Oxidized low-density lipoproteins (oxLDL) and oxidized low-density lipoprotein autoantibodies (OLAB) have been detected in human plasma and atherosclerotic lesions. OLAB appear to play a role in the clearance of oxLDL from circulation. Higher levels of OLAB appear to be associated with a reduced risk of a wide range of cardiovascular diseases. We investigated the prognostic value of plasma oxLDL and OLAB in patients undergoing primary coronary balloon angioplasty for acute ST-elevation myocardial infarction (STEMI).
Plasma oxLDL and OLAB concentrations were measured in 56 patients with acute STEMI before primary angioplasty, and then 3 days, 7 days and 1 month after the acute event. Follow-up angiography was repeated 6 months later to detect the presence of restensosis (defined as >50% luminal diameter stenosis). The thrombolysis in myocardial infarction (TIMI) risk score was calculated to determine the relationship between OLAB/oxLDL ratio and TIMI risk scores.
Of the 56 patients, 18 (31%) had angiographic evidence of restenosis. Plasma OLAB concentrations were significantly lower in the restenosis group before angioplasty (181±114 vs. 335±257 U/L, p = 0.003), and at day 3 (155±92 vs. 277±185 U/L, p<0.001) and day 7 (177±110 vs. 352±279 U/L, p<0.001) after the acute event. There was no difference in oxLDL concentration between the two groups. The ratio of OLAB/oxLDL positively correlated with TIMI risk scores before angioplasty (p for trend analysis, p = 0.004), at day 3 (p = 0.008) and day 7 (p<0.001) after STEMI.
A relative deficit of OLAB, and hence likely impaired clearance of oxLDL, is associated with the risk of arterial restenosis after primary angioplasty for acute STEMI.
Gene set testing problem has become the focus of microarray data analysis. A gene set is a group of genes that are defined by a priori biological knowledge. Several statistical methods have been proposed to determine whether functional gene sets express differentially (enrichment and/or deletion) in variations of phenotypes. However, little attention has been given to analyzing the dependence structure among gene sets. In this study, we have proposed a novel statistical method of gene set association analysis to identify significantly associated gene sets using the coefficient of intrinsic dependence. The simulation studies show that the proposed method outperforms the conventional methods to detect general forms of association in terms of control of type I error and power. The correlation of intrinsic dependence has been applied to a breast cancer microarray dataset to quantify the un-supervised relationship between two sets of genes in the tumor and non-tumor samples. It was observed that the existence of gene-set association differed across various clinical cohorts. In addition, a supervised learning was employed to illustrate how gene sets, in signaling transduction pathways or subnetworks regulated by a set of transcription factors, can be discovered using microarray data. In conclusion, the coefficient of intrinsic dependence provides a powerful tool for detecting general types of association. Hence, it can be useful to associate gene sets using microarray expression data. Through connecting relevant gene sets, our approach has the potential to reveal underlying associations by drawing a statistically relevant network in a given population, and it can also be used to complement the conventional gene set analysis.
Cirrhotic patients with ascites are prone to develop various infectious diseases. This study aimed to evaluate the occurrence and effect of major infectious diseases on the mortality of cirrhotic patients with ascites.
We reviewed de-identified patient data from the National Health Insurance Database, derived from the Taiwan National Health Insurance Program, to enroll 4,576 cirrhotic patients with ascites, who were discharged from Taiwan hospitals between January 1, 2004 and June 30, 2004. We collected patients’ demographic and clinical data, and reviewed diagnostic codes to determine infectious diseases and comorbid disorders of their hospitalizations. Patients were divided into an infection group and non-infection group and hazard ratios (HR) were determined for specific infectious diseases.
