MAID : An effect size based model for microarray data integration across laboratories and platforms

<p>Abstract</p> <p>Background</p> <p>Gene expression profiling has the potential to unravel molecular mechanisms behind gene regulation and identify gene targets for therapeutic interventions. As microarray technology matures, the number of microarray studies has increased, resulting in many different datasets available for any given disease. The increase in sensitivity and reliability of measurements of gene expression changes can be improved through a systematic integration of different microarray datasets that address the same or similar biological questions.</p> <p>Results</p> <p>Traditional effect size models can not be used to integrate array data that directly compare treatment to control samples expressed as log ratios of gene expressions. Here we extend the traditional effect size model to integrate as many array datasets as possible. The extended effect size model (MAID) can integrate any array datatype generated with either single or two channel arrays using either direct or indirect designs across different laboratories and platforms. The model uses two standardized indices, the standard effect size score for experiments with two groups of data, and a new standardized index that measures the difference in gene expression between treatment and control groups for one sample data with replicate arrays. The statistical significance of treatment effect across studies for each gene is determined by appropriate permutation methods depending on the type of data integrated. We apply our method to three different expression datasets from two different laboratories generated using three different array platforms and two different experimental designs. Our results indicate that the proposed integration model produces an increase in statistical power for identifying differentially expressed genes when integrating data across experiments and when compared to other integration models. We also show that genes found to be significant using our data integration method are of direct biological relevance to the three experiments integrated.</p> <p>Conclusion</p> <p>High-throughput genomics data provide a rich and complex source of information that could play a key role in deciphering intricate molecular networks behind disease. Here we propose an extension of the traditional effect size model to allow the integration of as many array experiments as possible with the aim of increasing the statistical power for identifying differentially expressed genes.</p

Foreign investment in Scotland

A significant feature of the UK economy throughout the post-war period has been the growth in direct foreign investment in manufacturing industries. For the host nation the main benefits are employment creation, income generation and import reduction or export expansion. Scotland has been particularly successful in attracting the lion's inward investment for example in the period 1945- 1965 a total of 108,500 jobs were created by foreign firms setting up manufacturing units in the despite its size, obtained 46,221 (42.6%), whereas the second most SE England, gained only 16,926 (15.6%). The reasons for this success have been attributed primarily to a combination of the availability of labour in Scotland, the financial inducements offered by central government as part of regional policy and, the undoubted attraction of the environment, notably of course golf courses, for foreign businessmen. This brief paper explores the nature of Scotland's direct foreign investment and the reasons for its success

Review of the quarter's economic trends [April 1980]

This brief paper surveys recent world and UK economic data and reveals that there are some signs to suggest that the world economy will withstand the 1979 oil price shock better than it did in 1973/74. The main difference is that the 1979 price rise was not super-imposed on as severe an inflation as that which occurred on the previous occasion. The present rate of increase in the world prices should not reach the levels of the last cycle when the twelve month increase in manufacturing prices peaked at 23%. Advance warning by US economists that 1979 was going to be a year of difficulty did not go unnoticed by businessmen in that country who took steps in 1978 to avoid a repetition of the inventory boom and bust cycle which had proved so costly in the recession of 1973/74. Also, consumer expectations are adjusting towards a continuing rise in the price of oil. In the UK real GDP is expected to fall by 2½% from mid-year 1980. Thereafter, it is assumed to grow at an average annual rate of 1% for the next four years

The Scottish economy [October 1979]

The previous two issues of this Commentary have both indicated that the Scottish economy has been performing poorly since the mid 1970's. This is true in both an absolute and a relative sense. Manufacturing production only increased by 1.2% between 1976 and 1978 and, after dropping below 1975 levels in the first quarter of 1979, is unlikely to show any substantial improvement for the year as a whole. In an international context the 1975-1978 performance can best be described as appalling. Over the same period industrial production in Eire grew by 28%, in Japan and the US by 23% and in West Germany and France by 15%. Inertia in developing new markets and lack of competitiveness in existing markets both contributed substantially to the virtual stagnation of Scottish output. Because the problems are so diverse, so too must be the solutions

The tax and price index

A feature of this year's Budget was the shift in emphasis from direct taxation to indirect taxation. The annual yield of income tax has been reduced by £4½ billion while that of direct taxes was increased by a similar amount. It must be acknowledged that the new tax and price index has a number of deficiencies. It is only applicable to a proportion of the population, namely those who pay tax and whose gross income is less than £10,000 per annum. It takes no account of the social wage, nor of changes in benefits, such as the recent restructuring of child allowance. It smoothes out tax payments over a full year even though, for administrative reasons, these may fluctuate widely from month to month. This brief paper explores some of these deficiencies in more detail and assess their impact on taxation

The human male liver is predisposed to inflammation via enhanced myeloid responses to inflammatory triggers

BACKGROUND & AIM: Men have a higher prevalence of liver disease. Liver myeloid cells can regulate tissue inflammation, which drives progression of liver disease. We hypothesized that sex alters the responsiveness of liver myeloid cells, predisposing men to severe liver inflammation. METHODS: Luminex was done on plasma from Hepatitis B Virus infected patients undergoing nucleoside analogue cessation in 45 male and female patients. We collected immune cells from the sinusoids of uninfected livers of 53 male and female donors. Multiparametric flow cytometry was used to phenotype and characterize immune composition. Isolated monocytes were stimulated with TLR ligands to measure the inflammatory potential and the expression of regulators of TLR signaling. RESULTS: We confirmed that men experienced more frequent and severe liver damage upon Hepatitis B Virus reactivation, which was associated with inflammatory markers of myeloid activation. No differences were observed in the frequency or phenotype of sinusoidal myeloid cells between male and female livers. However, monocytes from male livers produced more inflammatory cytokines and chemokines in response to TLR stimulation than female monocytes. We investigated negative regulators of TLR signaling and found that TOLLIP was elevated in female liver-derived monocytes. CONCLUSIONS: Our data show that enhanced responsiveness of myeloid cells from the male liver predisposes men to inflammation, which was associated with altered expression of negative regulators of TLR signaling