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PubMed2025

Asymmetric integration of various cancer datasets for identifying risk-associated variants and genes.

MOTIVATION: Cancer genomic research provides an opportunity to identify cancer risk-associated genes, but often suffers from undesirable low statistical power due to a limited sample size. Integrated analysis with different cancers has the potential to enhance statistical power for identifying pan-cancer risk genes. However, substantial heterogeneity across various cancers makes this challenging. RESULTS: Recently, a novel asymmetric integration method was developed that can deal with data heterogeneity and exclude unhelpful datasets from the analysis. We adapted and applied this method to integrate genotype datasets with matched case and control individuals from the Michigan Genomics Initiative, using each cancer as the primary dataset of interest and the other cancers as auxiliary datasets, respectively. Conditional logistic regression models were coupled with the asymmetric integrated framework to handle the matched case-control study design and permutation tests were performed to control for false discovery rates (FDRs). At the same FDR level, the integrated analysis found more potential genetic variants and genes that are associated with the risks of various cancers, showcasing the promise of the proposed approach for integrated analysis of cancer datasets. AVAILABILITY AND IMPLEMENTATION: Our method is available as source code at https://github.com/rxxwang/integrate_cancer.

Journal Article↗
PubMed1999

ROC analysis of statistical methods used in functional MRI: individual subjects.

The complicated structure of fMRI signals and associated noise sources make it difficult to assess the validity of various steps involved in the statistical analysis of brain activation. Most methods used for fMRI analysis assume that observations are independent and that the noise can be treated as white gaussian noise. These assumptions are usually not true but it is difficult to assess how severely these assumptions are violated and what are their practical consequences. In this study a direct comparison is made between the power of various analytical methods used to detect activations, without reference to estimates of statistical significance. The statistics used in fMRI are treated as metrics designed to detect activations and are not interpreted probabilistically. The receiver operator characteristic (ROC) method is used to compare the efficacy of various steps in calculating an activation map in the study of a single subject based on optimizing the ratio of the number of detected activations to the number of false-positive findings. The main findings are as follows: Preprocessing. The removal of intensity drifts and high-pass filtering applied on the voxel time-course level is beneficial to the efficacy of analysis. Temporal normalization of the global image intensity, smoothing in the temporal domain, and low-pass filtering do not improve power of analysis. Choices of statistics. the cross-correlation coefficient and t-statistic, as well as nonparametric Mann-Whitney statistics, prove to be the most effective and are similar in performance, by our criterion. Task design. the proper design of task protocols is shown to be crucial. In an alternating block design the optimal block length is be approximately 18 s. Spatial clustering. an initial spatial smoothing of images is more efficient than cluster filtering of the statistical parametric activation maps.

Brain↗
PubMed1984

An evaluation of three statistics of structured exploratory data analysis.

The power of structured exploratory data analysis (SEDA) to discriminate among major genic, polygenic, and nongenetic determination of phenotypes was investigated using computer simulation. Three classes of SEDA indices (the major gene index, the offspring between parents function, and the midparent-child correlation coefficient) were evaluated. These three statistics, in combination, were reasonably sensitive in detecting the presence of a major locus and in discriminating between phenotypes with genetic effects and those with no genetic component. However, they were unable to discriminate between major genic and polygenically determined phenotypic models.

Chromosome Mapping↗
PubMed2024

PoweREST: Statistical Power Estimation for Spatial Transcriptomics Experiments to Detect Differentially Expressed Genes Between Two Conditions.

Recent advancements in Spatial Transcriptomics (ST) have significantly enhanced biological research in various domains. However, the high cost of current ST data generation techniques restricts its application in large-scale population studies. Consequently, there is a pressing need to maximize the use of available resources to achieve robust statistical power. One fundamental question in ST analysis is to detect differentially expressed genes (DEGs) among different conditions using ST data. Such DEG analysis is often performed but the associated power calculation is rarely discussed in the literature. To address this gap, we introduce, PoweREST (https://github.com/lanshui98/PoweREST), a power estimation tool designed to support power calculation of DEG detection with 10X Genomics Visium data. PoweREST enables power estimation both before any ST experiments or after preliminary data are collected, making it suitable for a wide variety of power analyses in ST studies. We also provide a user-friendly, program-free web application (https://lanshui.shinyapps.io/PoweREST/), allowing users to interactively calculate and visualize the study power along with relevant the parameters.

