Tests for comparison of multiple endpoints with application to omics data

2018 ◽  
Vol 17 (1) ◽  
Author(s):  
Marco Marozzi
Keyword(s):  
Small Sample ◽  
Omics Data ◽  
Interpoint Distance ◽  
Multiple Endpoints ◽  
Normality Assumption ◽  
Dependence Relations ◽  
Nonparametric Combination ◽  
Complex Dependence ◽  
Small Sample Sizes ◽  
Low Dimensional

AbstractIn biomedical research, multiple endpoints are commonly analyzed in “omics” fields like genomics, proteomics and metabolomics. Traditional methods designed for low-dimensional data either perform poorly or are not applicable when analyzing high-dimensional data whose dimension is generally similar to, or even much larger than, the number of subjects. The complex biochemical interplay between hundreds (or thousands) of endpoints is reflected by complex dependence relations. The aim of the paper is to propose tests that are very suitable for analyzing omics data because they do not require the normality assumption, are powerful also for small sample sizes, in the presence of complex dependence relations among endpoints, and when the number of endpoints is much larger than the number of subjects. Unbiasedness and consistency of the tests are proved and their size and power are assessed numerically. It is shown that the proposed approach based on the nonparametric combination of dependent interpoint distance tests is very effective. Applications to genomics and metabolomics are discussed.

scholarly journals A Machine Learning Approach to Reveal the NeuroPhenotypes of Autisms

2019 ◽  
Vol 29 (07) ◽  
pp. 1850058 ◽  
Author(s):  
Juan M. Górriz ◽  
Javier Ramírez ◽  
F. Segovia ◽  
Francisco J. Martínez ◽  
Meng-Chuan Lai ◽  
...  
Keyword(s):  
Machine Learning ◽  
Brain Structure ◽  
Feature Space ◽  
Classification Problem ◽  
Small Sample ◽  
Biological Sex ◽  
Machine Learning Approach ◽  
Learning Machine ◽  
Small Sample Sizes ◽  
Low Dimensional

Although much research has been undertaken, the spatial patterns, developmental course, and sexual dimorphism of brain structure associated with autism remains enigmatic. One of the difficulties in investigating differences between the sexes in autism is the small sample sizes of available imaging datasets with mixed sex. Thus, the majority of the investigations have involved male samples, with females somewhat overlooked. This paper deploys machine learning on partial least squares feature extraction to reveal differences in regional brain structure between individuals with autism and typically developing participants. A four-class classification problem (sex and condition) is specified, with theoretical restrictions based on the evaluation of a novel upper bound in the resubstitution estimate. These conditions were imposed on the classifier complexity and feature space dimension to assure generalizable results from the training set to test samples. Accuracies above [Formula: see text] on gray and white matter tissues estimated from voxel-based morphometry (VBM) features are obtained in a sample of equal-sized high-functioning male and female adults with and without autism ([Formula: see text], [Formula: see text]/group). The proposed learning machine revealed how autism is modulated by biological sex using a low-dimensional feature space extracted from VBM. In addition, a spatial overlap analysis on reference maps partially corroborated predictions of the “extreme male brain” theory of autism, in sexual dimorphic areas.

scholarly journals Variable selection in omics data: A practical evaluation of small sample sizes

PLoS ONE ◽  
2018 ◽  
Vol 13 (6) ◽  
pp. e0197910 ◽  
Author(s):  
Alexander Kirpich ◽  
Elizabeth A. Ainsworth ◽  
Jessica M. Wedow ◽  
Jeremy R. B. Newman ◽  
George Michailidis ◽  
...  
Keyword(s):  
Variable Selection ◽  
Small Sample ◽  
Omics Data ◽  
Sample Sizes ◽  
Practical Evaluation ◽  
Small Sample Sizes

scholarly journals Integrating multi-omics data with deep learning for predicting cancer prognosis

2019 ◽  
Author(s):  
Hua Chai ◽  
Xiang Zhou ◽  
Zifeng Cui ◽  
Jiahua Rao ◽  
Zheng Hu ◽  
...  
Keyword(s):  
Deep Learning ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Small Sample ◽  
The Cancer Genome Atlas ◽  
Cancer Prognosis ◽  
Omics Data ◽  
Hazards Model ◽  
Small Sample Sizes ◽  
The Impact

AbstractMotivationAccurately predicting cancer prognosis is necessary to choose precise strategies of treatment for patients. One of effective approaches in the prediction is the integration of multi-omics data, which reduces the impact of noise within single omics data. However, integrating multi-omics data brings large number of redundant variables and relative small sample sizes. In this study, we employed Autoencoder networks to extract important features that were then input to the proportional hazards model to predict the cancer prognosis.ResultsThe method was applied to 12 common cancers from the Cancer Genome Atlas. The results show that the multi-omics averagely improves 4.1% C-index for prognosis prediction over single mRNA data, and our method outperforms previous approaches by at least 7.4%. A comparison of the contribution of single omics data show that mRNA contributes the most, followed by the DNA methylation, miRNA, and the copy number variation. In the case study for differential gene expression analysis, we identified 161 differentially expressed genes in the cervical cancer, among which 77 genes (65.8%) have been proven to be associated with cancer. In addition, we performed the cross-cancer test where the model trained on one cancer was used to predict the prognosis of another cancer, and found 23 pairs of cancers have a C-index larger than 0.5, with the largest value of 0.68. Thus, this study has provided a deep learning framework to effectively integrate multiple omics data to predict cancer prognosis.

