Background: Examining residuals is a crucial step in statistical analysis to identify the discrepancies between models and data, and assess the overall model goodness-of-fit. In diagnosing normal linear regression models, both Pearson and deviance residuals are often used, which are equivalently and approximately standard normally distributed when the model fits the data adequately. However, when the response vari*able is discrete, these residuals are distributed far from normality and have nearly parallel curves according to the distinct discrete response values, imposing great challenges for visual inspection.Methods: Randomized quantile residuals (RQRs) were proposed in the literature by Dunn and Smyth (1996) to circumvent the problems in traditional residuals. However, this approach has not gained popularity partly due to the lack of investigation of its performance for count regression including zero-inflated models through simulation studies. Therefore, we assessed the normality of the RQRs and compared their performance with traditional residuals for diagnosing count regression models through a series of simulation studies. A real data analysis in health care utilization study for modeling the number of repeated emergency department visits was also presented.Results: Our results of the simulation studies demonstrated that RQRs have low type I error and great statistical power in comparisons to other residuals for detecting many forms of model misspecification for count regression models (non-linearity in covariate effect, over-dispersion, and zero inflation). Our real data analysis also showed that RQRs are effective in detecting misspecified distributional assumptions for count regression models.Conclusions: Our results for evaluating RQRs in comparison with traditional residuals provide further evidence on its advantages for diagnosing count regression models.

Falls pose major health problems to the middle-aged and older adults and may potentially lead to various levels of injuries. Sleep duration and disturbances have been shown to be associated with falls in literature; however, studies of the joint and distinct effects of those sleep problems are still sparse. To fill this gap, we aimed to determine the association between sleep duration, sleep disturbances and falls among middle-aged and older adults in China controlling for psychosocial, lifestyle, socio-demographical factors and comorbidity. Data were derived from the China Health and Retirement Longitudinal Study (CHARLS) based on multi-stage sampling designs, with respondents aged 50 and older. Associations were evaluated by using multiple logistic regression adjusting for confounders and complex survey design. To further determine if the association of sleep duration/disturbance and falls depends on age groups, the study data were divided into two samples (age 50–64 vs. age 65+) and comparison was made between the two age groups. Of the 12,759 respondents, 2172 (17%) had falls within the last 2 years. Our findings indicated that the participants who had nighttime sleep duration ≤5 were more likely to report falls than those who had nighttime sleep duration ≥6 h; whereas no association between nighttime sleep duration > 8 h and falls. Participants having sleep disturbances 1–2 days, or 3–4 days, and 5–7 days per week were also more likely to report falls than those who had no sleep disturbance. The nap sleep duration was not significantly associated with falls. Although the combined sample found both sleep duration and sleep disturbance to be strongly associated with falls after adjusting for various confounders, sleep disturbance was not significantly related to falls among participants aged 65 + . Our study suggested that there is an independent association between falls and short sleep duration and disturbed sleep among middle-aged and older adults in China. Findings underscore the need for evidence-based prevention and interventions targeting sleep duration and disturbance among this study population.

Background: Antimicrobial resistance (AMR) is a major threat to global public health because it makes standard treatments ineffective and contributes to the spread of infections. It is important to understand AMR’s biological mechanisms for the development of new drugs and more rapid and accurate clinical diagnostics. The increasing availability of whole-genome SNP (single nucleotide polymorphism) information, obtained from whole-genome sequence data, along with AMR profiles provides an opportunity to use feature selection in machine learning to find AMR-associated mutations. This work describes the use of a supervised feature selection approach using deep neural networks to detect AMR-associated genetic factors from whole-genome SNP data.Results: The proposed method, DNP-AAP (deep neural pursuit – average activation potential), was tested on aNeisseria gonorrhoeaedataset with paired whole-genome sequence data and resistance profiles to five commonly used antibiotics including penicillin, tetracycline, azithromycin, ciprofloxacin, and cefixime. The results show that DNP-AAP can effectively identify known AMR-associated genes inN. gonorrhoeae, and also provide a list of candidate genomic features (SNPs) that might lead to the discovery of novel AMR determinants. Logistic regression classifiers were built with the identified SNPs and the prediction AUCs (area under the curve) for penicillin, tetracycline, azithromycin, ciprofloxacin, and cefixime were 0.974, 0.969, 0.949, 0.994, and 0.976, respectively.Conclusions: DNP-AAP can effectively identify known AMR-associated genes inN. gonorrhoeae. It also provides a list of candidate genes and intergenic regions that might lead to novel AMR factor discovery. More generally, DNP-AAP can be applied to AMR analysis of any bacterial species with genomic variants and phenotype data. It can serve as a useful screening tool for microbiologists to generate genetic candidates for further lab experiments.

Microbiome data consists of operational taxonomic unit (OTU) counts characterized by zero-inflation, over-dispersion, and grouping structure among samples. Currently, statistical testing methods are commonly performed to identify OTUs that are associated with a phenotype. The limitations of statistical testing methods include that the validity of p-values/q-values depend sensitively on the correctness of models and that the statistical significance does not necessarily imply predictivity. Predictive analysis using methods such as LASSO is an alternative approach for identifying associated OTUs and for measuring the predictability of the phenotype variable with OTUs and other covariate variables. We investigate three strategies of performing predictive analysis: (1) LASSO: fitting a LASSO multinomial logistic regression model to all OTU counts with specific transformation; (2) screening+GLM: screening OTUs with q-values returned by fitting a GLMM to each OTU, then fitting a GLM model using a subset of selected OTUs; (3) screening+LASSO: fitting a LASSO to a subset of OTUs selected with GLMM. We have conducted empirical studies using three simulation datasets generated using Dirichlet-multinomial models and a real gut microbiome data related to Parkinson’s disease to investigate the performance of the three strategies for predictive analysis. Our simulation studies show that the predictive performance of LASSO with appropriate variable transformation works remarkably well on zero-inflated data. Our results of real data analysis show that Parkinson’s disease can be predicted based on selected OTUs after the binary transformation, age, and sex with high accuracy (Error Rate = 0.199, AUC = 0.872, AUPRC = 0.912). These results provide strong evidences of the relationship between Parkinson’s disease and the gut microbiome.