scholarly journals The Gene Coexpression Analysis Identifies Functional Modules Dynamically Changed After Traumatic Brain Injury

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Zhi-jie Zhao ◽  
Dong-po Wei ◽  
Rui-zhe Zheng ◽  
Tinghua Peng ◽  
Xiang Xiao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Cell Activation ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Protein Translation ◽  
Functional Modules ◽  
Coexpression Analysis ◽  
Gene Coexpression

Traumatic brain injury (TBI) is a major cause of morbidity and mortality, both in adult and pediatric populations. However, the dynamic changes of gene expression profiles following TBI have not been fully understood. In this study, we identified the differentially expressed genes (DEGs) following TBI. Remarkably, Serpina3n, Asf1b, Folr1, LOC100366216, Clec12a, Olr1, Timp1, Hspb1, Lcn2, and Spp1 were identified as the top 10 with the highest statistical significance. The weighted gene coexpression analysis (WGCNA) identified 12 functional modules from the DEGs, which showed specific expression patterns over time and were characterized by enrichment analysis. Specifically, the black and turquoise modules were mainly involved in energy metabolism and protein translation. The green yellow and yellow modules including Hmox1, Mif, Anxa2, Timp1, Gfap, Cd9, Gja1, Pdpn, and Gpx1 were related to response to wounding, indicating that expression of these genes such as Hmox1, Anxa2, and Timp1 could protect the brains from brain injury. The green yellow module highlighted genes involved in microglial cell activation such as Tyrobp, Cx3cr1, Grn, Trem2, C1qa, and Aif1, suggesting that these genes were responsible for the inflammatory response caused by TBI. The upregulation of these genes has been validated in an independent dataset. These results indicated that the key genes in microglia cell activation may serve as a promising therapeutic target for TBI. In summary, the present study provided a full view of the dynamic gene expression changes following TBI.

scholarly journals The role of salivary vesicles as a potential inflammatory biomarker to detect traumatic brain injury in mixed martial artists

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rani Matuk ◽  
Mandy Pereira ◽  
Janette Baird ◽  
Mark Dooner ◽  
Yan Cheng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Head Injury ◽  
Injury Severity ◽  
Expression Profiles ◽  
High Impact ◽  
Impact Mechanism ◽  
Inflammatory Biomarker ◽  
Potential Biomarker

AbstractTraumatic brain injury (TBI) is of significant concern in the realm of high impact contact sports, including mixed martial arts (MMA). Extracellular vesicles (EVs) travel between the brain and oral cavity and may be isolated from salivary samples as a noninvasive biomarker of TBI. Salivary EVs may highlight acute neurocognitive or neuropathological changes, which may be particularly useful as a biomarker in high impact sports. Pre and post-fight samples of saliva were isolated from 8 MMA fighters and 7 from controls. Real-time PCR of salivary EVs was done using the TaqMan Human Inflammatory array. Gene expression profiles were compared pre-fight to post-fight as well as pre-fight to controls. Largest signals were noted for fighters sustaining a loss by technical knockout (higher impact mechanism of injury) or a full match culminating in referee decision (longer length of fight), while smaller signals were noted for fighters winning by joint or choke submission (lower impact mechanism as well as less time). A correlation was observed between absolute gene information signals and fight related markers of head injury severity. Gene expression was also significantly different in MMA fighters pre-fight compared to controls. Our findings suggest that salivary EVs as a potential biomarker in the acute period following head injury to identify injury severity and can help elucidate pathophysiological processes involved in TBI.

scholarly journals What Do Machines Tell us About Dementia? Machine Learning Applied to Aging, Dementia and Traumatic Brain Injury Study

2021 ◽  
Author(s):  
Denis Arthur Pinheiro Moura ◽  
Joao Ricardo Mendes de Oliveira
Keyword(s):  
Gene Expression ◽  
Machine Learning ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Expression Profiles ◽  
Brain Regions ◽  
Machine Learning Algorithms ◽  
Differentially Expressed ◽  
Classification Model ◽  
Specific Gene

Abstract Dementia, a syndrome characterized by the progressive deterioration of memory and cognition, arises from different pathologies, with Alzheimer's Disease (AD) its most common cause. Patterns of gene expression during dementia of different etiologies may function as generalist biomarkers of the condition. We used RNA-Seq data from the Allen Dementia and Traumatic Brain Injury Study (ADTBI) to identify differentially expressed genes in brains with dementia. Machine Learning algorithms Decision Trees (DT) and Random Forest (RF) were used to create models to identify dementia samples based on their gene expression profile. Importance analyses were conducted to identify the most relevant genes in each classification model. A total of 1629 differentially expressed (DE) genes were found in brains with the condition. Gene PAN3-AS1 was the only DE gene across more than three brain regions. The artificial intelligence models were capable of identifying correctly up to 92.85% of dementia samples. Our analyses provide interesting insights regarding using brain-specific gene expression profiles as biomarkers of dementia, identifying genes possibly involved with dementia, and guiding future studies in prediction and early identification of the syndrome.

