Bayesian testing of many hypotheses ×\times many genes: A study of sleep apnea

Substantial statistical research has recently been devoted to the analysis of large-scale microarray experiments which provide a measure of the simultaneous expression of thousands of genes in a particular condition. A typical goal is the comparison of gene expression between two conditions (e.g., diseased vs. nondiseased) to detect genes which show differential expression. Classical hypothesis testing procedures have been applied to this problem and more recent work has employed sophisticated models that allow for the sharing of information across genes. However, many recent gene expression studies have an experimental design with several conditions that requires an even more involved hypothesis testing approach. In this paper, we use a hierarchical Bayesian model to address the situation where there are many hypotheses that must be simultaneously tested for each gene. In addition to having many hypotheses within each gene, our analysis also addresses the more typical multiple comparison issue of testing many genes simultaneously. We illustrate our approach with an application to a study of genes involved in obstructive sleep apnea in humans.Comment: Published in at http://dx.doi.org/10.1214/09-AOAS241 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Bayesian testing of many hypothesis x many genes: a study of sleep apnea

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldSubstantial statistical research has recently been devoted to the analysis of large-scale microarray experiments which provide a measure of the simultaneous expression of thousands of genes in a particular condition. A typical goal is the comparison of gene expression between two conditions (eg. diseased vs. non-diseased) to detect genes which show differential expression. Classical hypothesis testing procedures have been applied to this problem and more recent work has employed sophisticated models that allow for the sharing of information across genes.However,many recent gene expression studies have an experimental design with several conditions that requires an even more involved hypothesis testing approach. In this paper, we use a hierarchical Bayesian model to address the situation where there are many hypotheses that must be simultaneously tested for each gene. In addition to having many hypotheses within each gene, our analysis also addresses the more typical multiple comparison issue of testing many genes simultaneously. We illustrate our approach with an application to a study of genes involved in obstructive sleep apnea in humans

The design of RIP belts impacts the reliability and quality of the measured respiratory signals.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadPurpose: Evaluate the effect of respiratory inductance plethysmography (RIP) belt design on the reliability and quality of respiratory signals. A comparison of cannula flow to disposable cut-to-fit, semi-disposable folding and disposable RIP belts was performed in clinical home sleep apnea testing (HSAT) studies. Methods: This was a retrospective study using clinical HSAT studies. The signal reliability of cannula, thorax, and abdomen RIP belts was determined by automatically identifying periods during which the signals did not represent respiratory airflow and breathing movements. Results were verified by manual scoring. RIP flow quality was determined by examining the correlation between the RIP flow and cannula flow when both signals were considered reliable. Results: Of 767 clinical HSAT studies, mean signal reliability of the cut-to-fit, semi-disposable, and disposable thorax RIP belts was 83.0 ± 26.2%, 76.1 ± 24.4%, and 98.5 ± 9.3%, respectively. The signal reliability of the cannula was 92.5 ± 16.1%, 87.0 ± 23.3%, and 85.5 ± 24.5%, respectively. The automatic assessment of signal reliability for the RIP belts and cannula flow had a sensitivity of 50% and a specificity of 99% compared with manual assessment. The mean correlation of cannula flow to RIP flow from the cut-to-fit, semi-disposable, and disposable RIP belts was 0.79 ± 0.24, 0.52 ± 0.20, and 0.86 ± 0.18, respectively. Conclusion: The design of RIP belts affects the reliability and quality of respiratory signals. The disposable RIP belts that had integrated contacts and did not fold on top of themselves performed the best. The cut-to-fit RIP belts were most likely to be unreliable, and the semi-disposable folding belts produced the lowest-quality RIP flow signals compared to the cannula flow signal. Keywords: Obstructive sleep apnea (OSA); Respiratory airflow; Respiratory inductance plethysmography (RIP) belts; Signal quality; Signal reliability.Icelandic Research Fund Horizon 2020 grant (H2020-SMEINST-2-2016-2017

Single slice vs. volumetric MR assessment of visceral adipose tissue: reliability and validity among the overweight and obese.

