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Ge, W.

Publications and source records attributed to Ge, W..

3 recordsLinked to original sources

Systems Biology Understanding of the Effects of Lithium on Cancer.

Lithium has many widely varying biochemical and phenomenological effects, suggesting that a systems biology approach is required to understand its action. Multiple lines of evidence point to lithium as a significant factor in development of cancer, showing that understanding lithium action is of high importance. In this paper we undertake first steps towards a systems approach by analyzing mutual enrichment between the interactomes of lithium-sensitive enzymes and the pathways associated with cancer. This work integrates information from two important databases, STRING and KEGG pathways. We find that for the majority of cancer pathways the mutual enrichment is many times greater than chance, reinforcing previous lines of evidence that lithium is an important influence on cancer.

cancer biology

PRL-1 is required for neuroprotection against olfactory CO2 stimulation in Drosophila

The Mammalian phosphatase of regenerating liver (PRL) family is primarily recognized for its oncogenic properties. Here we found that in Drosophila, loss of prl-1 resulted in CO2-induced brain disorder presented as irreversible wing hold up with enhancement of Ca2+ responses at the neuron synaptic terminals. Overexpression of Prl-1 in the nervous system could rescue the mutant phenotype. We show that Prl-1 is particularly expressed in CO2-responsive neural circuit and the higher brain centers. Ablation of the CO2 olfactory receptor, Gr21a, suppressed the mutant phenotype, suggesting that CO2 acts as a neuropathological substrate in absence of Prl-1. Further studies found that the wing hold up is an obvious consequence upon knockdown of Uex, a magnesium transporter, which directly interacts with Prl-1. Conditional expression of Uex in the nervous system could rescue the phenotype of prl-1 mutants. We demonstrate that Uex acts genetically downstream of Prl-1. Our findings provide important insights into mechanisms of Prl-1 protection against olfactory CO2 stimulation induced brain disorder at the level of detailed neural circuits and functional molecular connections.

neuroscience

Using Optimal F-Measure and Random Resampling in Gene Ontology Enrichment Calculations

BackgroundA central question in bioinformatics is how to minimize arbitrariness and bias in analysis of patterns of enrichment in data. A prime example of such a question is enrichment of gene ontology (GO) classes in lists of genes. Our paper deals with two issues within this larger question. One is how to calculate the false discovery rate (FDR) within a set of apparently enriched ontologies, and the second how to set that FDR within the context of assessing significance for addressing biological questions, to answer these questions we compare a random resampling method with a commonly used method for assessing FDR, the Benjamini-Hochberg (BH) method. We further develop a heuristic method for evaluating Type II (false negative) errors to enable utilization of F-Measure binary classification theory for distinguishing \"significant\" from \"non-significant\" degrees of enrichment.\n\nResultsThe results show the preferability and feasibility of random resampling assessment of FDR over the analytical methods with which we compare it. They also show that the reasonableness of any arbitrary threshold depends strongly on the structure of the dataset being tested, suggesting that the less arbitrary method of F-measure optimization to determine significance threshold is preferable.\n\nConclusionTherefore, we suggest using F-measure optimization instead of placing an arbitrary threshold to evaluate the significance of Gene Ontology Enrichment results, and using resampling to replace analytical methods

bioinformatics