Of the total 4,576 cirrhotic patients with ascites, 1,294 (28.2%) were diagnosed with infectious diseases during hospitalization. The major infectious diseases were spontaneous bacterial peritonitis (SBP) (645, 49.8%), urinary tract infection (151, 11.7%), and pneumonia (100, 7.7%). After adjusting for patients’ age, gender, and other comorbid disorders, the HRs of infectious diseases for 30-day and 90-day mortality of cirrhotic patients with ascites were 1.81 (1.54-2.11) and 1.60 (1.43-1.80) respectively, compared to those in the non-infection group. The adjusted HRs of pneumonia, urinary tract infection (UTI), spontaneous bacterial peritonitis (SBP), and sepsis without specific focus (SWSF) were 2.95 (2.05-4.25), 1.32 (0.86-2.05), 1.77 (1.45-2.17), and 2.19 (1.62-2.96) for 30-day mortality, and 2.57 (1.93-3.42), 1.36 (1.01-1.82), 1.51 (1.29-1.75), and 2.13 (1.70-2.66) for 90-day mortality, compared to those in the non-infection group.
Infectious diseases increased 30-day and 90-day mortality of cirrhotic patients with ascites. Among all infectious diseases identified, pneumonia carried the highest risk for mortality.
Cirrhosis; Ascites; Infections; Pneumonia; Spontaneous bacterial peritonitis
Cellulitis is a common infectious disease. However, the risk of cellulitis in cirrhotic patients is not well established, and whether liver cirrhosis is a risk factor for cellulitis remains unknown. This study evaluated the relationship between cellulitis and liver cirrhosis.
The National Health Insurance Database, which was derived from the Taiwan National Health Insurance program, was used to identify patients. The study group consisted of 39,966 patients with liver cirrhosis, and the comparison group consisted of 39,701 randomly selected age- and sex-matched patients.
During the 3-year follow-up period, 2,674 (6.7%) patients with liver cirrhosis developed cellulitis, and 1,587 (4.0%) patients without liver cirrhosis developed cellulitis (p<0.001). Following a Cox's regression analysis adjusted for age, sex, and underlying medical disorders, the cirrhotic patients demonstrated a greater risk for the occurrence of cellulitis than the non-cirrhotic patients during the 3-year period (hazard ratio [HR], 1.66; 95% confidence interval [CI], 1.55 to 1.77; p<0.001). Additionally, cirrhotic patients with complications also had a greater risk for the occurrence of cellulitis than those patients without complications (HR, 1.23; 95% CI, 1.14 to 1.33; p<0.001).
We conclude that cirrhotic patients have a greater risk of cellulitis than non-cirrhotic patients.
Cellulitis; Liver cirrhosis
The status of immunocompromised patients is well recognized in end stage renal disease (ESRD). As described recently, this acquired immune dysfunction in the uremic milieu may be one of the main pathogenic factors for mortality in ESRD. The aim of this study was to determine the relationship between the immune response following a hepatitis B vaccination (HBV vaccination) and the survival of maintenance dialysis patients.
A total of 156 patients (103 on hemodialysis and 53 on continuous ambulatory peritoneal dialysis) were recruited. After receiving a full dose of the HBV vaccination, all patients were followed up for to 5 years to evaluate the association of patient survival, cause of mortality, and immune response.
The response rate to the hepatitis B vaccination was 70.5%. There was no significant association between the immune response and the 5-year survival rate (p =0.600) or between the post-vaccination anti-HBs titers and the 5-year survival rate (p = 0.201). The logistic prediction model with the coefficient as non-response following HBV vaccination, diabetes mellitus, old age, and low albumin level could significantly predict infection-cause mortality (sensitivity = 0.842, specificity = 0.937).
There was no significant association between the immune response to HBV vaccination and the 5-year survival rate. However, non-response following HBV vaccination might be associated with infection-cause mortality in dialysis patients.
