Code smells analysis for android applications and a solution for less battery consumption.

In the digitization era, the battery consumption factor plays a vital role for the devices that operate Android software, expecting them to deliver high performance and good maintainability.The study aims to analyze the Android-specific code smells, their impact on battery consumption, and the formulation of a mathematical model concerning static code metrics hampered by the code smells. We studied the impact on battery consumption by three Android-specific code smells, namely: No Low Memory Resolver (NLMR), Slow Loop (SL) and Unclosed Closable, considering 4,165 classes of 16 Android applications. We used a rule-based classification method that aids the refactoring ideology. Subsequently, multi-linear regression (MLR) modeling is used to evaluate battery usage against the software metrics of smelly code instances. Moreover, it was possible to devise a correlation for the software metric influenced by battery consumption and rule-based classifiers. The outcome confirms that the refactoring of the considered code smells minimizes the battery consumption levels. The refactoring method accounts for an accuracy of 87.47% cumulatively. The applied MLR model has an R-square value of 0.76 for NLMR and 0.668 for SL, respectively. This study can guide the developers towards a complete package for the focused development life cycle of Android code, helping them minimize smartphone battery consumption and use the saved battery lives for other operations, contributing to the green energy revolution in mobile devices.

Differential Item Functioning via Robust Scaling.

This paper proposes a method for assessing differential item functioning (DIF) in item response theory (IRT) models. The method does not require pre-specification of anchor items, which is its main virtue. It is developed in two main steps: first by showing how DIF can be re-formulated as a problem of outlier detection in IRT-based scaling and then tackling the latter using methods from robust statistics. The proposal is a redescending M-estimator of IRT scaling parameters that is tuned to flag items with DIF at the desired asymptotic type I error rate. Theoretical results describe the efficiency of the estimator in the absence of DIF and its robustness in the presence of DIF. Simulation studies show that the proposed method compares favorably to currently available approaches for DIF detection, and a real data example illustrates its application in a research context where pre-specification of anchor items is infeasible. The focus of the paper is the two-parameter logistic model in two independent groups, with extensions to other settings considered in the conclusion.

Evaluation and monitoring of the water quality of an Argentinian urban river applying multivariate statistics.

In this work, we present the water quality assessment of an urban river, the San Luis River, located in San Luis Province, Argentina. The San Luis River flows through two developing cities; hence, urban anthropic activities affect its water quality. The river was sampled spatially and temporally, evaluating ten physicochemical variables on each water sample. These data were used to calculate a Simplified Index of Water Quality in order to estimate river water quality and infer possible contamination sources. Data were statistically analyzed with the opensource software R, 4.1.0 version. Principal component analysis, cluster analysis, correlation matrices, and heatmap analysis were performed. Results indicated that water quality decreases in areas where anthropogenic activities take place. Robust inferential statistical analysis was performed, employing an alternative of multivariate analysis of variance (MANOVA), MANOVA.wide function. The most statistically relevant physicochemical variables associated with water quality decrease were used to develop a multiple linear regression model to estimate organic matter, reducing the variables necessary for continuous monitoring of the river and, hence, reducing costs. Given the limited information available in the region about the characteristics and recovery of this specific river category, the model developed is of vital importance since it can quickly detect anthropic alterations and contribute to the environmental management of the rivers. This model was also used to estimate organic matter at sites located in other similar rivers, obtaining satisfactory results.

From means to meaning in the study of sex/gender differences and similarities.

The incorporation of sex and gender (S/G) related factors is commonly acknowledged as a necessary step to advance towards more personalized diagnoses and treatments for somatic, psychiatric, and neurological diseases. Until now, most attempts to integrate S/G-related factors have been reduced to identifying average differences between females and males in behavioral/ biological variables. The present commentary questions this traditional approach by highlighting three main sets of limitations: 1) Issues stemming from the use of classic parametric methods to compare means; 2) challenges related to the ability of means to accurately represent the data within groups and differences between groups; 3) mean comparisons impose a results' binarization and a binary theoretical framework that precludes advancing towards precision medicine. Alternative methods free of these limitations are also discussed. We hope these arguments will contribute to reflecting on how research on S/G factors is conducted and could be improved.

