construct the PD network from differentially expressed (DE) gene enriched with data from publications. Furthermore, we were able to connect DE genes from both organs into one network with genes from both organ participating in the same cellular processes that affect mitophagy and neuronal outgrowth.
2020-05-30 | GSE148280 | GEO
Project description:Effects of repetitive Iodine Thyroid Blocking on the Foetal Brain and Thyroid in rats: a Systems Biology approach
| PRJNA623724 | ENA
Project description:Effects of repetitive Iodine Thyroid Blocking on the Fetal Brain and Thyroid in rats: a Systems Biology approach [Thyroid]
| PRJNA623596 | ENA
Project description:Effects of repetitive Iodine Thyroid Blocking on the Fetal Brain and Thyroid in rats: a Systems Biology approach [Cortex]
| PRJNA623727 | ENA
Project description:Traumatic brain injury (TBI) represents a critical health problem of which diagnosis, management, and treatment remain challenging. TBI is a contributing factor in approximately one-third of all injury-related deaths in the United States. The Centers for Disease Control and Prevention estimate that 1.7 million people suffer a TBI in the United States annually. Efforts continue to focus on elucidating the complex molecular mechanisms underlying TBI pathophysiology and defining sensitive and specific biomarkers that can aid in improving patient management and care. Recently, the area of neuroproteomics-systems biology is proving to be a prominent tool in biomarker discovery for central nervous system injury and other neurological diseases. In this work, we employed the controlled cortical impact (CCI) model of experimental TBI in rat model to assess the temporal-global proteome changes after acute (1?day) and for the first time, subacute (7?days), post-injury time frame using the established cation-anion exchange chromatography-1D SDS gel electrophoresis LC-MS/MS platform for protein separation combined with discrete systems biology analyses to identify temporal biomarker changes related to this rat TBI model. Rather than focusing on any one individual molecular entity, we used in silico systems biology approach to understand the global dynamics that govern proteins that are differentially altered post-injury. In addition, gene ontology analysis of the proteomic data was conducted in order to categorize the proteins by molecular function, biological process, and cellular localization. Results show alterations in several proteins related to inflammatory responses and oxidative stress in both acute (1?day) and subacute (7?days) periods post-TBI. Moreover, results suggest a differential upregulation of neuroprotective proteins at 7?days post-CCI involved in cellular functions such as neurite growth, regeneration, and axonal guidance. Our study is among the first to assess temporal neuroproteome changes in the CCI model. Data presented here unveil potential neural biomarkers and therapeutic targets that could be used for diagnosis, for treatment and, most importantly, for temporal prognostic assessment following brain injury. Of interest, this work relies on in silico bioinformatics approach to draw its conclusion; further work is conducted for functional studies to validate and confirm the omics data obtained.
| S-EPMC5118702 | biostudies-literature
Project description:The standard drug development model uses reductionist approaches to discover small molecules targeting one pathway. Although systems biology analyzes multiple pathways, the approach is often used to develop a small molecule interacting at only one pathway in the system. Similar to that in physics where a departure from the old reductionist "Copenhagen View" of quantum physics to a new and predictive systems based, collective model has emerged yielding new breakthroughs such as the LASER, a new model is emerging in biology where systems biology is used to develop a new technology acting at multiple pathways called "systems therapeutics."
| S-EPMC4027758 | biostudies-other
Project description:Autism is the fastest growing developmental disorder in the world today. The prevalence of autism in the US has risen from 1 in 2500 in 1970 to 1 in 88 children today. People with autism present with repetitive movements and with social and communication impairments. These impairments can range from mild to profound. The estimated total lifetime societal cost of caring for one individual with autism is $3.2 million US dollars. With the rapid growth in this disorder and the great expense of caring for those with autism, it is imperative for both individuals and society that techniques be developed to model and understand autism. There is increasing evidence that those individuals diagnosed with autism present with highly diverse set of abnormalities affecting multiple systems of the body. To this date, little to no work has been done using a whole body systems biology approach to model the characteristics of this disorder. Identification and modelling of these systems might lead to new and improved treatment protocols, better diagnosis and treatment of the affected systems, which might lead to improved quality of life by themselves, and, in addition, might also help the core symptoms of autism due to the potential interconnections between the brain and nervous system with all these other systems being modeled. This paper first reviews research which shows that autism impacts many systems in the body, including the metabolic, mitochondrial, immunological, gastrointestinal and the neurological. These systems interact in complex and highly interdependent ways. Many of these disturbances have effects in most of the systems of the body. In particular, clinical evidence exists for increased oxidative stress, inflammation, and immune and mitochondrial dysfunction which can affect almost every cell in the body. Three promising research areas are discussed, hierarchical, subgroup analysis and modeling over time. This paper reviews some of the systems disturbed in autism and suggests several systems biology research areas. Autism poses a rich test bed for systems biology modeling techniques.
| S-EPMC3507704 | biostudies-literature
Project description:Background Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents. The survival rate of patients with metastatic disease remains very dismal. Nevertheless, metastasis is a complex process and a single-level analysis is not likely to identify its key biological determinants. In this study, we used a systems biology approach to identify common metastatic pathways that are jointly supported by both mRNA and protein expression data in two distinct human metastatic OS models. Results mRNA expression microarray and N-linked glycoproteomic analyses were performed on two commonly used isogenic pairs of human metastatic OS cell lines, namely HOS/143B and SaOS-2/LM7. Pathway analysis of the differentially regulated genes and glycoproteins separately revealed pathways associated to metastasis including cell cycle regulation, immune response, and epithelial-to-mesenchymal-transition. However, no common significant pathway was found at both genomic and proteomic levels between the two metastatic models, suggesting a very different biological nature of the cell lines. To address this issue, we used a topological significance analysis based on a “shortest path” algorithm to identify topological nodes, which uncovered additional biological information with respect to the genomic and glycoproteomic profiles but remained hidden from the direct analyses. Pathway analysis of the significant topological nodes revealed a striking concordance between the models and identified significant common pathways, including “Cytoskeleton remodeling/TGF/WNT”, “Cytoskeleton remodeling/Cytoskeleton remodeling”, and “Cell adhesion/Chemokines and adhesion”. Of these, the “Cytoskeleton remodeling/TGF/WNT” was the top ranked common pathway from the topological analysis of the genomic and proteomic profiles in the two metastatic models. The up-regulation of proteins in the “Cytoskeleton remodeling/TGF/WNT” pathway in the SaOS-2/LM7 and HOS/143B models was further validated using an orthogonal Reverse Phase Protein Array platform. Conclusions In this study, we used a systems biology approach by integrating genomic and proteomic data to identify key and common metastatic mechanisms in OS. The use of the topological analysis revealed hidden biological pathways that are known to play critical roles in metastasis. Wnt signaling has been previously implicated in OS and other tumors, and inhibitors of Wnt signaling pathways are available for clinical testing. Further characterization of this common pathway and other topological pathways identified from this study may lead to a novel therapeutic strategy for the treatment of metastatic OS.
2012-04-25 | GSE37552 | GEO