Hepatitis B vaccination; Immune response; Post-vaccination anti-HBs titers
The development of DNA microarray makes researchers screen thousands of genes simultaneously and it also helps determine high- and low-expression level genes in normal and disease tissues. Selecting relevant genes for cancer classification is an important issue. Most of the gene selection methods use univariate ranking criteria and arbitrarily choose a threshold to choose genes. However, the parameter setting may not be compatible to the selected classification algorithms. In this paper, we propose a new gene selection method (SVM-t) based on the use of t-statistics embedded in support vector machine. We compared the performance to two similar SVM-based methods: SVM recursive feature elimination (SVMRFE) and recursive support vector machine (RSVM). The three methods were compared based on extensive simulation experiments and analyses of two published microarray datasets. In the simulation experiments, we found that the proposed method is more robust in selecting informative genes than SVMRFE and RSVM and capable to attain good classification performance when the variations of informative and noninformative genes are different. In the analysis of two microarray datasets, the proposed method yields better performance in identifying fewer genes with good prediction accuracy, compared to SVMRFE and RSVM.
In 2010, an outbreak of coxsackievirus A6 (CA6) hand, foot and mouth disease (HFMD) occurred in Taiwan and some patients presented with onychomadesis and desquamation following HFMD. Therefore, we performed an epidemiological and molecular investigation to elucidate the characteristics of this outbreak.
Patients who had HFMD with positive enterovirus isolation results were enrolled. We performed a telephone interview with enrolled patients or their caregivers to collect information concerning symptoms, treatments, the presence of desquamation, and the presence of nail abnormalities. The serotypes of the enterovirus isolates were determined using indirect immunofluorescence assays. The VP1 gene was sequenced and the phylogenetic tree for the current CA6 strains in 2010, 52 previous CA6 strains isolated in Taiwan from 1998 through 2009, along with 8 reference sequences from other countries was constructed using the neighbor-joining command in MEGA software.
Of the 130 patients with laboratory-confirmed CA6 infection, some patients with CA6 infection also had eruptions around the perioral area (28, 22%), the trunk and/or the neck (39, 30%) and generalized skin eruptions (6, 5%) in addition to the typical presentation of skin eruptions on the hands, feet, and mouths. Sixty-six (51%) CA6 patients experienced desquamation of palms and soles after the infection episode and 48 (37%) CA6 patients developed onychomadesis, which only occurred in 7 (5%) of 145 cases with non-CA6 enterovirus infection (p < 0.001). The sequences of viral protein 1 of CA6 in 2010 differ from those found in Taiwan before 2010, but are similar to those found in patients in Finland in 2008.
HFMD patients with CA6 infection experienced symptoms targeting a broader spectrum of skin sites and more profound tissue destruction, i.e., desquamation and nail abnormalities.
Coxsackievirus A6; Hand; foot; and mouth disease; Onychomadesis
This study aimed to compare the clinical presentations of Aeromonas hydrophila, A. veronii biovar sobria and A. caviae monomicrobial bacteremia by a retrospective method at three hospitals in Taiwan during an 8-yr period. There were 87 patients with A. hydrophila bacteremia, 45 with A. veronii biovar sobria bacteremia and 22 with A. caviae bacteremia. Compared with A. hydrophila and A. veronii biovar sobria bacteremia, A. caviae bacteremia was more healthcare-associated (45 vs 30 and 16%; P = 0.031). The patients with A. caviae bacteremias were less likely to have liver cirrhosis (27 vs 62 and 64%; P = 0.007) and severe complications such as shock (9 vs 40 and 47%; P = 0.009) and thrombocytopenia (45 vs 67 and 87%; P = 0.002). The APACHE II score was the most important risk factor of Aeromonas bacteremia-associated mortalities. The APACHE II scores of A. caviae bacteremias were lower than A. hydrophila bacteremia and A. veronii biovar sobria bacteremia (7 vs 14 and 16 points; P = 0.002). In conclusion, the clinical presentation of A. caviae bacteremia was much different from A. hydrophila and A. veronii biovar sobria bacteremia. The severity and mortality of A. caviae bacteremia were lower than A. hydrophila or A. veronii biovar sobria bacteremia.