Brain-inspired semantic data augmentation for multi-style images.

Data augmentation is an effective technique for automatically expanding training data in deep learning. Brain-inspired methods are approaches that draw inspiration from the functionality and structure of the human brain and apply these mechanisms and principles to artificial intelligence and computer science. When there is a large style difference between training data and testing data, common data augmentation methods cannot effectively enhance the generalization performance of the deep model. To solve this problem, we improve modeling Domain Shifts with Uncertainty (DSU) and propose a new brain-inspired computer vision image data augmentation method which consists of two key components, namely, using Robust statistics and controlling the Coefficient of variance for DSU (RCDSU) and Feature Data Augmentation (FeatureDA). RCDSU calculates feature statistics (mean and standard deviation) with robust statistics to weaken the influence of outliers, making the statistics close to the real values and improving the robustness of deep learning models. By controlling the coefficient of variance, RCDSU makes the feature statistics shift with semantic preservation and increases shift range. FeatureDA controls the coefficient of variance similarly to generate the augmented features with semantics unchanged and increase the coverage of augmented features. RCDSU and FeatureDA are proposed to perform style transfer and content transfer in the feature space, and improve the generalization ability of the model at the style and content level respectively. On Photo, Art Painting, Cartoon, and Sketch (PACS) multi-style classification task, RCDSU plus FeatureDA achieves competitive accuracy. After adding Gaussian noise to PACS dataset, RCDSU plus FeatureDA shows strong robustness against outliers. FeatureDA achieves excellent results on CIFAR-100 image classification task. RCDSU plus FeatureDA can be applied as a novel brain-inspired semantic data augmentation method with implicit robot automation which is suitable for datasets with large style differences between training and testing data.

Robust Identification of Differential Gene Expression Patterns from Multiple Transcriptomics Datasets for Early Diagnosis, Prognosis, and Therapies for Breast Cancer.

Background and Objectives: Breast cancer (BC) is one of the major causes of cancer-related death in women globally. Proper identification of BC-causing hub genes (HubGs) for prognosis, diagnosis, and therapies at an earlier stage may reduce such death rates. However, most of the previous studies detected HubGs through non-robust statistical approaches that are sensitive to outlying observations. Therefore, the main objectives of this study were to explore BC-causing potential HubGs from robustness viewpoints, highlighting their early prognostic, diagnostic, and therapeutic performance. Materials and Methods: Integrated robust statistics and bioinformatics methods and databases were used to obtain the required results. Results: We robustly identified 46 common differentially expressed genes (cDEGs) between BC and control samples from three microarrays (GSE26910, GSE42568, and GSE65194) and one scRNA-seq (GSE235168) dataset. Then, we identified eight cDEGs (COL11A1, COL10A1, CD36, ACACB, CD24, PLK1, UBE2C, and PDK4) as the BC-causing HubGs by the protein-protein interaction (PPI) network analysis of cDEGs. The performance of BC and survival probability prediction models with the expressions of HubGs from two independent datasets (GSE45827 and GSE54002) and the TCGA (The Cancer Genome Atlas) database showed that our proposed HubGs might be considered as diagnostic and prognostic biomarkers, where two genes, COL11A1 and CD24, exhibit better performance. The expression analysis of HubGs by Box plots with the TCGA database in different stages of BC progression indicated their early diagnosis and prognosis ability. The HubGs set enrichment analysis with GO (Gene ontology) terms and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways disclosed some BC-causing biological processes, molecular functions, and pathways. Finally, we suggested the top-ranked six drug molecules (Suramin, Rifaximin, Telmisartan, Tukysa Tucatinib, Lynparza Olaparib, and TG.02) for the treatment of BC by molecular docking analysis with the proposed HubGs-mediated receptors. Molecular docking analysis results also showed that these drug molecules may inhibit cancer-related post-translational modification (PTM) sites (Succinylation, phosphorylation, and ubiquitination) of hub proteins. Conclusions: This study's findings might be valuable resources for diagnosis, prognosis, and therapies at an earlier stage of BC.

