Generally, cancer stem cells have epithelial-to-mesenchymal-transition characteristics and other aggressive properties that cause metastasis. However, there have been no confident markers for the ...identification of cancer stem cells and comparative methods examining adherent and sphere cells are widely used to investigate mechanism underlying cancer stem cells, because sphere cells have been known to maintain cancer stem cell characteristics. In this study, we conducted a meta-analysis that combined gene expression profiles from several studies that utilized tumorsphere technology to investigate tumor stem-like breast cancer cells. We used our own gene expression profiles along with the three different gene expression profiles from the Gene Expression Omnibus, which we combined using the ComBat method, and obtained significant gene sets using the gene set analysis of our datasets and the combined dataset. This experiment focused on four gene sets such as cytokine-cytokine receptor interaction that demonstrated significance in both datasets. Our observations demonstrated that among the genes of four significant gene sets, six genes were consistently up-regulated and satisfied the p-value of < 0.05, and our network analysis showed high connectivity in five genes. From these results, we established CXCR4, CXCL1 and HMGCS1, the intersecting genes of the datasets with high connectivity and p-value of < 0.05, as significant genes in the identification of cancer stem cells. Additional experiment using quantitative reverse transcription-polymerase chain reaction showed significant up-regulation in MCF-7 derived sphere cells and confirmed the importance of these three genes. Taken together, using meta-analysis that combines gene set and network analysis, we suggested CXCR4, CXCL1 and HMGCS1 as candidates involved in tumor stem-like breast cancer cells. Distinct from other meta-analysis, by using gene set analysis, we selected possible markers which can explain the biological mechanisms and suggested network analysis as an additional criterion for selecting candidates.
Introducing novel biomarkers for accurately detecting and differentiating rheumatoid arthritis (RA) and osteoarthritis (OA) using clinical samples is essential. In the current study, we searched for ...a novel data-driven gene signature of synovial tissues to differentiate RA from OA patients. Fifty-three RA, 41 OA, and 25 normal microarray-based transcriptome samples were utilized. The area under the curve random forests (RF) variable importance measurement was applied to seek the most influential differential genes between RA and OA. Five algorithms including RF, k-nearest neighbors (kNN), support vector machines (SVM), naïve-Bayes, and a tree-based method were employed for the classification. We found a 16-gene signature that could effectively differentiate RA from OA, including
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. The externally validated accuracy of the RF model was 0.96 (sensitivity = 1.00, specificity = 0.90). Likewise, the accuracy of kNN, SVM, naïve-Bayes, and decision tree was 0.96, 0.96, 0.96, and 0.91, respectively. Functional meta-analysis exhibited the differential pathological processes of RA and OA; suggested promising targets for further mechanistic and therapeutic studies. In conclusion, the proposed genetic signature combined with sophisticated classification methods may improve the diagnosis and management of RA patients.
•Development of an algorithm for fused lasso logistic regression (FLLR) model.•We applied FLLR to classify Alzheimer disease (AD) subjects from normal controls.•We built a classifier based on corpus ...callosum (CC) thickness profiles.•Classifier accuracy was estimated to be 84% based on five-fold cross-validation.•Regions in the genu and splenium differentiated between groups were identified.
We propose a fused lasso logistic regression to analyze callosal thickness profiles. The fused lasso regression imposes penalties on both the l1-norm of the model coefficients and their successive differences, and finds only a small number of non-zero coefficients which are locally constant. An iterative method of solving logistic regression with fused lasso regularization is proposed to make this a practical procedure. In this study we analyzed callosal thickness profiles sampled at 100 equal intervals between the rostrum and the splenium. The method was applied to corpora callosa of elderly normal controls (NCs) and patients with very mild or mild Alzheimer's disease (AD) from the Open Access Series of Imaging Studies (OASIS) database. We found specific locations in the genu and splenium of AD patients that are proportionally thinner than those of NCs. Callosal thickness in these regions combined with the Mini Mental State Examination scores differentiated AD from NC with 84% accuracy.
Chemical profiles of medicinal plants could be dissimilar depending on the cultivation environments, which may influence their therapeutic efficacy. Accordingly, the regional origin of the medicinal ...plants should be authenticated for correct evaluation of their medicinal and market values. Metabolomics has been found very useful for discriminating the origin of many plants. Choosing the adequate analytical tool can be an essential procedure because different chemical profiles with different detection ranges will be produced according to the choice. In this study, four analytical tools, Fourier transform near‑infrared spectroscopy (FT-NIR), 1H-nuclear magnetic resonance spectroscopy (1H‑NMR), liquid chromatography-mass spectrometry (LC-MS), and gas chromatography-mass spectroscopy (GC-MS) were applied in parallel to the same samples of two popular medicinal plants (Gastrodia elata and Rehmannia glutinosa) cultivated either in Korea or China. The classification abilities of four discriminant models for each plant were evaluated based on the misclassification rate and Q2 obtained from principal component analysis (PCA) and orthogonal projection to latent structures-discriminant analysis (OPLS‑DA), respectively. 1H-NMR and LC-MS, which were the best techniques for G. elata and R. glutinosa, respectively, were generally preferable for origin discrimination over the others. Reasoned by integrating all the results, 1H-NMR is the most prominent technique for discriminating the origins of two plants. Nonetheless, this study suggests that preliminary screening is essential to determine the most suitable analytical tool and statistical method, which will ensure the dependability of metabolomics-based discrimination.