Aeromonas hydrophilia; Aeromonas veronii biovar sobria; Aeromonas caviae; Bacteremia
Iron-inducible transcription of the ap65-1 gene in Trichomonas vaginalis involves at least three Myb-like transcriptional factors (tvMyb1, tvMyb2 and tvMyb3) that differentially bind to two closely spaced promoter sites, MRE-1/MRE-2r and MRE-2f. Here, we defined a fragment of tvMyb2 comprising residues 40–156 (tvMyb240–156) as the minimum structural unit that retains near full binding affinity with the promoter DNAs. Like c-Myb in vertebrates, the DNA-free tvMyb240–156 has a flexible and open conformation. Upon binding to the promoter DNA elements, tvMyb240–156 undergoes significant conformational re-arrangement and structure stabilization. Crystal structures of tvMyb240–156 in complex with promoter element-containing DNA oligomers showed that 5′-a/gACGAT-3′ is the specific base sequence recognized by tvMyb240–156, which does not fully conform to that of the Myb binding site sequence. Furthermore, Lys49, which is upstream of the R2 motif (amino acids 52–102) also participates in specific DNA sequence recognition. Intriguingly, tvMyb240–156 binds to the promoter elements in an orientation opposite to that proposed in the HADDOCK model of the tvMyb135–141/MRE-1-MRE-2r complex. These results shed new light on understanding the molecular mechanism of Myb–DNA recognition and provide a framework to study the molecular basis of transcriptional regulation of myriad Mybs in T. vaginalis.
In a previous 52-week trial, treatment with alglucosidase alfa markedly improved cardiomyopathy, ventilatory function, and overall survival among 18 children <7 months old with infantile-onset Pompe disease. Sixteen of the 18 patients enrolled in an extension study, where they continued to receive alglucosidase alfa at either 20 mg/kg biweekly (n=8) or 40 mg/kg biweekly (n=8), for up to a total of 3 years. These children continued to exhibit the benefits of alglucosidase alfa at the age of 36 months. Cox regression analyses showed that over the entire study period, alglucosidase alfa treatment reduced the risk of death by 95%, reduced the risk of invasive ventilation or death by 91%, and reduced the risk of any type of ventilation or death by 87%, as compared to an untreated historical control group. Cardiomyopathy continued to improve and 11 patients learned and sustained substantial motor skills. No significant differences in either safety or efficacy parameters were observed between the 20 mg/kg and 40 mg/kg biweekly doses. Overall, long-term alglucosidase alfa treatment markedly extended survival as well as ventilation-free survival, and improved cardiomyopathy.
Delayed diagnosis of scabies can cause an institutional outbreak, which causes considerably economic burden to control. This study was to find the risk factors for delayed diagnosis of scabies in hospitalized patients from long-term care facilities.
We conducted a retrospective analysis of the hospitalized patients from long-term care facilities, diagnosed to have scabies between January 2006 and December 2008. A stepwise logistic regression analysis was performed to determine the risk factors for delayed diagnosis of scabies.
A total of 706 episodes with scabies were identified retrospectively in 399 hospitalized patients from long-term care facilities. Of these, 44 episodes were considered as delayed diagnosis of scabies. These patients were more associated with chronic usage of steroid (73% vs. 10%, P < 0.001) and had longer duration of hospitalization than the others (30 vs. 13 days, P < 0.001). After logistic regression, steroid therapy was the risk factor of delayed diagnosis of scabies (odds ratio: 23.493).
In the patients from long-term care facilities, clinical physicians should pay more attention to those with chronic usage of steroid to avoid delayed diagnosis of scabies.
