Identification of Single- and Multiple-Class Specific Signature Genes from Gene Expression Profiles by Group Marker Index

Informative genes from microarray data can be used to construct prediction model and investigate biological mechanisms. Differentially expressed genes, the main targets of most gene selection methods, can be classified as single- and multiple-class specific signature genes. Here, we present a novel gene selection algorithm based on a Group Marker Index (GMI), which is intuitive, of low-computational complexity, and efficient in identification of both types of genes. Most gene selection methods identify only single-class specific signature genes and cannot identify multiple-class specific signature genes easily. Our algorithm can detect de novo certain conditions of multiple-class specificity of a gene and makes use of a novel non-parametric indicator to assess the discrimination ability between classes. Our method is effective even when the sample size is small as well as when the class sizes are significantly different. To compare the effectiveness and robustness we formulate an intuitive template-based method and use four well-known datasets. We demonstrate that our algorithm outperforms the template-based method in difficult cases with unbalanced distribution. Moreover, the multiple-class specific genes are good biomarkers and play important roles in biological pathways. Our literature survey supports that the proposed method identifies unique multiple-class specific marker genes (not reported earlier to be related to cancer) in the Central Nervous System data. It also discovers unique biomarkers indicating the intrinsic difference between subtypes of lung cancer. We also associate the pathway information with the multiple-class specific signature genes and cross-reference to published studies. We find that the identified genes participate in the pathways directly involved in cancer development in leukemia data. Our method gives a promising way to find genes that can involve in pathways of multiple diseases and hence opens up the possibility of using an existing drug on other diseases as well as designing a single drug for multiple diseases

Ca2+ store dynamics determines the pattern of activation of the store-operated Ca2+ current ICRAC in response to InsP3 in rat basophilic leukaemia cells

ICRAC and intracellular inositol 1,4,5-trisphosphate (InsP3) concentration is complex. In rat basophilic leukaemia (RBL-1) cells dialysed with high intracellular Ca2+ buffer, the relationship is supra-linear with a Hill coefficient of 12 and resembles an apparent ‘all-or-none’ phenomenon. The non-linearity seems to arise from InsP3 metabolism. However, it is not clear which InsP3-metabolising pathway engenders the non-linear behaviour nor whether ICRAC is always activated to its maximal extent by InsP3.Using the whole-cell patch clamp technique, we dialysed RBL-1 cells with different concentrations of the InsP3 analogue InsP3-F. InsP3-F is broken down by Ins(1,4,5)P3 5-phosphatase but is not a substrate for Ins(1,4,5)P3 3-kinase. The relationship between InsP3-F and ICRAC amplitude was supra-linear and very similar to that with InsP3 but was distinct from the graded relationship seen with the non-metabolisable analogue Ins2,4,5P3.In the presence of high intracellular Ca2+ buffer, InsP3-F activated ICRAC to its maximal extent. With moderate Ca2+ buffer, however, sub-maximal ICRAC could be obtained to a maximal InsP3-F concentration. Nevertheless, the relationship between the amplitude of ICRAC and InsP3-F concentration was still supra-linear.Submaximal ICRAC in response to InsP3-F in the presence of moderate Ca2+ buffer was due to partial depletion of the stores, because the size of the current could be increased by thapsigargin.The data suggest that first, Ins(1,4,5)P3 5-phosphatase is an important factor which contributes to the non-linear relationship between InsP3 concentration and the amplitude of ICRAC and second, InsP3 does not always activate ICRAC to its maximal extent. At moderate buffer strengths, submaximal ICRAC is evoked by maximal InsP3. However, the supra-linear relationship between InsP3 concentration and amplitude of the current still holds

Selenium status of healthy Turkish children

Selenium concentrations, in blood plasma, red blood cells, hair of 61 healthy children, ages 0-14 yr, were determined using hydride generation atomic absorption spectrometry Starting from late lactation period, selenium concentrations in all these matrices were found to be increasing with age. A good correlation was found between erythrocyte and plasma, hair and plasma, and hair and erythrocyte selenium concentrations. Although plasma, erythrocyte, and hair selenium concentrations of girls seemed to be higher than that of boys (only in erythrocytes), selenium concentrations of girls were found to be significantly (p < 0.002) higher than that of boys, 71 +/- 9 ng/mL, vs 65 +/- 10 ng/mL, respectively. Selenium status of Turkish children is found to be lower than that found in the literature; marginal selenium deficiency could be important in the development of some selenium deficiency related diseases. There is a need for extension of this study to healthy children from different regions in Turkey and to different disease states

The Effect of Ketogenic Diet on Serum Selenium Levels in Patients with Intractable Epilepsy

The aim of the present study was to evaluate serum selenium levels in children receiving olive oil-based ketogenic diet (KD) for intractable seizures for at least 1 year. Out of 320 patients who were initiated on KD, patients who continued receiving KD for at least 12 months were enrolled. Sixteen patients who had selenium deficiency at the time of starting KD were excluded. Finally, a total of 110 patients (mean age 7.3 +/- 4.2 years) were included. Serum selenium levels were measured at baseline and at 3, 6, and 12 months after treatment initiation by using atomic absorption spectroscopy. Selenium deficiency was defined as a serum selenium level < 48 mu g/L at each visit. Repeated measure ANOVA with post hoc Bonferroni correction was used for data analysis. Mean duration of KD was 15.3 +/- 4.3 months. Mean serum selenium levels were significantly lower at 6 and 12 months of KD treatment (66.2 +/- 23.3 and 57.2 +/- 16.2 mu g/L, respectively) compared to pre-treatment levels (79.3 +/- 25.7 mu g/L) (p = 0.001). On the other hand, selenium levels did not show any significant difference at 3 months of KD treatment (70.0 +/- 21.2 mu g/L) compared to baseline levels (p = 0.076). A total of 54 patients (49.1%) were diagnosed with selenium deficiency, and oral selenium medication was initiated for these patients. No relevant clinical findings were detected, and echocardiographic findings were normal in all patients. The decline of the serum selenium concentrations after 6 and 12 months of ketogenic diet suggests that patients on this highly prescriptive dietary treatment need close monitoring of this trace element