Principal component analysis (PCA) has been widely used to visualize high-dimensional metabolomic data in a two- or three-dimensional subspace. In metabolomics, some metabolites (e.g., the top 10 metabolites) have been subjectively selected when using factor loading in PCA, and biological inferences are made for these metabolites. However, this approach may lead to biased biological inferences because these metabolites are not objectively selected with statistical criteria.

The dry root and rhizome of Ligusticum chuanxiong Hort., or Chuanxiong, has been used as a blood-activating and stasis-removing traditional Chinese medicine for 1000 years. Our previous studies have shown the inhibitory activity on platelet and thrombin (THR) of Chuanxiong. THR and factor Xa (FXa) play significant roles in the coagulation cascade and their inhibitors are of valuable in the treatment of thromboembolic diseases. The aim of the present study is to screen THR and FXa inhibitors from Chuanxiong.

The aim of this study was to investigate the expression of cyclin-dependent kinase 1 (CDK1) in gastric cancer (GC), evaluate its relationship with the clinicopathological features and prognosis of GC, and analyze the advantage of CDK1 as a potential independent prognostic factor for GC.

Statistical coupling analysis (SCA) is a method for analyzing multiple sequence alignments that was used to identify groups of coevolving residues termed "sectors". The method applies spectral analysis to a matrix obtained by combining correlation information with sequence conservation. It has been asserted that the protein sectors identified by SCA are functionally significant, with different sectors controlling different biochemical properties of the protein. Here we reconsider the available experimental data and note that it involves almost exclusively proteins with a single sector. We show that in this case sequence conservation is the dominating factor in SCA, and can alone be used to make statistically equivalent functional predictions. Therefore, we suggest shifting the experimental focus to proteins for which SCA identifies several sectors. Correlations in protein alignments, which have been shown to be informative in a number of independent studies, would then be less dominated by sequence conservation.

The dry root and rhizome of Salvia miltiorrhiza Bunge, or Danshen, is a well-known traditional Chinese medicine with anticoagulant activity. Taking into account that thrombin (THR) and factor Xa (FXa) play crucial roles in the coagulation cascade, it is reasonable and meaningful to screening THR and/or FXa inhibitors from Danshen.

The biochemical half maximal inhibitory concentration (IC50) is the most commonly used metric for on-target activity in lead optimization. It is used to guide lead optimization, build large-scale chemogenomics analysis, off-target activity and toxicity models based on public data. However, the use of public biochemical IC50 data is problematic, because they are assay specific and comparable only under certain conditions. For large scale analysis it is not feasible to check each data entry manually and it is very tempting to mix all available IC50 values from public database even if assay information is not reported. As previously reported for Ki database analysis, we first analyzed the types of errors, the redundancy and the variability that can be found in ChEMBL IC50 database. For assessing the variability of IC50 data independently measured in two different labs at least ten IC50 data for identical protein-ligand systems against the same target were searched in ChEMBL. As a not sufficient number of cases of this type are available, the variability of IC50 data was assessed by comparing all pairs of independent IC50 measurements on identical protein-ligand systems. The standard deviation of IC50 data is only 25% larger than the standard deviation of Ki data, suggesting that mixing IC50 data from different assays, even not knowing assay conditions details, only adds a moderate amount of noise to the overall data. The standard deviation of public ChEMBL IC50 data, as expected, resulted greater than the standard deviation of in-house intra-laboratory/inter-day IC50 data. Augmenting mixed public IC50 data by public Ki data does not deteriorate the quality of the mixed IC50 data, if the Ki is corrected by an offset. For a broad dataset such as ChEMBL database a Ki- IC50 conversion factor of 2 was found to be the most reasonable.

Recently developed techniques to visualize immunostained tissues in 3D and in large samples have expanded the scope of microscopic investigations at the level of the whole brain. Here, we propose to adapt voxel-based statistical analysis to 3D high-resolution images of the immunostained rodent brain. The proposed approach was first validated with a simulation dataset with known cluster locations. Then, it was applied to characterize the effect of ADAM30, a gene involved in the metabolism of the amyloid precursor protein, in a mouse model of Alzheimer's disease. This work introduces voxel-based analysis of 3D immunostained microscopic brain images and, therefore, opens the door to localized whole-brain exploratory investigation of pathological markers and cellular alterations.

Dietary pattern analysis is a promising approach to understanding the complex relationship between diet and health. While many statistical methods exist, the literature predominantly focuses on classical methods such as dietary quality scores, principal component analysis, factor analysis, clustering analysis, and reduced rank regression. There are some emerging methods that have rarely or never been reviewed or discussed adequately.