Integrating Visual and Bayesian Statistical Analyses in Single Case Experimental Research to Evaluate the Effectiveness and Magnitude of a Comprehensive Behavioral Intervention

2018 ◽  
Author(s):  
Prathiba Natesan ◽  
Smita Mehta
Keyword(s):  
Behavioral Intervention ◽  
Effect Size ◽  
Rate Ratio ◽  
Visual Analysis ◽  
Single Case ◽  
Small Sample ◽  
Statistical Analyses ◽  
Data Types ◽  
Ratio Effect ◽  
Small Sample Sizes

Single case experimental designs (SCEDs) have become an indispensable methodology where randomized control trials may be impossible or even inappropriate. However, the nature of SCED data presents challenges for both visual and statistical analyses. Small sample sizes, autocorrelations, data types, and design types render many parametric statistical analyses and maximum likelihood approaches ineffective. The presence of autocorrelation decreases interrater reliability in visual analysis. The purpose of the present study is to demonstrate a newly developed model called the Bayesian unknown change-point (BUCP) model which overcomes all the above-mentioned data analytic challenges. This is the first study to formulate and demonstrate rate ratio effect size for autocorrelated data, which has remained an open question in SCED research until now. This expository study also compares and contrasts the results from BUCP model with visual analysis, and rate ratio effect size with nonoverlap of all pairs (NAP) effect size. Data from a comprehensive behavioral intervention are used for the demonstration.

No Evidence that Experiencing Physical Warmth Promotes Interpersonal Warmth: Two Failures to Replicate Williams and Bargh (2008)

2018 ◽  
Author(s):  
Christopher Chabris ◽  
Patrick Ryan Heck ◽  
Jaclyn Mandart ◽  
Daniel Jacob Benjamin ◽  
Daniel J. Simons
Keyword(s):  
Null Hypothesis ◽  
Small Sample ◽  
Sample Sizes ◽  
Double Blind ◽  
Bayesian Analyses ◽  
Physical Warmth ◽  
Small Sample Sizes ◽  
Interpersonal Warmth

Williams and Bargh (2008) reported that holding a hot cup of coffee caused participants to judge a person’s personality as warmer, and that holding a therapeutic heat pad caused participants to choose rewards for other people rather than for themselves. These experiments featured large effects (r = .28 and .31), small sample sizes (41 and 53 participants), and barely statistically significant results. We attempted to replicate both experiments in field settings with more than triple the sample sizes (128 and 177) and double-blind procedures, but found near-zero effects (r = –.03 and .02). In both cases, Bayesian analyses suggest there is substantially more evidence for the null hypothesis of no effect than for the original physical warmth priming hypothesis.

scholarly journals Non-Invasive Monitoring of Adrenocortical Activity in Three Sympatric Desert Gerbil Species

Animals ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 75
Author(s):  
Álvaro Navarro-Castilla ◽  
Mario Garrido ◽  
Hadas Hawlena ◽  
Isabel Barja
Keyword(s):  
Small Sample ◽  
Post Injection ◽  
Control Groups ◽  
Treatment Groups ◽  
Adrenocortical Activity ◽  
Non Invasive ◽  
Endocrine Status ◽  
Corticosterone Metabolites ◽  
Small Sample Sizes ◽  
Fecal Corticosterone Metabolites

The study of the endocrine status can be useful to understand wildlife responses to the changing environment. Here, we validated an enzyme immunoassay (EIA) to non-invasively monitor adrenocortical activity by measuring fecal corticosterone metabolites (FCM) in three sympatric gerbil species (Gerbillus andersoni, G. gerbillus and G. pyramidum) from the Northwestern Negev Desert’s sands (Israel). Animals included into treatment groups were injected with adrenocorticotropic hormone (ACTH) to stimulate adrenocortical activity, while control groups received a saline solution. Feces were collected at different intervals and FCM were quantified by an EIA. Basal FCM levels were similar in the three species. The ACTH effect was evidenced, but the time of FCM peak concentrations appearance differed between the species (6–24 h post-injection). Furthermore, FCM peak values were observed sooner in G. andersoni females than in males (6 h and 18 h post-injection, respectively). G. andersoni and G. gerbillus males in control groups also increased FCM levels (18 h and 48 h post-injection, respectively). Despite the small sample sizes, our results confirmed the EIA suitability for analyzing FCM in these species as a reliable indicator of the adrenocortical activity. This study also revealed that close species, and individuals within a species, can respond differently to the same stressor.