Automated tuning of denoising algorithms for noise removal in chromatograms.

Different algorithms, such as the Savitzky-Golay filter and Whittaker smoother, have been proposed to improve the quality of experimental chromatograms. These approaches avoid excessive noise from hampering data analysis and as such allow an accurate detection and quantification of analytes. These algorithms require fine-tuning of their hyperparameters to regulate their roughness and flexibility. Traditionally, this fine-tuning is done manually until a signal is obtained that removes the noise while conserving valuable peak information. More objective and automated approaches are available, but these are usually method specific and/or require previous knowledge. In this work, the L-and V-curve, k-fold cross-validation, autocorrelation function and residual variance estimation approach are introduced as alternative automated and generally applicable parameter tuning methods. These methods do not require any previous information and are compatible with a multitude of denoising methods. Additionally, for k-fold cross-validation, autocorrelation function and residual variance estimation, a novel implementation based on median estimators is proposed to handle the specific shape of chromatograms, typically composed of alternating flat baselines and sharp peaks. These tuning methods are investigated in combination with four denoising methods; the Savitsky-Golay filter, Whittaker smoother, sparsity assisted signal smoother and baseline estimation and denoising using sparsity approach. It is demonstrated that the median estimators approach significantly improves the denoising and information conservation performance of relevant smoother-tuner combinations up to a factor 4 for simulated datasets and even up to a factor 10 for an experimental chromatogram. Moreover, the parameter tuning methods relying on residual variance estimation, k-fold cross-validation and autocorrelation function lead to similar small root-mean squared errors on the different simulated datasets and experimental chromatograms. The sparsity assisted signal smoother and baseline estimation and denoising using sparsity approach, which both rely on the use of sparsity, systematically outperform the two other methods and are hence most appropriate for chromatograms.

A Python package based on robust statistical analysis for serial crystallography data processing.

The term robustness in statistics refers to methods that are generally insensitive to deviations from model assumptions. In other words, robust methods are able to preserve their accuracy even when the data do not perfectly fit the statistical models. Robust statistical analyses are particularly effective when analysing mixtures of probability distributions. Therefore, these methods enable the discretization of X-ray serial crystallography data into two probability distributions: a group comprising true data points (for example the background intensities) and another group comprising outliers (for example Bragg peaks or bad pixels on an X-ray detector). These characteristics of robust statistical analysis are beneficial for the ever-increasing volume of serial crystallography (SX) data sets produced at synchrotron and X-ray free-electron laser (XFEL) sources. The key advantage of the use of robust statistics for some applications in SX data analysis is that it requires minimal parameter tuning because of its insensitivity to the input parameters. In this paper, a software package called Robust Gaussian Fitting library (RGFlib) is introduced that is based on the concept of robust statistics. Two methods are presented based on the concept of robust statistics and RGFlib for two SX data-analysis tasks: (i) a robust peak-finding algorithm and (ii) an automated robust method to detect bad pixels on X-ray pixel detectors.

A comprehensive identification of potential molecular targets and small drugs candidate for melanoma cancer using bioinformatics and network-based screening approach.