Differentially expressed genes↗
PubMed2002

Coronary artery pattern and outcome of arterial switch operation for transposition of the great arteries: a meta-analysis.

BACKGROUND: Prior studies of coronary pattern and outcome after arterial switch operation (ASO) for transposition of the great arteries (TGA) have been hindered by limited statistical power. This meta-analysis assesses the effect of coronary anatomy on post-ASO mortality, both overall and adjusted for time. METHODS AND RESULTS: A literature search revealed 9 independent series that reported post-ASO mortality by coronary pattern in a total of 1942 patients. Odds ratios comparing all-cause mortality in patients with usual versus variant coronary patterns were calculated and combined by use of an empirical Bayesian model. Single coronary patterns, both of which loop around the great vessels, were associated with significant mortality (OR 2.9, 95% CI 1.3 to 6.8), whereas looping patterns that arose from 2 separate ostia were not (OR 1.2, 95% CI 0.8 to 1.9). This latter group includes patients with the most common variant, circumflex from right coronary artery. Patients with an intramural coronary artery had the greatest mortality (OR 6.5, 95% CI 2.9 to 14.2). Overall, patients with any variant coronary pattern had nearly twice the mortality seen in those with the usual pattern (OR 1.7, 95% CI 1.3 to 2.4). Single ostium patterns and intramural coronary arteries remained associated with significant added mortality after adjustment for time-trend effects. CONCLUSIONS: Over the past 2 decades, patients with common coronary variants have undergone ASO without added mortality compared with those with the usual coronary pattern. Those with intramural or single coronary arteries have significant added mortality that has persisted over time.

Coronary Vessel Anomalies↗
PubMed1979

Standardised method of determining vibratory perception thresholds for diagnosis and screening in neurological investigation.

Vibration threshold determinations were made by means of an electromagnetic vibrator at three sites (carpal, tibial, and tarsal), which were primarily selected for examining patients with polyneuropathy. Because of the vast variation demonstrated for both vibrator output and tissue damping, the thresholds were expressed in terms of amplitude of stimulator movement measured by means of an accelerometer, instead of applied voltage which is commonly used. Statistical analysis revealed a higher power of discimination for amplitude measurements at all three stimulus sites. Digital read-out gave the best statistical result and was also most practical. Reference values obtained from 110 healthy males, 10 to 74 years of age, were highly correlated with age for both upper and lower extremities. The variance of the vibration perception threshold was less than that of the disappearance threshold, and determination of the perception threshold alone may be sufficient in most cases.

Adolescent↗
PubMed2006

Mixed-effects logistic approach for association following linkage scan for complex disorders.

An association study to identify possible causal single nucleotide polymorphisms following linkage scanning is a popular approach for the genetic dissection of complex disorders. However, in association studies cases and controls are assumed to be independent, i.e., genetically unrelated. Choosing a single affected individual per family is statistically inefficient and leads to a loss of power. On the other hand, because of the relatedness of family members, using affected family members and unrelated normal controls directly leads to false-positive results in association studies. In this paper we propose a new approach using mixed-model logistic regression, in which associations are performed using family members and unrelated controls. Thus, the important genetic information can be obtained from family members while retaining high statistical power. To examine the properties of this new approach we developed an efficient algorithm, to simulate environmental risk factors and the genotypes at both the disease locus and a marker locus with and without linkage disequilibrium (LD) in families. Extensive simulation studies showed that our approach can effectively control the type-I error probability. Our approach is better than family-based designs such as TDT, because it allows the use of unrelated cases and controls and uses all of the affected members for whom DNA samples are possibly already available. Our approach also allows the inclusion of covariates such as age and smoking status. Power analysis showed that our method has higher statistical power than recent likelihood ratio-based methods when environmental factors contribute to disease susceptibility, which is true for most complex human disorders. Our method can be further extended to accommodate more complex pedigree structures.

Algorithms↗
PubMed1987

Efficacy of psychoeducational interventions on pain, depression, and disability in people with arthritis: a meta-analysis.

Meta-analysis is a technique which combines data from several properly and similarly designed controlled studies so as to increase the power of the relevant statistical analysis. Fifteen studies on the effects of psychoeducational interventions on disability, pain and depression in individuals with chronic rheumatoid arthritis or osteoarthritis were analyzed by this method. The results indicate that patient education can indeed contribute to improving the health status of such patients.