Scabies; Delayed diagnosis; Risk factor; Long-term care facility
Relying on surveillance of clinical cases limits the ability to understand the full impact and severity of an epidemic, especially when subclinical cases are more likely to be present in the early stages. Little is known of the infection and transmissibility of the 2009 H1N1 pandemic influenza (pH1N1) virus outside of Mexico prior to clinical cases being reported, and of the knowledge pertaining to immunity and incidence of infection during April–June, which is essential for understanding the nature of viral transmissibility as well as for planning surveillance and intervention of future pandemics.
Starting in the fall of 2008, 306 persons from households with schoolchildren in central Taiwan were followed sequentially and serum samples were taken in three sampling periods for haemagglutination inhibition (HI) assay. Age-specific incidence rates were calculated based on seroconversion of antibodies to the pH1N1 virus with an HI titre of 1∶40 or more during two periods: April–June and September–October in 2009. The earliest time period with HI titer greater than 40, as well as a four-fold increase of the neutralization titer, was during April 26–May 3. The incidence rates during the pre-epidemic phase (April–June) and the first wave (July–October) of the pandemic were 14.1% and 29.7%, respectively. The transmissibility of the pH1N1 virus during the early phase of the epidemic, as measured by the effective reproductive number R0, was 1.16 (95% confidence interval (CI): 0.98–1.34).
Approximately one in every ten persons was infected with the 2009 pH1N1 virus during the pre-epidemic phase in April–June. The lack of age-pattern in seropositivity is unexpected, perhaps highlighting the importance of children as asymptomatic transmitters of influenza in households. Although without virological confirmation, our data raise the question of whether there was substantial pH1N1 transmission in Taiwan before June, when clinical cases were first detected by the surveillance network.
The molecular heterogeneity of human tumors challenges the development of effective preventive and therapeutic strategies. To overcome this issue, a rational approach is the concomitant targeting of clinically relevant cellular abnormalities with combination therapy or a potent multi-targeted agent. OSU-A9 is a novel indole-3-carbinol derivative that retains the parent compound's ability to perturb multiple components of oncogenic signaling, but provides marked advantages in chemical stability and antitumor potency. Here, we show that OSU-A9 exhibits two orders of magnitude greater potency than indole-3-carbinol in inducing apoptosis in various breast cancer cell lines with distinct genetic abnormalities, including MCF-7, MDA-MB-231 and SKBR3, with the half maximal inhibitory concentration in the range of 1.2–1.8 μM vis-à-vis 200 μM for indole-3-carbinol. This differential potency was paralleled by OSU-A9’s superior activity against multiple components of the Akt–nuclear factor-kappa B (NF-κB) and stress response signaling pathways. Notable among these were the increased estrogen receptor (ER)-β/ERα expression ratio, reduced expression of HER2 and CXCR4 and the upregulation of aryl hydrocarbon receptor expression and its downstream target NF-E2 p45-regulated factor (Nrf2). Non-malignant MCF-10A cells were resistant to OSU-A9’s antiproliferative effects. Daily oral administration of OSU-A9 at 25 and 50 mg/kg for 49 days significantly inhibited MCF-7 tumor growth by 59 and 70%, respectively, without overt signs of toxicity or evidence of induced hepatic biotransformation enzymes. In summary, OSU-A9 is a potent, orally bioavailable inhibitor of the Akt–NF-κB signaling network, targeting multiple aspects of breast tumor pathogenesis and progression. Thus, its translational potential for the treatment or prevention of breast cancer warrants further investigation.
In the title molecule, C14H13N3O, the dihedral angle between the mean planes of the benzotriazole ring system and the benzene ring is 57.8 (2)°.
In the title compound, [Pd(C17H13N2O)2], the PdII atom is tetracoordinated by two N atoms and two O atoms from two bidentate methylphenyldiazenylnaphtolate ligands, forming a square-planar complex. The two N atoms and two O atoms around the PdII atom are trans to each other (as the PdII atom lies on a crystallographic inversion centre) with O—Pd—N bond angles of 89.60 (11) and 90.40 (11)°. The distances between the PdII atom and the coordinated O and N atoms are 1.966 (3) and 2.009 (3) Å, respectively.