Melanoma is the third most common malignant skin tumor and has increased in morbidity and mortality over the previous decade due to its rapid spread into the bloodstream or lymphatic system. This study used integrated bioinformatics and network-based methodologies to reliably identify molecular targets and small molecular medicines that may be more successful for Melanoma diagnosis, prognosis and treatment. The statistical LIMMA approach utilized for bioinformatics analysis in this study found 246 common differentially expressed genes (cDEGs) between case and control samples from two microarray gene-expression datasets (GSE130244 and GSE15605). Protein-protein interaction network study revealed 15 cDEGs (PTK2, STAT1, PNO1, CXCR4, WASL, FN1, RUNX2, SOCS3, ITGA4, GNG2, CDK6, BRAF, AGO2, GTF2H1 and AR) to be critical in the development of melanoma (KGs). According to regulatory network analysis, the most important transcriptional and post-transcriptional regulators of DEGs and hub-DEGs are ten transcription factors and three miRNAs. We discovered the pathogenetic mechanisms of MC by studying DEGs' biological processes, molecular function, cellular components and KEGG pathways. We used molecular docking and dynamics modeling to select the four most expressed genes responsible for melanoma malignancy to identify therapeutic candidates. Then, utilizing the Connectivity Map (CMap) database, we analyzed the top 4-hub-DEGs-guided repurposable drugs. We validated four melanoma cancer drugs (Fisetin, Epicatechin Gallate, 1237586-97-8 and PF 431396) using molecular dynamics simulation with their target proteins. As a result, the results of this study may provide resources to researchers and medical professionals for the wet-lab validation of MC diagnosis, prognosis and treatments.Communicated by Ramaswamy H. Sarma.

A Robust Method for Detecting Item Misfit in Large-Scale Assessments.

Viable methods for the identification of item misfit or Differential Item Functioning (DIF) are central to scale construction and sound measurement. Many approaches rely on the derivation of a limiting distribution under the assumption that a certain model fits the data perfectly. Typical DIF assumptions such as the monotonicity and population independence of item functions are present even in classical test theory but are more explicitly stated when using item response theory or other latent variable models for the assessment of item fit. The work presented here provides a robust approach for DIF detection that does not assume perfect model data fit, but rather uses Tukey's concept of contaminated distributions. The approach uses robust outlier detection to flag items for which adequate model data fit cannot be established.

Detection of differential depressive symptom patterns in a cohort of perinatal women: an exploratory factor analysis using a robust statistics approach.

Background: Postpartum depression can take many forms. Different symptom patterns could have divergent implications for how we screen, diagnose, and treat postpartum depression. We sought to utilise a recently developed robust estimation algorithm to automatically identify differential patterns in depressive symptoms and subsequently characterise the individuals who exhibit different patterns. Methods: Depressive symptom data (N = 548) were collected from women with neuropsychiatric illnesses at two U.S. urban sites participating in a longitudinal observational study of stress across the perinatal period. Data were collected from Emory University between 1994 and 2012 and from the University of Arkansas for Medical Sciences between 2012 and 2017. We conducted an exploratory factor analysis of Beck Depression Inventory (BDI) items using a robust expectation-maximization algorithm, rather than a conventional expectation-maximization algorithm. This recently developed method enabled automatic detection of differential symptom patterns. We described differences in symptom patterns and conducted unadjusted and adjusted analyses of associations of symptom patterns with demographics and psychiatric histories. Findings: 53 (9.7%) participants were identified by the algorithm as having a different pattern of reported symptoms compared to other participants. This group had more severe symptoms across all items-especially items related to thoughts of self-harm and self-judgement-and differed in how their symptoms related to underlying psychological constructs. History of social anxiety disorder (OR: 4.0; 95% CI [1.9, 8.1]) and history of childhood trauma (for each 5-point increase, OR: 1.2; 95% CI [1.1, 1.3]) were significantly associated with this differential pattern after adjustment for other covariates. Interpretation: Social anxiety disorder and childhood trauma are associated with differential patterns of severe postpartum depressive symptoms, which might warrant tailored strategies for screening, diagnosis, and treatment to address these comorbid conditions. Funding: There are no funding sources to declare.

The DetectDeviatingCells algorithm was a useful addition to the toolkit for cellwise error detection in observational data.