scholarly journals Use of Antiplatelet Agents Decreases the Positive Predictive Value of Fecal Immunochemical Tests for Colorectal Cancer but Does Not Affect Their Sensitivity

2021 ◽  
Vol 11 (6) ◽  
pp. 497
Author(s):  
Yoonsuk Jung ◽  
Eui Im ◽  
Jinhee Lee ◽  
Hyeah Lee ◽  
Changmo Moon
Keyword(s):  
Colorectal Cancer ◽  
Large Scale ◽  
Screening Program ◽  
Antiplatelet Agents ◽  
Population Based ◽  
Small Sample ◽  
Antithrombotic Agents ◽  
Predictive Values ◽  
Prescription Rates ◽  
Small Sample Sizes

Previous studies have evaluated the effects of antithrombotic agents on the performance of fecal immunochemical tests (FITs) for the detection of colorectal cancer (CRC), but the results were inconsistent and based on small sample sizes. We studied this topic using a large-scale population-based database. Using the Korean National Cancer Screening Program Database, we compared the performance of FITs for CRC detection between users and non-users of antiplatelet agents and warfarin. Non-users were matched according to age and sex. Among 5,426,469 eligible participants, 768,733 used antiplatelet agents (mono/dual/triple therapy, n = 701,683/63,211/3839), and 19,569 used warfarin, while 4,638,167 were non-users. Among antiplatelet agents, aspirin, clopidogrel, and cilostazol ranked first, second, and third, respectively, in terms of prescription rates. Users of antiplatelet agents (3.62% vs. 4.45%; relative risk (RR): 0.83; 95% confidence interval (CI): 0.78–0.88), aspirin (3.66% vs. 4.13%; RR: 0.90; 95% CI: 0.83–0.97), and clopidogrel (3.48% vs. 4.88%; RR: 0.72; 95% CI: 0.61–0.86) had lower positive predictive values (PPVs) for CRC detection than non-users. However, there were no significant differences in PPV between cilostazol vs. non-users and warfarin users vs. non-users. For PPV, the RR (users vs. non-users) for antiplatelet monotherapy was 0.86, while the RRs for dual and triple antiplatelet therapies (excluding cilostazol) were 0.67 and 0.22, respectively. For all antithrombotic agents, the sensitivity for CRC detection was not different between users and non-users. Use of antiplatelet agents, except cilostazol, may increase the false positives without improving the sensitivity of FITs for CRC detection.

scholarly journals Perioperative digital behaviour change interventions for reducing alcohol consumption, improving dietary intake, increasing physical activity and smoking cessation: a scoping review

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Katarina Åsberg ◽  
Marcus Bendtsen
Keyword(s):  
Physical Activity ◽  
Smoking Cessation ◽  
Behaviour Change ◽  
Scoping Review ◽  
Text Messaging ◽  
Text Message ◽  
Feasibility Studies ◽  
Small Sample ◽  
Small Sample Sizes ◽  
Randomised Controlled

Abstract Background Evidence suggests that unhealthy lifestyle behaviours are modifiable risk factors for postoperative complications. Digital behaviour change interventions (DBCIs), for instance text messaging programs and smartphone apps, have shown promise in achieving lifestyle behaviour change in a wide range of clinical populations, and it may therefore be possible to reduce postoperative complications by supporting behaviour change perioperatively using digital interventions. This scoping review was conducted in order to identify existing research done in the area of perioperative DBCIs for reducing alcohol consumption, improving dietary intake, increasing physical activity and smoking cessation. Main text This scoping review included eleven studies covering a range of surgeries: bariatric, orthopaedic, cancer, transplantation and elective surgery. The studies were both randomised controlled trials and feasibility studies and investigated a diverse set of interventions: one game, three smartphone apps, one web-based program and five text message interventions. Feasibility studies reported user acceptability and satisfaction with the behaviour change support. Engagement data showed participation rates ranged from 40 to 90%, with more participants being actively engaged early in the intervention period. In conclusion, the only full-scale randomised controlled trial (RCT), text messaging ahead of bariatric surgery did not reveal any benefits with respect to adherence to preoperative exercise advice when compared to a control group. Two of the pilot studies, one text message intervention, one game, indicated change in a positive direction with respect to alcohol and tobacco outcomes, but between group comparisons were not done due to small sample sizes. The third pilot-study, a smartphone app, found between group changes for physical activity and alcohol, but not with respect to smoking cessation outcomes. Conclusion This review found high participant satisfaction, but shows recruitment and timing-delivery issues, as well as low retention to interventions post-surgery. Small sample sizes and the use of a variety of feasibility outcome measures prevent the synthesis of results and makes generalisation difficult. Future research should focus on defining standardised outcome measures, enhancing patient engagement and improving adherence to behaviour change prior to scheduled surgery.

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