scholarly journals Gene expression patterns following unilateral traumatic brain injury reveals a local pro-inflammatory and remote anti-inflammatory response

BMC Genomics ◽  
2013 ◽  
Vol 14 (1) ◽  
pp. 282 ◽  
Author(s):  
Todd E White ◽  
Gregory D Ford ◽  
Monique C Surles-Zeigler ◽  
Alicia S Gates ◽  
Michelle C LaPlaca ◽  
...  
Keyword(s):  
Gene Expression ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Inflammatory Response ◽  
Expression Patterns ◽  
Gene Expression Patterns ◽  
Anti Inflammatory

scholarly journals Systems spatiotemporal dynamics of traumatic brain injury at single cell resolution reveals humanin as a therapeutic target

2021 ◽  
Author(s):  
Douglas Arneson ◽  
Guanglin Zhang ◽  
In Sook Ahn ◽  
Zhe Ying ◽  
Graciel Diamante ◽  
...  
Keyword(s):  
Gene Expression ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Frontal Cortex ◽  
Single Cell ◽  
Target Genes ◽  
Expression Patterns ◽  
Brain Regions ◽  
Cellular Heterogeneity ◽  
Blood Leukocytes

Abstract The etiology of mild traumatic brain injury (mTBI) remains elusive due to the tissue and cellular heterogeneity of the affected brain regions that underlie cognitive impairments and subsequent neurological disorders. This complexity is further exacerbated by disrupted circuits within and between cell populations across brain regions and the periphery, which occur at different timescales and in spatial domains. We profiled three tissues (hippocampus, frontal cortex, and blood leukocytes) at the acute (24hr) and chronic (7days) phases of mTBI at single cell resolution and demonstrated that the coordinated gene expression patterns across cell types were disrupted and re-organized by TBI at different timescales with distinct regional and cellular patterns. Gene expression-based network modeling identified astrocytes as a key regulator of the cell-cell coordination following mTBI in both hippocampus and frontal cortex across timepoints, and mt-Rnr2, which encodes the mitochondrial peptide humanin, as a potential target for intervention based on its broad regional and dynamic dysregulation following mTBI. Treatment of a murine mTBI model with humanin reversed cognitive impairment caused by mTBI through the restoration of metabolic pathways within astrocytes. Our results offer a systems-level understanding of the dynamic and spatial regulation of gene programs by mTBI and pinpoint key target genes, pathways, and cell circuits that are amenable to therapeutics.

Persistent Inflammatory Pathways Associated with Early Onset Myocardial Infarction in a Medicated Multiethnic Hawaiian Cohort

2011 ◽  
Vol 4 ◽  
pp. BCI.S6976 ◽  
Author(s):  
Kornelia M. Szauter ◽  
Matthias K. Jansen ◽  
Gordon Okimoto ◽  
Michael Loomis ◽  
James H. Kimura ◽  
...  
Keyword(s):  
Gene Expression ◽  
Myocardial Infarction ◽  
T Cell Activation ◽  
Cell Activation ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Medical Intervention ◽  
Vascular Pathology ◽  
Functional Evaluation ◽  
Current Standard

In spite of current standard therapies to target the major pathomechanisms in myocardial infarction (MI), inflammatory gene expression patterns have been consistently revealed in MI patients. In a multiethnic cohort, we aimed to identify MI-associated pathomechanisms that may be unresponsive to medical treatment to improve diagnosis and therapy. Gene expression profiles in whole blood were analyzed in medicated Asian, African American and Caucasian patients living in Hawaii with a history of early MI and age, ethnicity, risk factor and medication-matched controls. PANTHER ontological and Ingenuity Pathway analysis and functional evaluation of the consistently differentially expressed genes identified coordinated up-regulation of genes for inflammation (LGALS3, PTX3, ZBTB32, BCL2L1), T-cell activation (IL12RB1, VAV3, JAG1, CAMP), immune imbalance (IL-8, IL2RA, CCR7, AHNAK), and active atherosclerosis (NR1H4, BIN1, GSTT1, MARCO) that persist in MI patients in spite of concerted treatment efforts to control vascular pathology. Furthermore, significant ethnic differences appear to exist within the active disease mechanisms that need to be further investigated to identify key targets for effective medical intervention.

Gene expression following traumatic brain injury in humans: analysis by microarray

2005 ◽  
Vol 12 (3) ◽  
pp. 284-290 ◽  
Author(s):  
Daniel B. Michael ◽  
Donna M. Byers ◽  
Louis N. Irwin
Keyword(s):  
Gene Expression ◽  
Traumatic Brain Injury ◽  
Brain Injury

scholarly journals Comprehensive Comparison of Amnion Stromal Cells and Chorion Stromal Cells by RNA-Seq

2021 ◽  
Vol 22 (4) ◽  
pp. 1901
Author(s):  
Brielle Jones ◽  
Chaoyang Li ◽  
Min Sung Park ◽  
Anne Lerch ◽  
Vimal Jacob ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stromal Cells ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Principal Component ◽  
Differentially Expressed ◽  
Inflammatory Factor ◽  
Next Generation Sequencing Technology ◽  
Angiogenic Potential ◽  
Anti Inflammatory