In the title compound, C14H11N3O2, the dihedral angle between the mean planes of the benzotriazole ring system and the benzene ring of the salicylaldehyde group is 2.4 (2)°. There is an intramolecular O—H⋯N hydrogen bond which may influence the molecular conformation.
During the course of oncogenesis and tumor progression, cancer cells constitutively upregulate signaling pathways relevant to cell proliferation and survival as a strategy to overcome genomic instability and acquire resistance phenotype to chemotherapeutic agents. In light of this clinical and molecular heterogeneity of human cancers, it is desirable to concomitantly target these genetic abnormalities by using an agent with pleiotropic mode of action. Indole-3-carbinol and its metabolite 3,3’-diindoylmethane (DIM) target multiple aspects of cancer cell cycle regulation and survival including Akt-NFκB signaling, caspase activation, cyclin-dependent kinase activities, estrogen metabolism, estrogen receptor signaling, endoplasmic reticulum stress, and BRCA gene expression. This broad spectrum of antitumor activities in conjunction with low toxicity underscores the translational value of indole-3-carbinol and its metabolites in cancer prevention/therapy. Furthermore, novel antitumor agents with overlapping underlying mechanisms have emerged via structural optimization of indole-3-carbinol and DIM, which may provide considerable therapeutic advantages over the parental compounds with respect to chemical stability and anti-tumor potency. Together, these agents might foster new strategies for cancer prevention and therapy.
indole-3-carbinol; 3,3’-diindoylmethane; Akt-NFκB signaling; nuclear receptor signaling; endoplasmic reticulum stress; BRCA gene expression
In the title complex, [Pd(C13H10N3O)2], the PdII atom is tetracoordinated by two N atoms and two O atoms from two bidentate 2-(2H-benzotriazol-2-yl)-4-methylphenolate ligands, forming a square-planar environment. The asymmetric unit contains one half molecule in which the Pd atom lies on a centre of symmetry.
ARL4D is a developmentally regulated member of the ADP-ribosylation factor/ARF-like protein (ARF/ARL) family of Ras-related GTPases. Although the primary structure of ARL4D is very similar to that of other ARF/ARL molecules, its function remains unclear. Cytohesin-2/ARF nucleotide-binding-site opener (ARNO) is a guanine nucleotide-exchange factor (GEF) for ARF, and, at the plasma membrane, it can activate ARF6 to regulate actin reorganization and membrane ruffling. We show here that ARL4D interacts with the C-terminal pleckstrin homology (PH) and polybasic c domains of cytohesin-2/ARNO in a GTP-dependent manner. Localization of ARL4D at the plasma membrane is GTP- and N-terminal myristoylation-dependent. ARL4D(Q80L), a putative active form of ARL4D, induced accumulation of cytohesin-2/ARNO at the plasma membrane. Consistent with a known action of cytohesin-2/ARNO, ARL4D(Q80L) increased GTP-bound ARF6 and induced disassembly of actin stress fibers. Expression of inactive cytohesin-2/ARNO(E156K) or small interfering RNA knockdown of cytohesin-2/ARNO blocked ARL4D-mediated disassembly of actin stress fibers. Similar to the results with cytohesin-2/ARNO or ARF6, reduction of ARL4D suppressed cell migration activity. Furthermore, ARL4D-induced translocation of cytohesin-2/ARNO did not require phosphoinositide 3-kinase activation. Together, these data demonstrate that ARL4D acts as a novel upstream regulator of cytohesin-2/ARNO to promote ARF6 activation and modulate actin remodeling.