Adult↗
PubMed1991

Issue of statistical power in comparative evaluations of minimal and intensive controlled drinking interventions.

An analysis of recent studies of minimal and intensive cognitive-behavioural treatments for problem drinking was undertaken to decide to whether a lack of statistical power explains the failure of the majority of studies to find a difference in outcome between these two types of treatment. Although the sample sizes have typically been small (n = 12-21), the analysis suggests that low statistical power is unlikely to be the explanation for the majority of null findings. It seems more likely that the difference in outcome between one positive study and the majority of null results reflects some combination of differences in the type of clients who were treated, the therapists' experience, and the type of intensive therapy that was provided. The low power of these studies demonstrates the desirability of researchers calculating the sample size required to an effect before commencing an outcome study. If they continue to undertake studies with small sample sizes, then they should refrain from inferring that the failure to reject a null hypothesis means that there is no difference between treatments.

Alcohol Drinking↗
PubMed1997

Updated results of the trials of screening mammography.

Most analysts agree that screening women for breast cancer can reduce the death rate by at least 25% to 30%. In 1993 the National Cancer Institute created a great deal of confusion among women and their physicians by withdrawing support for screening women aged 40 to 49 years. The controversy arose as a result of the inappropriate and scientifically insupportable analysis of data from the early results from the randomized controlled trials of screening. Despite that the trials were not designed to evaluate women aged 40 to 49 years as a separate subgroup and that they lacked the statistical power to permit legitimate analysis of this subgroup, women aged 40 to 49 years were analyzed separately, and erroneous conclusions were drawn. In an effort to justify these conclusions, other data have been analyzed improperly to try to suggest that significant screening parameters change at menopause or at the age of 50, whereas the facts do not support any abrupt change. There are no parameters such as breast density, cancer detection rate, or positive predictive value that change abruptly at age 50 or any other age. With longer follow-up of the screening trial data and the commensurately greater statistical power, the most recent meta-analyses provide statistically significant proof that screening can reduce the death rate from breast cancer for women aged 40 to 49 years by at least 24%.

Adult↗
PubMed2003

Ordered-subsets linkage analysis detects novel Alzheimer disease loci on chromosomes 2q34 and 15q22.

Alzheimer disease (AD) is a complex disorder characterized by a wide range, within and between families, of ages at onset of symptoms. Consideration of age at onset as a covariate in genetic-linkage studies may reduce genetic heterogeneity and increase statistical power. Ordered-subsets analysis includes continuous covariates in linkage analysis by rank ordering families by a covariate and summing LOD scores to find a subset giving a significantly increased LOD score relative to the overall sample. We have analyzed data from 336 markers in 437 multiplex (>/=2 sampled individuals with AD) families included in a recent genomic screen for AD loci. To identify genetic heterogeneity by age at onset, families were ordered by increasing and decreasing mean and minimum ages at onset. Chromosomewide significance of increases in the LOD score in subsets relative to the overall sample was assessed by permutation. A statistically significant increase in the nonparametric multipoint LOD score was observed on chromosome 2q34, with a peak LOD score of 3.2 at D2S2944 (P=.008) in 31 families with a minimum age at onset between 50 and 60 years. The LOD score in the chromosome 9p region previously linked to AD increased to 4.6 at D9S741 (P=.01) in 334 families with minimum age at onset between 60 and 75 years. LOD scores were also significantly increased on chromosome 15q22: a peak LOD score of 2.8 (P=.0004) was detected at D15S1507 (60 cM) in 38 families with minimum age at onset >/=79 years, and a peak LOD score of 3.1 (P=.0006) was obtained at D15S153 (62 cM) in 43 families with mean age at onset >80 years. Thirty-one families were contained in both 15q22 subsets, indicating that these results are likely detecting the same locus. There is little overlap in these subsets, underscoring the utility of age at onset as a marker of genetic heterogeneity. These results indicate that linkage to chromosome 9p is strongest in late-onset AD and that regions on chromosome 2q34 and 15q22 are linked to early-onset AD and very-late-onset AD, respectively.

Age of Onset↗
PubMed2004

Improving the spatial specificity of canonical correlation analysis in fMRI.