OBJECTIVES: We evaluated the error detection performance of the DetectDeviatingCells (DDC) algorithm which flags data anomalies at observation (casewise) and variable (cellwise) level in continuous variables. We compared its performance to other approaches in a simulated dataset. STUDY DESIGN AND SETTING: We simulated height and weight data for hypothetical individuals aged 2-20 years. We changed a proportion of height values according to predetermined error patterns. We applied the DDC algorithm and other error-detection approaches (descriptive statistics, plots, fixed-threshold rules, classic, and robust Mahalanobis distance) and we compared error detection performance with sensitivity, specificity, likelihood ratios, predictive values, and receiver operating characteristic (ROC) curves. RESULTS: At our chosen thresholds error detection specificity was excellent across all scenarios for all methods and sensitivity was higher for multivariable and robust methods. The DDC algorithm performance was similar to other robust multivariable methods. Analysis of ROC curves suggested that all methods had comparable performance for gross errors (e.g., wrong measurement unit), but the DDC algorithm outperformed the others for more complex error patterns (e.g., transcription errors that are still plausible, although extreme). CONCLUSIONS: The DDC algorithm has the potential to improve error detection processes for observational data.

Inferring Cultural Landscapes with the Inverse Ising Model.

The space of possible human cultures is vast, but some cultural configurations are more consistent with cognitive and social constraints than others. This leads to a "landscape" of possibilities that our species has explored over millennia of cultural evolution. However, what does this fitness landscape, which constrains and guides cultural evolution, look like? The machine-learning algorithms that can answer these questions are typically developed for large-scale datasets. Applications to the sparse, inconsistent, and incomplete data found in the historical record have received less attention, and standard recommendations can lead to bias against marginalized, under-studied, or minority cultures. We show how to adapt the minimum probability flow algorithm and the Inverse Ising model, a physics-inspired workhorse of machine learning, to the challenge. A series of natural extensions-including dynamical estimation of missing data, and cross-validation with regularization-enables reliable reconstruction of the underlying constraints. We demonstrate our methods on a curated subset of the Database of Religious History: records from 407 religious groups throughout human history, ranging from the Bronze Age to the present day. This reveals a complex, rugged, landscape, with both sharp, well-defined peaks where state-endorsed religions tend to concentrate, and diffuse cultural floodplains where evangelical religions, non-state spiritual practices, and mystery religions can be found.

Identification of outlying observations for large-dimensional data.

This work proposes a two-stage procedure for identifying outlying observations in a large-dimensional data set. In the first stage, an outlier identification measure is defined by using a max-normal statistic and a clean subset that contains non-outliers is obtained. The identification of outliers can be deemed as a multiple hypothesis testing problem, then, in the second stage, we explore the asymptotic distribution of the proposed measure, and obtain the threshold of the outlying observations. Furthermore, in order to improve the identification power and better control the misjudgment rate, a one-step refined algorithm is proposed. Simulation results and two real data analysis examples show that, compared with other methods, the proposed procedure has great advantages in identifying outliers in various data situations.

Transcriptomic pan-cancer analysis using rank-based Bayesian inference.

The analysis of whole genomes of pan-cancer data sets provides a challenge for researchers, and we contribute to the literature concerning the identification of robust subgroups with clear biological interpretation. Specifically, we tackle this unsupervised problem via a novel rank-based Bayesian clustering method. The advantages of our method are the integration and quantification of all uncertainties related to both the input data and the model, the probabilistic interpretation of final results to allow straightforward assessment of the stability of clusters leading to reliable conclusions, and the transparent biological interpretation of the identified clusters since each cluster is characterized by its top-ranked genomic features. We applied our method to RNA-seq data from cancer samples from 12 tumor types from the Cancer Genome Atlas. We identified a robust clustering that mostly reflects tissue of origin but also includes pan-cancer clusters. Importantly, we identified three pan-squamous clusters composed of a mix of lung squamous cell carcinoma, head and neck squamous carcinoma, and bladder cancer, with different biological functions over-represented in the top genes that characterize the three clusters. We also found two novel subtypes of kidney cancer that show different prognosis, and we reproduced known subtypes of breast cancer. Taken together, our method allows the identification of robust and biologically meaningful clusters of pan-cancer samples.