To access publisher's full text version of this article. Please click on the hyperlink in Additional Links field.Visceral adipose tissue (VAT) is associated with abnormal cardiovascular and metabolic profiles. Total VAT volume of the abdominal compartment by magnetic resonance imaging (MRI) is the gold-standard measurement for VAT but is costly and time consuming. Prior studies suggest VAT area on a single slice MR image may serve as a surrogate for total VAT volume but it is unknown if this relationship is maintained in overweight and obese men and women. Untreated sleep apnea subjects enrolled into the Icelandic Sleep Apnea Cohort (ISAC) underwent abdominal MRI. VAT area and subcutaneous adipose tissue (SAT) area at the L2-L3 and L4-L5 interspaces and total VAT and SAT volumes were determined by manual examination using image analysis software; 539 men and 129 women with mean ages of 54.1 and 58.8 years and mean BMI of 32.2 kg/m(2) and 33.7 kg/m(2), respectively, were studied. Mean total VAT volume was 40% smaller and mean total SAT was 25% larger among females compared with males. The correlation with VAT volume was significantly larger for L2-L3 VAT area (r = 0.96) compared to L4-L5 VAT area (r = 0.83). The difference in correlation coefficients was statistically significant (nonparametric bootstrap P < 0.001 with 95% confidence interval (CI) for the difference from 0.11 to 0.15. VAT area at L2-L3 was also significantly better correlated with VAT volume than traditional anthropometric variables. Linear regression analyses demonstrated that L2-L3 area alone was sufficient for predicting total VAT volume and that the nature of the linear association was maintained across all levels of obesity and in both genders.NIH HL070267 HL09430

Increased nocturnal arterial pulsation frequencies of obstructive sleep apnoea patients is associated with an increased number of lapses in a psychomotor vigilance task.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadObjectives: Besides hypoxaemia severity, heart rate variability has been linked to cognitive decline in obstructive sleep apnoea (OSA) patients. Thus, our aim was to examine whether the frequency domain features of a nocturnal photoplethysmogram (PPG) can be linked to poor performance in the psychomotor vigilance task (PVT). Methods: PPG signals from 567 suspected OSA patients, extracted from Type 1 diagnostic polysomnography, and corresponding results of PVT were retrospectively examined. The frequency content of complete PPGs was determined, and analyses were conducted separately for men (n=327) and women (n=240). Patients were grouped into PVT performance quartiles based on the number of lapses (reaction times ≥500 ms) and within-test variation in reaction times. The best-performing (Q1) and worst-performing (Q4) quartiles were compared due the lack of clinical thresholds in PVT. Results: We found that the increase in arterial pulsation frequency (APF) in both men and women was associated with a higher number of lapses. Higher APF was also associated with higher within-test variation in men, but not in women. Median APF (β=0.27, p=0.01), time spent under 90% saturation (β=0.05, p<0.01), female sex (β=1.29, p<0.01), older age (β=0.03, p<0.01) and subjective sleepiness (β=0.07, p<0.01) were significant predictors of belonging to Q4 based on lapses. Only female sex (β=0.75, p<0.01) and depression (β=0.91, p<0.02) were significant predictors of belonging to Q4 based on the within-test variation. Conclusions: In conclusion, increased APF in PPG provides a possible polysomnography indicator for deteriorated vigilance especially in male OSA patients. This finding highlights the connection between cardiorespiratory regulation, vigilance and OSA. However, our results indicate substantial sex-dependent differences that warrant further prospective studies.Research Committee of the Kuopio University Hospital Catchment Area for the State Research Funding Academy of Finland Seinajoki Central Hospital Competitive State Research Financing of Expert Responsibility Area of Tampere University Hospital VTR3242 Business Finland Paulo Foundation Paivikki & Sakari Sohlberg Foundation Research Foundation of the Pulmonary Diseases Finnish Cultural Foundation Alfred Kordelin Foundation Tampere Tuberculosis Foundation Respiratory Foundation of Kuopio Regio

