Evaluating methods for ranking differentially expressed genes applied to microArray quality control data

<p>Abstract</p> <p>Background</p> <p>Statistical methods for ranking differentially expressed genes (DEGs) from gene expression data should be evaluated with regard to high sensitivity, specificity, and reproducibility. In our previous studies, we evaluated eight gene ranking methods applied to only Affymetrix GeneChip data. A more general evaluation that also includes other microarray platforms, such as the Agilent or Illumina systems, is desirable for determining which methods are suitable for each platform and which method has better inter-platform reproducibility.</p> <p>Results</p> <p>We compared the eight gene ranking methods using the MicroArray Quality Control (MAQC) datasets produced by five manufacturers: Affymetrix, Applied Biosystems, Agilent, GE Healthcare, and Illumina. The area under the curve (AUC) was used as a measure for both sensitivity and specificity. Although the highest AUC values can vary with the definition of "true" DEGs, the best methods were, in most cases, either the weighted average difference (WAD), rank products (RP), or intensity-based moderated <it>t </it>statistic (ibmT). The percentages of overlapping genes (POGs) across different test sites were mainly evaluated as a measure for both intra- and inter-platform reproducibility. The POG values for WAD were the highest overall, irrespective of the choice of microarray platform. The high intra- and inter-platform reproducibility of WAD was also observed at a higher biological function level.</p> <p>Conclusion</p> <p>These results for the five microarray platforms were consistent with our previous ones based on 36 real experimental datasets measured using the Affymetrix platform. Thus, recommendations made using the MAQC benchmark data might be universally applicable.</p

Ranking differentially expressed genes from Affymetrix gene expression data: methods with reproducibility, sensitivity, and specificity

<p>Abstract</p> <p>Background</p> <p>To identify differentially expressed genes (DEGs) from microarray data, users of the Affymetrix GeneChip system need to select both a preprocessing algorithm to obtain expression-level measurements and a way of ranking genes to obtain the most plausible candidates. We recently recommended suitable combinations of a preprocessing algorithm and gene ranking method that can be used to identify DEGs with a higher level of sensitivity and specificity. However, in addition to these recommendations, researchers also want to know which combinations enhance reproducibility.</p> <p>Results</p> <p>We compared eight conventional methods for ranking genes: weighted average difference (WAD), average difference (AD), fold change (FC), rank products (RP), moderated <it>t </it>statistic (modT), significance analysis of microarrays (samT), shrinkage <it>t </it>statistic (shrinkT), and intensity-based moderated <it>t </it>statistic (ibmT) with six preprocessing algorithms (PLIER, VSN, FARMS, multi-mgMOS (mmgMOS), MBEI, and GCRMA). A total of 36 real experimental datasets was evaluated on the basis of the area under the receiver operating characteristic curve (AUC) as a measure for both sensitivity and specificity. We found that the RP method performed well for VSN-, FARMS-, MBEI-, and GCRMA-preprocessed data, and the WAD method performed well for mmgMOS-preprocessed data. Our analysis of the MicroArray Quality Control (MAQC) project's datasets showed that the FC-based gene ranking methods (WAD, AD, FC, and RP) had a higher level of reproducibility: The percentages of overlapping genes (POGs) across different sites for the FC-based methods were higher overall than those for the <it>t</it>-statistic-based methods (modT, samT, shrinkT, and ibmT). In particular, POG values for WAD were the highest overall among the FC-based methods irrespective of the choice of preprocessing algorithm.</p> <p>Conclusion</p> <p>Our results demonstrate that to increase sensitivity, specificity, and reproducibility in microarray analyses, we need to select suitable combinations of preprocessing algorithms and gene ranking methods. We recommend the use of FC-based methods, in particular RP or WAD.</p

Impact of single nucleotide polymorphism on short stature and reduced tongue pressure among community-dwelling elderly Japanese participants: a cross-sectional study