Robust identification of common genomic biomarkers from multiple gene expression profiles for the prognosis, diagnosis, and therapies of pancreatic cancer.

Pancreatic cancer (PC) is one of the leading causes of cancer-related death globally. So, identification of potential molecular signatures is required for diagnosis, prognosis, and therapies of PC. In this study, we detected 71 common differentially expressed genes (cDEGs) between PC and control samples from four microarray gene-expression datasets (GSE15471, GSE16515, GSE71989, and GSE22780) by using robust statistical and machine learning approaches, since microarray gene-expression datasets are often contaminated by outliers due to several steps involved in the data generating processes. Then we detected 8 cDEGs (ADAM10, COL1A2, FN1, P4HB, ITGB1, ITGB5, ANXA2, and MYOF) as the PC-causing key genes (KGs) by the protein-protein interaction (PPI) network analysis. We validated the expression patterns of KGs between case and control samples by box plot analysis with the TCGA and GTEx databases. The proposed KGs showed high prognostic power with the random forest (RF) based prediction model and Kaplan-Meier-based survival probability curve. The KGs regulatory network analysis detected few transcriptional and post-transcriptional regulators for KGs. The cDEGs-set enrichment analysis revealed some crucial PC-causing molecular functions, biological processes, cellular components, and pathways that are associated with KGs. Finally, we suggested KGs-guided five repurposable drug molecules (Linsitinib, CX5461, Irinotecan, Timosaponin AIII, and Olaparib) and a new molecule (NVP-BHG712) against PC by molecular docking. The stability of the top three protein-ligand complexes was confirmed by molecular dynamic (MD) simulation studies. The cross-validation and some literature reviews also supported our findings. Therefore, the finding of this study might be useful resources to the researchers and medical doctors for diagnosis, prognosis and therapies of PC by the wet-lab validation.

Blood volume estimation in cardiac surgery - A comparative analysis.

INTRODUCTION: This paper seeks to identify which of three published formulas used for estimating the blood volume of normal human subjects correlates most closely with blood volumes measured in a published study where erythrocyte volume was determined by a method using 51Cr and a nonradioactive dye was used to determine the plasma volume. METHODS: Blood volumes predicted by three published algorithms were compared with blood volume estimates from a study by Retzlaff et al. using the two-tailed Wilcoxon signed rank test and a robust version of the Bland-Altman test. RESULTS: When applied to a sample of normal subjects selected from Mayo Clinic personnel and patients, the Nadler formula correlated more closely with blood volume measured using a radio nucleotide technique than did the Allen formula or one based on a saline haemodilution technique. CONCLUSIONS: The Nadler formula correlated more closely with blood volume measurements derived from Retzlaff's study than the other formulas for estimating blood volume in a population with height and weight distribution more consistent with that seen in North America. It should be used in preference to the Allen formula for estimating blood volume in adult patients currently undergoing cardiac surgical procedures. Saline haemodilution techniques used to measure blood volume require validation against more recently developed nuclear medicine techniques using statistical methods other than regression analysis. Until validated, they should be used with caution for estimating blood volume in adult patients currently undergoing cardiac surgical procedures. If a formula using height, weight and sex is used to estimate blood volume in the context of cardiac surgery, then it must be derived using a much more comprehensive sample of the population to which it is applied than has occurred to date. In particular, it should include broader distributions of height, weight and the presence or absence and type of significant valvular disease.

Automatic bad-pixel mask maker for X-ray pixel detectors with application to serial crystallography.

