Browsing by Author "Yu, Xueping"
Now showing 1 - 2 of 2
Results Per Page
Sort Options
- ItemCharacterization of chemically induced liver injuries using gene co-expression modules.(2014-09-17) Tawa, Gregory J; AbdulHameed, Mohamed Diwan M; Yu, Xueping; Kumar, Kamal; Ippolito, Danielle L; Lewis, John A; Stallings, Jonathan D; Wallqvist, AndersLiver injuries due to ingestion or exposure to chemicals and industrial toxicants pose a serious health risk that may be hard to assess due to a lack of non invasive diagnostic tests Mapping chemical injuries to organ specific damage and clinical outcomes via biomarkers or biomarker panels will provide the foundation for highly specific and robust diagnostic tests Here we have used DrugMatrix a toxicogenomics database containing organ specific gene expression data matched to dose dependent chemical exposures and adverse clinical pathology assessments in Sprague Dawley rats to identify groups of co expressed genes modules specific to injury endpoints in the liver We identified 78 such gene co expression modules associated with 25 diverse injury endpoints categorized from clinical pathology organ weight changes and histopathology Using gene expression data associated with an injury condition we showed that these modules exhibited different patterns of activation characteristic of each injury We further showed that specific module genes mapped to 1 known biochemical pathways associated with liver injuries and 2 clinically used diagnostic tests for liver fibrosis As such the gene modules have characteristics of both generalized and specific toxic response pathways Using these results we proposed three gene signature sets characteristic of liver fibrosis steatosis and general liver injury based on genes from the co expression modules Out of all 92 identified genes 18 20 genes have well documented relationships with liver disease whereas the rest are novel and have not previously been associated with liver disease In conclusion identifying gene co expression modules associated with chemically induced liver injuries aids in generating testable hypotheses and has the potential to identify putative biomarkers of adverse health effects
- ItemA systems biology strategy to identify molecular mechanisms of action and protein indicators of traumatic brain injury.(2014-12-17) Yu, Chenggang; Boutté, Angela; Yu, Xueping; Dutta, Bhaskar; Feala, Jacob D; Schmid, Kara; Dave, Jitendra; Tawa, Gregory J; Wallqvist, Anders; Reifman, JaquesThe multifactorial nature of traumatic brain injury TBI especially the complex secondary tissue injury involving intertwined networks of molecular pathways that mediate cellular behavior has confounded attempts to elucidate the pathology underlying the progression of TBI Here systems biology strategies are exploited to identify novel molecular mechanisms and protein indicators of brain injury To this end we performed a meta analysis of four distinct high throughput gene expression studies involving different animal models of TBI By using canonical pathways and a large human protein interaction network as a scaffold we separately overlaid the gene expression data from each study to identify molecular signatures that were conserved across the different studies At 24 hr after injury the significantly activated molecular signatures were nonspecific to TBI whereas the significantly suppressed molecular signatures were specific to the nervous system In particular we identified a suppressed subnetwork consisting of 58 highly interacting coregulated proteins associated with synaptic function We selected three proteins from this subnetwork postsynaptic density protein 95 nitric oxide synthase 1 and disrupted in schizophrenia 1 and hypothesized that their abundance would be significantly reduced after TBI In a penetrating ballistic like brain injury rat model of severe TBI Western blot analysis confirmed our hypothesis In addition our analysis recovered 12 previously identified protein biomarkers of TBI The results suggest that systems biology may provide an efficient high yield approach to generate testable hypotheses that can be experimentally validated to identify novel mechanisms of action and molecular indicators of TBI