Background: Asian-specific single nucleotide polymorphism (SNPs) (rs3782886) is reported to be associated with myocardial infarction; sarcopenia is reported to be associated with coronary subclinical atherosclerosis. On the other hand, short stature has been revealed as an independent risk factor for cardiovascular disease. However, no studies have reported on the association between sarcopenia and short stature nor on the impact of rs3782886 on this association. Methods: Since reduced maximum voluntary tongue pressure against the palate (MTP) reflects one aspect of sarcopenia, we conducted a cross-sectional study of 537 community-dwelling elderly Japanese participants aged 60?89 years who had participated in a general health checkup in 2015. Short stature was defined as values at or under the 25th percentile, and reduced MTP was defined as the lowest tertile of the study population (<158.0 cm and <26.5 kPa for men, <145.0 cm and <24.1 kPa for women). Results: Independent of classical cardiovascular risk factors, short stature was revealed to be positively associated with reduced MTP. The adjusted-odds ratio (OR) and 95% confidence interval (CI) of reduced MTP for short stature was 1.87 (1.19, 2.94). We also found that independent of known cardiovascular risk factors, with the non-minor homo of rs3782886 taken as the reference group, the adjusted OR and 95% CI for short stature and reduced MTP of the minor homo allele were 3.06 (1.23, 7.63) and 3.26 (1.33, 8.03), respectively. Conclusion: Short stature is independently associated with reduced MTP, with Asian-specific SNPs possibly playing an important role in this association

Triglycerides and blood pressure in relation to circulating CD34-positive cell levels among community-dwelling elderly Japanese men: a cross-sectional study

Background: Triglycerides are reported to be positively associated with blood pressure (both systolic and diastolic). However, in a previous study, we reported a significant positive association between triglycerides and circulating CD34-positive cells (endothelial repair) among non-hypertensive, but not hypertensive, participants. Since hypertension and endothelial dysfunction have a bi-directional association (vicious cycle), the status of circulating CD34-positive cells may influence the association between triglycerides and hypertension. Methods: Since antihypertensive medication use may influence results of the present study, we conducted a cross-sectional study of 327 community dwelling elderly (aged 60-69 years) Japanese participants who were not taking anti-hypertensive medication and who had participated in a general health check-up in 2013-2015. Results: Participants were classified into two groups based on median values of circulating CD34-positive cells (0.93 cells/μL). For participants with lower circulating CD34-positive cells (n = 165), a significant positive association was seen between triglycerides and blood pressure, but not for participants with higher circulating CD34-positive cells (n = 162). The multivariable standardized parameter estimates (β) and p values of systolic blood pressure and diastolic blood pressure were 0.23 (p = 0.007) and 0.18 (p = 0.036) for participants with lower circulating CD34-positive cells and 0.08 (p = 0.409) and 0.03 (p = 0.786) for those with higher circulating CD34-positive cells. Conclusion: A significant positive association between triglycerides and blood pressure exists among those with lower, but not higher, circulating CD34-positive cells. The level of circulating CD34-positive cells acts as a determinant factor for the association between triglycerides and blood pressure

A short sequence for the iterative synthesis of fused polyethers

A simple and efficient four‐step sequence for the synthesis of fused polyether arrays has been developed. Cyclic ethers are installed by sequential alkynyl ether formation, carbocupration, ring‐closing metathesis and hydroboration with acidic workup. Crucially, the alkene required for the subsequent ring formation by ring‐closing metathesis is present in the substrate but is masked in the form of a vinylic silane, which prevents competitive metathesis of the side chain. Generation of the reactive alkene from the unreactive vinylic silane is accomplished by hydroboration and subsequent acid‐mediated Peterson elimination of the intermediate hydroxysilane

Association between alkaline phosphatase and hypertension in a rural Japanese population: The Nagasaki Islands study

Background: Although serum alkaline phosphatase (ALP) levels have been associated with hypertension, and ALP is known as an enzyme affected by alcohol consumption, no study has been published on the associations between ALP and the risk of hypertension in relation to drinking status.Methods: We conducted a cross-sectional study of 2,681 participants (837 men and 1,846 women) aged 30 to 89 years undergoing a general health check-up to investigate the associations between ALP and hypertension in relation to drinking status.Results: Of the 2,681 participants, 1,549 (514 men and 1,035 women) were diagnosed with hypertension. A sex difference was observed for the relationship between ALP and hypertension. While no significant association was observed for men, the association was significantly positive for women. The multivariable adjusted odds ratio and 95% coincidence interval (CI) of hypertension per increment of 1-log ALP were 0.95 (95% CI: 0.56 to 1.59) for men and 1.57 (95% CI: 1.07 to 2.33) for women. When this analysis was restricted to nondrinkers, a significantly elevated risk of hypertension was observed for men and remained significant for women; that is, 3.32 (95% CI: 1.38 to 8.02) for men and 1.68 (95% CI: 1.11 to 2.55) for women.Conclusion: ALP is associated with hypertension for both male and female nondrinkers, but not for drinkers. For analyses of associations between ALP and blood pressure, alcohol consumption should thus be considered a potential confounder