The contrast-to-noise ratio (CNR) is often very low in fMRI data, and standard univariate methods suffer from a loss of sensitivity in the context of noise. The increased power of a multivariate statistical analysis method known as canonical correlation analysis (CCA) in fMRI studies with low CNR was established previously. However, CCA in its conventional form has weak spatial specificity. In this work we propose a new assignment scheme to rectify this problem. It is shown that the new method has improved spatial specificity as well as sensitivity compared to conventional CCA for detecting activation patterns in fMRI.

Adult↗
PubMed2003

[Application of synthetic aperture magnetometry for epilepsy surgery].

Recently developed synthetic aperture magnetometry (SAM) is a new MEG signal analysis introducing a high performance spatial filtering technique. SAM is not an inverse solution like dipole analysis, but rather an adaptive beamformer for estimating source activity at each selected voxel inside of the brain. SAM can estimate source changes as a function of time, or power changes subjected to statistical analysis from the non-averaged raw MEG data. Thus this method enables to display the regional currentodensitogram of the arbitrary selected brain tissue as if depth electrodes were inserted (SAM virtual sensor), and to detect the origin of epileptic discharges and their spread. By applying statistical discrimination, SAM can also demonstrate the spatial distribution of event-related changes of brain rhythm (SAM statistical method), in other words activated cerebral cortex during task performance. We will present the usefulness of noninvasive SAM methods in epilepsy surgery detecting the epileptogenic zone by SAM virtual sensor method as well as eloquent brain by SAM statistical method.

Cerebral Cortex↗
PubMed2001

Lack of interaction between asbestos exposure and glutathione S-transferase M1 and T1 genotypes in lung carcinogenesis.

An interaction between occupational carcinogens and genetic susceptibility factors in determining individual lung cancer risk is biologically plausible, but the interpretation of available studies are limited by the small number of exposed subjects. We selected from the international database on Genetic Susceptibility and Environmental Carcinogens the studies of lung cancer that included information on metabolic polymorphisms and occupational exposures. Adequate data were available for asbestos exposure and GSTM1 (five studies) and GSTT1 (three studies) polymorphisms. For GSTM1, the pooled analysis included 651 cases and 983 controls. The odds ratio (OR) of lung cancer was 2.0 [95% confidence interval (CI) 1.4-2.7] for asbestos exposure and 1.1 (95% CI 0.9-1.4) for GSTM1-null genotype. The OR of interaction between asbestos and GSTM1 polymorphism was 1.1 (95% CI 0.6-2.1) based on 54 cases and 53 controls who were asbestos exposed and GSTM1 null. The case-only approach, which was based on 869 lung cancer cases and had an 80% power to detect an OR of interaction of 1.56, also provided lack of evidence of interaction. The analysis of possible interaction between GSTT1 polymorphism and asbestos exposure in relation to lung cancer was based on 619 cases. The prevalence OR of GSTT1-null genotype and asbestos exposure was 1.1 (95% CI 0.6-2.0). Our results do not support the hypothesis that the risk of lung cancer after asbestos exposure differs according to GSTM1 genotype. The low statistical power of the pooled analysis for GSTT1 genotypes hampered any firm conclusion. No adequate data were available to assess other interactions between occupational exposures and metabolic polymorphisms.

Adult↗
PubMed1994

The molecular chaperone TF55. Assessment of symmetry.

TF55-like factor from Sulfolobus solfataricus was purified to homogeneity and analyzed by electron microscopy and image analysis to determine the symmetries of these particles. Three different procedures were used to analyze the electron micrographs: (1) fuzzy-set based classification of the particles according to their rotational power spectra; (2) multivariate statistical analysis based on singular value decomposition; (3) circular harmonic analysis. Averages obtained from the three methods show unequivocally that the TF55-like complex presents a 9-fold symmetry.

Archaeal Proteins↗
PubMed2000

[Evidence-based medicine. Input of epidemiologic studies].

Epidemiological studies, more specifically those related to analytical epidemiology are a major determinant of evidence-based medicine. When classifying the value of the different epidemiological studies, based on their level of causality, cohort studies are ranked higher than case-control studies, mainly due to the fact that they allow direct collection of information on exposition to risk factors and health consequences. However, case-control studies can also provide an important information, if a specific effort is dedicated to the analyses of the circumstances of the exposition. Meta-analysis increases, by pooling them, the statistical power of individual studies of limited size. Meta-analysis can also be considered as an important source of evidence in the perspective of evidence-based medicine.

Case-Control Studies↗