X-ray crystallography has witnessed a massive development over the past decade, driven by large increases in the intensity and brightness of X-ray sources and enabled by employing high-frame-rate X-ray detectors. The analysis of large data sets is done via automatic algorithms that are vulnerable to imperfections in the detector and noise inherent with the detection process. By improving the model of the behaviour of the detector, data can be analysed more reliably and data storage costs can be significantly reduced. One major requirement is a software mask that identifies defective pixels in diffraction frames. This paper introduces a methodology and program based upon concepts of machine learning, called robust mask maker (RMM), for the generation of bad-pixel masks for large-area X-ray pixel detectors based on modern robust statistics. It is proposed to discriminate normally behaving pixels from abnormal pixels by analysing routine measurements made with and without X-ray illumination. Analysis software typically uses a Bragg peak finder to detect Bragg peaks and an indexing method to detect crystal lattices among those peaks. Without proper masking of the bad pixels, peak finding methods often confuse the abnormal values of bad pixels in a pattern with true Bragg peaks and flag such patterns as useful regardless, leading to storage of enormous uninformative data sets. Also, it is computationally very expensive for indexing methods to search for crystal lattices among false peaks and the solution may be biased. This paper shows how RMM vastly improves peak finders and prevents them from labelling bad pixels as Bragg peaks, by demonstrating its effectiveness on several serial crystallography data sets.

Critical comparison of statistical methods for quantifying variability and uncertainty of microbial responses from experimental data.

Variability and uncertainty are important factors for quantitative microbiological risk assessment (QMRA). In this context, variability refers to inherent sources of variation, whereas uncertainty refers to imprecise knowledge or lack of it. In this work we compare three statistical methods to estimate variability in the kinetic parameters of microbial populations: mixed-effect models, multilevel Bayesian models, and a simplified algebraic method previously suggested. We use two case studies that analyse the influence of three levels of variability: (1) between-strain variability (different strains of the same species), (2) within-strain variability (biologically independent reproductions of the same strain) and, at the most nested level, (3) experimental variability (species independent technical lab variability resulting in uncertainty about the population characteristic of interest) on the growth and inactivation of Listeria monocytogenes. We demonstrate that the algebraic method, although relatively easy to use, overestimates the contribution of between-strain and within-strain variability due to the propagation of experimental variability in the nested experimental design. The magnitude of the bias is proportional to the variance of the lower levels and inversely proportional to the number of repetitions. This bias was very relevant in the case study related to growth, whereas for the case study on inactivation the resulting insights in variability were practically independent of the method used. The mixed-effects model and the multilevel Bayesian models calculate unbiased estimates for all levels of variability in all the cases tested. Consequently, we recommend using the algebraic method for initial screenings due to its simplicity. However, to obtain parameter estimates for QMRA, the more complex methods should generally be used to obtain unbiased estimates.

A unified graph model based on molecular data binning for disease subtyping.

Molecular disease subtype discovery from omics data is an important research problem in precision medicine. The biggest challenges are the skewed distribution and data variability in the measurements of omics data. These challenges complicate the efficient identification of molecular disease subtypes defined by clinical differences, such as survival. Existing approaches adopt kernels to construct patient similarity graphs from each view through pairwise matching. However, the distance functions used in kernels are unable to utilize the potentially critical information of extreme values and data variability which leads to the lack of robustness. In this paper, a novel robust distance metric (ROMDEX) is proposed to construct similarity graphs for molecular disease subtypes from omics data, which is able to address the data variability and extreme values challenges. The proposed approach is validated on multiple TCGA cancer datasets, and the results are compared with multiple baseline disease subtyping methods. The evaluation of results is based on Kaplan-Meier survival time analysis, which is validated using statistical tests e.g, Cox-proportional hazard (Cox p-value). We reject the null hypothesis that the cohorts have the same hazard, for the P-values less than 0.05. The proposed approach achieved best P-values of 0.00181, 0.00171, and 0.00758 for Gene Expression, DNA Methylation, and MicroRNA data respectively, which shows significant difference in survival between the cohorts. In the results, the proposed approach outperformed the existing state-of-the-art (MRGC, PINS, SNF, Consensus Clustering and Icluster+) disease subtyping approaches on various individual disease views of multiple TCGA datasets.