Mesenchymal stromal cells derived from the fetal placenta, composed of an amnion membrane, chorion membrane, and umbilical cord, have emerged as promising sources for regenerative medicine. Here, we used next-generation sequencing technology to comprehensively compare amniotic stromal cells (ASCs) with chorionic stromal cells (CSCs) at the molecular and signaling levels. Principal component analysis showed a clear dichotomy of gene expression profiles between ASCs and CSCs. Unsupervised hierarchical clustering confirmed that the biological repeats of ASCs and CSCs were able to respectively group together. Supervised analysis identified differentially expressed genes, such as LMO3, HOXA11, and HOXA13, and differentially expressed isoforms, such as CXCL6 and HGF. Gene Ontology (GO) analysis showed that the GO terms of the extracellular matrix, angiogenesis, and cell adhesion were significantly enriched in CSCs. We further explored the factors associated with inflammation and angiogenesis using a multiplex assay. In comparison with ASCs, CSCs secreted higher levels of angiogenic factors, including angiogenin, VEGFA, HGF, and bFGF. The results of a tube formation assay proved that CSCs exhibited a strong angiogenic function. However, ASCs secreted two-fold more of an anti-inflammatory factor, TSG-6, than CSCs. In conclusion, our study demonstrated the differential gene expression patterns between ASCs and CSCs. CSCs have superior angiogenic potential, whereas ASCs exhibit increased anti-inflammatory properties.

scholarly journals Chronic complement dysregulation drives neuroinflammation after traumatic brain injury: a transcriptomic study

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Amer Toutonji ◽  
Mamatha Mandava ◽  
Silvia Guglietta ◽  
Stephen Tomlinson
Keyword(s):  
Gene Expression ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Complement System ◽  
Classical Pathway ◽  
Post Injury ◽  
Complement Inhibition ◽  
Time Points ◽  
Complement Gene ◽  
The Complement System

AbstractActivation of the complement system propagates neuroinflammation and brain damage early and chronically after traumatic brain injury (TBI). The complement system is complex and comprises more than 50 components, many of which remain to be characterized in the normal and injured brain. Moreover, complement therapeutic studies have focused on a limited number of histopathological outcomes, which while informative, do not assess the effect of complement inhibition on neuroprotection and inflammation in a comprehensive manner. Using high throughput gene expression technology (NanoString), we simultaneously analyzed complement gene expression profiles with other neuroinflammatory pathway genes at different time points after TBI. We additionally assessed the effects of complement inhibition on neuropathological processes. Analyses of neuroinflammatory genes were performed at days 3, 7, and 28 post injury in male C57BL/6 mice following a controlled cortical impact injury. We also characterized the expression of 59 complement genes at similar time points, and also at 1- and 2-years post injury. Overall, TBI upregulated the expression of markers of astrogliosis, immune cell activation, and cellular stress, and downregulated the expression of neuronal and synaptic markers from day 3 through 28 post injury. Moreover, TBI upregulated gene expression across most complement activation and effector pathways, with an early emphasis on classical pathway genes and with continued upregulation of C2, C3 and C4 expression 2 years post injury. Treatment using the targeted complement inhibitor, CR2-Crry, significantly ameliorated TBI-induced transcriptomic changes at all time points. Nevertheless, some immune and synaptic genes remained dysregulated with CR2-Crry treatment, suggesting adjuvant anti-inflammatory and neurotropic therapy may confer additional neuroprotection. In addition to characterizing complement gene expression in the normal and aging brain, our results demonstrate broad and chronic dysregulation of the complement system after TBI, and strengthen the view that the complement system is an attractive target for TBI therapy.

scholarly journals Discovering Distinct Patterns in Gene Expression Profiles

2008 ◽  
Vol 5 (2) ◽  
Author(s):  
Li Teng ◽  
Laiwan Chan
Keyword(s):  
Gene Expression ◽  
Large Scale ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Gene Expression Profiles ◽  
Clustering Methods ◽  
Gene Expressions ◽  
Real Gene ◽  
Large Scale Dataset ◽  
Coexpressed Genes

SummaryTraditional analysis of gene expression profiles use clustering to find groups of coexpressed genes which have similar expression patterns. However clustering is time consuming and could be diffcult for very large scale dataset. We proposed the idea of Discovering Distinct Patterns (DDP) in gene expression profiles. Since patterns showing by the gene expressions reveal their regulate mechanisms. It is significant to find all different patterns existing in the dataset when there is little prior knowledge. It is also a helpful start before taking on further analysis. We propose an algorithm for DDP by iteratively picking out pairs of gene expression patterns which have the largest dissimilarities. This method can also be used as preprocessing to initialize centers for clustering methods, like K-means. Experiments on both synthetic dataset and real gene expression datasets show our method is very effective in finding distinct patterns which have gene functional significance and is also effcient.

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