Many researchers are concerned with the comparability and reliability of microarray gene expression data. Recent completion of the MicroArray Quality Control (MAQC) project provides a unique opportunity to assess reproducibility across multiple sites and the comparability across multiple platforms. The MAQC analysis presented for the conclusion of inter- and intra-platform comparability/reproducibility of microarray gene expression measurements is inadequate. We evaluate the reproducibility/comparability of the MAQC data for 12901 common genes in four titration samples generated from five high-density one-color microarray platforms and the TaqMan technology. We discuss some of the problems with the use of correlation coefficient as metric to evaluate the inter- and intra-platform reproducibility and the percent of overlapping genes (POG) as a measure for evaluation of a gene selection procedure by MAQC.
A total of 293 arrays were used in the intra- and inter-platform analysis. A hierarchical cluster analysis shows distinct differences in the measured intensities among the five platforms. A number of genes show a small fold-change in one platform and a large fold-change in another platform, even though the correlations between platforms are high. An analysis of variance shows thirty percent of gene expressions of the samples show inconsistent patterns across the five platforms. We illustrated that POG does not reflect the accuracy of a selected gene list. A non-overlapping gene can be truly differentially expressed with a stringent cut, and an overlapping gene can be non-differentially expressed with non-stringent cutoff. In addition, POG is an unusable selection criterion. POG can increase or decrease irregularly as cutoff changes; there is no criterion to determine a cutoff so that POG is optimized.
Using various statistical methods we demonstrate that there are differences in the intensities measured by different platforms and different sites within platform. Within each platform, the patterns of expression are generally consistent, but there is site-by-site variability. Evaluation of data analysis methods for use in regulatory decision should take no treatment effect into consideration, when there is no treatment effect, "a fold-change cutoff with a non-stringent p-value cutoff" could result in 100% false positive error selection.
A microarray study may select different differentially expressed gene sets because of different selection criteria. For example, the fold-change and p-value are two commonly known criteria to select differentially expressed genes under two experimental conditions. These two selection criteria often result in incompatible selected gene sets. Also, in a two-factor, say, treatment by time experiment, the investigator may be interested in one gene list that responds to both treatment and time effects.
We propose three layer ranking algorithms, point-admissible, line-admissible (convex), and Pareto, to provide a preference gene list from multiple gene lists generated by different ranking criteria. Using the public colon data as an example, the layer ranking algorithms are applied to the three univariate ranking criteria, fold-change, p-value, and frequency of selections by the SVM-RFE classifier. A simulation experiment shows that for experiments with small or moderate sample sizes (less than 20 per group) and detecting a 4-fold change or less, the two-dimensional (p-value and fold-change) convex layer ranking selects differentially expressed genes with generally lower FDR and higher power than the standard p-value ranking. Three applications are presented. The first application illustrates a use of the layer rankings to potentially improve predictive accuracy. The second application illustrates an application to a two-factor experiment involving two dose levels and two time points. The layer rankings are applied to selecting differentially expressed genes relating to the dose and time effects. In the third application, the layer rankings are applied to a benchmark data set consisting of three dilution concentrations to provide a ranking system from a long list of differentially expressed genes generated from the three dilution concentrations.
The layer ranking algorithms are useful to help investigators in selecting the most promising genes from multiple gene lists generated by different filter, normalization, or analysis methods for various objectives.
This paper compares the type I error and power of the one- and two-sample t-tests, and the one- and two-sample permutation tests for detecting differences in gene expression between two microarray samples with replicates using Monte Carlo simulations. When data are generated from a normal distribution, type I errors and powers of the one-sample parametric t-test and one-sample permutation test are very close, as are the two-sample t-test and two-sample permutation test, provided that the number of replicates is adequate. When data are generated from a t-distribution, the permutation tests outperform the corresponding parametric tests if the number of replicates is at least five. For data from a two-color dye swap experiment, the one-sample test appears to perform better than the two-sample test since expression measurements for control and treatment samples from the same spot are correlated. For data from independent samples, such as the one-channel array or two-channel array experiment using reference design, the two-sample t-tests appear more powerful than the one-sample t-tests.