The Indus script is one of the major undeciphered scripts of the ancient world. The small size of the corpus, the absence of bilingual texts, and the lack of definite knowledge of the underlying language has frustrated efforts at decipherment since the discovery of the remains of the Indus civilization. Building on previous statistical approaches, we apply the tools of statistical language processing, specifically n-gram Markov chains, to analyze the syntax of the Indus script. We find that unigrams follow a Zipf-Mandelbrot distribution. Text beginner and ender distributions are unequal, providing internal evidence for syntax. We see clear evidence of strong bigram correlations and extract significant pairs and triplets using a log-likelihood measure of association. Highly frequent pairs and triplets are not always highly significant. The model performance is evaluated using information-theoretic measures and cross-validation. The model can restore doubtfully read texts with an accuracy of about 75%. We find that a quadrigram Markov chain saturates information theoretic measures against a held-out corpus. Our work forms the basis for the development of a stochastic grammar which may be used to explore the syntax of the Indus script in greater detail.

In this paper, the first version of the software SEDA (SEDAv1.0), designed to help seismologists statistically analyze earthquake data, is presented. The package consists of a user-friendly Matlab-based interface, which allows the user to easily interact with the application, and a computational core of Fortran codes, to guarantee the maximum speed. The primary factor driving the development of SEDA is to guarantee the research reproducibility, which is a growing movement among scientists and highly recommended by the most important scientific journals. SEDAv1.0 is mainly devoted to produce accurate and fast outputs. Less care has been taken for the graphic appeal, which will be improved in the future. The main part of SEDAv1.0 is devoted to the ETAS modeling. SEDAv1.0 contains a set of consistent tools on ETAS, allowing the estimation of parameters, the testing of model on data, the simulation of catalogs, the identification of sequences and forecasts calculation. The peculiarities of routines inside SEDAv1.0 are discussed in this paper. More specific details on the software are presented in the manual accompanying the program package.

The current literature establishes the importance of gene functional category and expression in promoting or suppressing duplicate gene loss after whole genome doubling in plants, a process known as fractionation. Inspired by studies that have reported gene expression to be the dominating factor in preventing duplicate gene loss, we analyzed the relative effect of functional category and expression.

We report an approach to predict DNA specificity of the tetracycline repressor (TetR) family transcription regulators (TFRs). First, a genome sequence-based method was streamlined with quantitative P-values defined to filter out reliable predictions. Then, a framework was introduced to incorporate structural data and to train a statistical energy function to score the pairing between TFR and TFR binding site (TFBS) based on sequences. The predictions benchmarked against experiments, TFBSs for 29 out of 30 TFRs were correctly predicted by either the genome sequence-based or the statistical energy-based method. Using P-values or Z-scores as indicators, we estimate that 59.6% of TFRs are covered with relatively reliable predictions by at least one of the two methods, while only 28.7% are covered by the genome sequence-based method alone. Our approach predicts a large number of new TFBs which cannot be correctly retrieved from public databases such as FootprintDB. High-throughput experimental assays suggest that the statistical energy can model the TFBSs of a significant number of TFRs reliably. Thus the energy function may be applied to explore for new TFBSs in respective genomes. It is possible to extend our approach to other transcriptional factor families with sufficient structural information.

Colorectal cancer (CRC) is considered a major global health concern due to an increasing number of new cases and cancer-related deaths each year, strong link to dietary habits prevalent in middle and high-income countries and limited therapeutic options especially in locally-advanced and metastatic settings. To counter this growing problem, the scientific community has strived to underpin the major molecular mechanisms behind the aggressive phenotype displayed by CRC and also develop new agents to selectively target and inhibit these core drivers. This evolution has allowed the separation of patients according to different risk groups in concordance with epidemiological parameters alongside novel biomarkers such as gene alterations, protein overexpression and aberrant signaling pathways. In this study we included 20 patients who underwent colonoscopy and were later received histopathologic confirmation of CRC. The statistical anamnestic data obtained from the patients (age, gender, home distribution, signs and symptoms) was corroborated with the results obtained from the histopathologic and immunohistochemical analysis of the samples obtained via colonoscopy. The average age was 63.8 years, the male: female ratio was 2.33 and the origin of 2/3 of the patients was urban and the most encountered symptoms were transit disorders (75%). In terms of colonoscopy results, the majority of tumors were found on the rectum (85%), 90% of tumors were adenocarcinomas, having a vegetant aspect in 60% of the cases and a moderate degree of differentiation in 50% of situations.