Bayesian testing of many hypothesis x many genes: a study of sleep apnea

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldSubstantial statistical research has recently been devoted to the analysis of large-scale microarray experiments which provide a measure of the simultaneous expression of thousands of genes in a particular condition. A typical goal is the comparison of gene expression between two conditions (eg. diseased vs. non-diseased) to detect genes which show differential expression. Classical hypothesis testing procedures have been applied to this problem and more recent work has employed sophisticated models that allow for the sharing of information across genes.However,many recent gene expression studies have an experimental design with several conditions that requires an even more involved hypothesis testing approach. In this paper, we use a hierarchical Bayesian model to address the situation where there are many hypotheses that must be simultaneously tested for each gene. In addition to having many hypotheses within each gene, our analysis also addresses the more typical multiple comparison issue of testing many genes simultaneously. We illustrate our approach with an application to a study of genes involved in obstructive sleep apnea in humans

Molecular signatures of obstructive sleep apnea in adults: a review and perspective

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldThe consequences of obstructive sleep apnea (OSA) are largely mediated by chronic intermittent hypoxia and sleep fragmentation. The primary molecular domains affected are sympathetic activity, oxidative stress and inflammation. Other affected domains include adipokines, adhesion molecules and molecules that respond to endoplasmic reticulum stress. Changes in molecular domains affected by OSA, assessed in blood and/or urine, can provide a molecular signature for OSA that could potentially be used diagnostically and to predict who is likely to develop different OSA-related comorbidities. High-throughput discovery strategies such as microarrays, assessing changes in gene expression in circulating blood cells, have the potential to find new candidates and pathways thereby expanding the molecular signatures for OSA. More research is needed to fully understand the pathophysiological significance of these molecular signatures and their relationship with OSA comorbidities. Many OSA subjects are obese, and obesity is an independent risk factor for many comorbidities associated with OSA. Moreover, obesity affects the same molecular pathways as OSA. Thus, a challenge to establishing a molecular signature for OSA is to separate the effects of OSA from obesity. We propose that the optimal strategy is to evaluate the temporal changes in relevant molecular pathways during sleep and, in particular, the alterations from before to after sleep when assessed in blood and/or urine. Such changes will be at least partly a consequence of chronic intermittent hypoxia and sleep fragmentation that occurs during sleep

Sue Martin, Waikerie, South Australia, ca. 1975 [picture] /

Part of: Sheilas, a tribute to Australian women collection, ca. 1975.; Sue Martin, Australian Gliding Champion, 1971, lived in Waikerie, a noted gliding centre.; Title devised by cataloguer based on information supplied by photographer.; Also available in an electronic version via the internet at: http://nla.gov.au/nla.pic-vn4227640

Molecular signatures of obstructive sleep apnea in adults: a review and perspective

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldThe consequences of obstructive sleep apnea (OSA) are largely mediated by chronic intermittent hypoxia and sleep fragmentation. The primary molecular domains affected are sympathetic activity, oxidative stress and inflammation. Other affected domains include adipokines, adhesion molecules and molecules that respond to endoplasmic reticulum stress. Changes in molecular domains affected by OSA, assessed in blood and/or urine, can provide a molecular signature for OSA that could potentially be used diagnostically and to predict who is likely to develop different OSA-related comorbidities. High-throughput discovery strategies such as microarrays, assessing changes in gene expression in circulating blood cells, have the potential to find new candidates and pathways thereby expanding the molecular signatures for OSA. More research is needed to fully understand the pathophysiological significance of these molecular signatures and their relationship with OSA comorbidities. Many OSA subjects are obese, and obesity is an independent risk factor for many comorbidities associated with OSA. Moreover, obesity affects the same molecular pathways as OSA. Thus, a challenge to establishing a molecular signature for OSA is to separate the effects of OSA from obesity. We propose that the optimal strategy is to evaluate the temporal changes in relevant molecular pathways during sleep and, in particular, the alterations from before to after sleep when assessed in blood and/or urine. Such changes will be at least partly a consequence of chronic intermittent hypoxia and sleep fragmentation that occurs during sleep