Microbiome studies have become routine in biomedical, agricultural and environmental sciences with diverse aims, including diversity profiling, functional characterization, and translational applications. The resulting complex, often multi-omics datasets demand powerful, yet user-friendly bioinformatics tools to reveal key patterns, important biomarkers, and potential activities. Here we introduce MicrobiomeAnalyst 2.0 to support comprehensive statistics, visualization, functional interpretation, and integrative analysis of data outputs commonly generated from microbiome studies. Compared to the previous version, MicrobiomeAnalyst 2.0 features three new modules: (i) a Raw Data Processing module for amplicon data processing and taxonomy annotation that connects directly with the Marker Data Profiling module for downstream statistical analysis; (ii) a Microbiome Metabolomics Profiling module to help dissect associations between community compositions and metabolic activities through joint analysis of paired microbiome and metabolomics datasets; and (iii) a Statistical Meta-Analysis module to help identify consistent signatures by integrating datasets across multiple studies. Other important improvements include added support for multi-factor differential analysis and interactive visualizations for popular graphical outputs, updated methods for functional prediction and correlation analysis, and expanded taxon set libraries based on the latest literature. These new features are demonstrated using a multi-omics dataset from a recent type 1 diabetes study. MicrobiomeAnalyst 2.0 is freely available at microbiomeanalyst.ca.

ChIP-exo/nexus experiments rely on innovative modifications of the commonly used ChIP-seq protocol for high resolution mapping of transcription factor binding sites. Although many aspects of the ChIP-exo data analysis are similar to those of ChIP-seq, these high throughput experiments pose a number of unique quality control and analysis challenges. We develop a novel statistical quality control pipeline and accompanying R/Bioconductor package, ChIPexoQual, to enable exploration and analysis of ChIP-exo and related experiments. ChIPexoQual evaluates a number of key issues including strand imbalance, library complexity, and signal enrichment of data. Assessment of these features are facilitated through diagnostic plots and summary statistics computed over regions of the genome with varying levels of coverage. We evaluated our QC pipeline with both large collections of public ChIP-exo/nexus data and multiple, new ChIP-exo datasets from Escherichia coli. ChIPexoQual analysis of these datasets resulted in guidelines for using these QC metrics across a wide range of sequencing depths and provided further insights for modelling ChIP-exo data.

The current versions of reference genome assemblies still contain gaps represented by stretches of Ns. Since high throughput sequencing reads cannot be mapped to those gap regions, the regions are depleted of experimental data. Moreover, several technology platforms assay a targeted portion of the genomic sequence, meaning that regions from the unassayed portion of the genomic sequence cannot be detected in those experiments. We here refer to all such regions as inaccessible regions, and hypothesize that ignoring these regions in the null model may increase false findings in statistical testing of colocalization of genomic features.

Investigating organ biology often requires methodologies to induce genetically distinct clones within a living tissue. However, the 3D nature of clones makes sample image analysis challenging and slow, limiting the amount of information that can be extracted manually. Here we develop PECAn, a pipeline for image processing and statistical data analysis of complex multi-genotype 3D images. PECAn includes data handling, machine-learning-enabled segmentation, multivariant statistical analysis, and graph generation. This enables researchers to perform rigorous analyses rapidly and at scale, without requiring programming skills. We demonstrate the power of this pipeline by applying it to the study of Minute cell competition. We find an unappreciated sexual dimorphism in Minute cell growth in competing wing discs and identify, by statistical regression analysis, tissue parameters that model and correlate with competitive death. Furthermore, using PECAn, we identify several genes with a role in cell competition by conducting an RNAi-based screen.

We have fabricated a model system of precisely layer-engineered inorganic-organic thin-film structures using atomic/molecular-layer deposition (ALD/MLD). The samples consist of nanoscale polycrystalline ZnO layers and intervening benzene layers, covering a broad range of layer sequences. The samples characterized in this study combined with previous publications provide an excellent sample set to examine thermal transport properties in inorganic-organic thin films. The cross-plane thermal conductivity is found to depend on multiple factors, with the inorganic-organic interface density being the dominating factor. Our work highlights the remarkable capability of interface engineering in suppressing the thermal conductivity of hybrid inorganic-organic materials, e.g., for thermoelectric applications.

The willingness of healthcare workers (HCW) to respond is an important factor in the health system's response capacity during emergencies. Although much research has been devoted to exploring this issue, the statistical methods employed have been predominantly traditional and have not enabled in-depth analysis focused on absenteeism-prone employees during emergencies. The present study employs an innovative statistical approach for modeling HCWs' willingness to respond (WTR) following an earthquake.

Neuroscience has recently made much progress, expanding the complexity of both neural activity measurements and brain-computational models. However, we lack robust methods for connecting theory and experiment by evaluating our new big models with our new big data. Here, we introduce new inference methods enabling researchers to evaluate and compare models based on the accuracy of their predictions of representational geometries: A good model should accurately predict the distances among the neural population representations (e.g. of a set of stimuli). Our inference methods combine novel 2-factor extensions of crossvalidation (to prevent overfitting to either subjects or conditions from inflating our estimates of model accuracy) and bootstrapping (to enable inferential model comparison with simultaneous generalization to both new subjects and new conditions). We validate the inference methods on data where the ground-truth model is known, by simulating data with deep neural networks and by resampling of calcium-imaging and functional MRI data. Results demonstrate that the methods are valid and conclusions generalize correctly. These data analysis methods are available in an open-source Python toolbox (rsatoolbox.readthedocs.io).