Many extensions of the multivariate normal distribution to heavy-tailed distributions are proposed in the literature, which includes scale Gaussian mixture distribution, elliptical distribution, ...generalized elliptical distribution and transelliptical distribution. The inferences for each family of distributions are well studied. However, extensions are overlapped or similar to each other, and it is hard to differentiate one extension from the other. For this reason, in practice, researchers simply pick one of many extensions and apply it to the analysis. In this paper, to enlighten practitioners who should conduct statistical procedures not based on their preferences but based on how data look like, we comparatively review various extensions and their estimators. Also, we fully investigate the inclusion and exclusion relations of different extensions by Venn diagrams and examples. Moreover, in the numerical study, we illustrate visual differences of the extensions by bivariate plots and analyze different scatter matrix estimators based on the microarray data.
This work is motivated by the recent Korean Middle East respiratory syndrome outbreak. We propose an easy online estimation procedure for the case fatality rate, ie, the proportion of deaths among ...the total cases during the course of an epidemic disease, which is an important indicator of the severity of a disease. The key step in our procedure is representing the data with the run‐off triangle, which simultaneously takes into account two time axes, namely, the calendar and disease‐duration times. We restructure the original data into run‐off triangle data, where the cells contain the numbers of cured patients, deceased patients, and patients still having the disease at a given combination of calendar and disease‐duration times. Based on the restructured run‐off triangle data, we propose an online estimator of the case fatality rate. We numerically show the advantages of the proposed estimator compared to the existing estimators in the literature. Finally, we apply our procedure to the 2015 Korean Middle East respiratory syndrome outbreak data.
Quantitative evidence of the metabolic and cardiovascular effects of apples (
) is lacking in interventional studies. This study aimed to summarize the available evidence of the beneficial effects of ...apples and apple-derived products (ADPs) on metabolic and cardiovascular markers.
Peer-reviewed randomized controlled trials (RCTs) were identified from four databases on May 3, 2021 and regularly updated until the end of May 2021. Demographic characteristics, intervention types, and evaluation parameters were extracted. A meta-analysis on the mean difference of change scores was conducted on commonly presented outcomes in the RCTs.
The metabolic and cardiovascular effects of diverse regimens, including whole apple, apple extract, and apple juice, were examined in 18 eligible RCTs. Nine common evaluation outcomes were eventually introduced to the meta-analysis, including total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride, glucose, insulin, C-reactive protein, and systolic/diastolic blood pressures. The levels of TC (-2.69 mg/dL; 95% CI: -5.43, 0.04 mg/dL) and LDL (-2.80 mg/dL; 95% CI: -5.78, 0.17 mg/dL) showed a non-significant decreasing tendency after at least a week of apple consumption. Further subgroup analysis, particularly, a comparison with placebo as a control, showed a significant reduction in TC and LDL levels. When stratified by the baseline level, subjects with high TC and LDL level were shown to have more benefits from the apple intake. Intriguingly, apple and ADPs significantly reduced HDL levels to a small extent (-1.04 mg/dL; 95% CI: -1.79, -0.29 mg/dL). The other markers were mostly unaffected by the intervention.
Our investigation revealed that apples could improve blood cholesterol levels.
https://www.crd.york.ac.uk/prospero/, identifier CRD42020215977.
본 연구에서는 이표본 구간 자료의 확률적 순서 검정 절차를 제안한다. 제안하는 검정 통계량은 U-통계량에 해당하며 본 연구에서는 이에 대한 점근적 분포를 귀무 가설 하에서 유도하였다. 실제 자료와 모의 실험을 통해 새로 제안한 방법의 성능을 단측 이변량 Kolmogorov-Smirnov 검정법과 비교한다.
We construct a procedure to ...test the stochastic order of two samples of interval-valued data. We propose a test statistic that belongs to a U-statistic and derive its asymptotic distribution under the null hypoth- esis. We compare the performance of the newly proposed method with the existing one-sided bivariate Kolmogorov-Smirnov test using real data and simulated data.
Based on the process of carcinogenesis, carcinogens are classified as either genotoxic or non-genotoxic. In contrast to non-genotoxic carcinogens, many genotoxic carcinogens have been reported to ...cause tumor in carcinogenic bioassays in animals. Thus evaluating the genotoxicity potential of chemicals is important to discriminate genotoxic from non-genotoxic carcinogens for health care and pharmaceutical industry safety. Additionally, investigating the difference between the mechanisms of genotoxic and non-genotoxic carcinogens could provide the foundation for a mechanism-based classification for unknown compounds. In this study, we investigated the gene expression of HepG2 cells treated with genotoxic or non-genotoxic carcinogens and compared their mechanisms of action. To enhance our understanding of the differences in the mechanisms of genotoxic and non-genotoxic carcinogens, we implemented a gene set analysis using 12 compounds for the training set (12, 24, 48 h) and validated significant gene sets using 22 compounds for the test set (24, 48 h). For a direct biological translation, we conducted a gene set analysis using Globaltest and selected significant gene sets. To validate the results, training and test compounds were predicted by the significant gene sets using a prediction analysis for microarrays (PAM). Finally, we obtained 6 gene sets, including sets enriched for genes involved in the adherens junction, bladder cancer, p53 signaling pathway, pathways in cancer, peroxisome and RNA degradation. Among the 6 gene sets, the bladder cancer and p53 signaling pathway sets were significant at 12, 24 and 48 h. We also found that the DDB2, RRM2B and GADD45A, genes related to the repair and damage prevention of DNA, were consistently up-regulated for genotoxic carcinogens. Our results suggest that a gene set analysis could provide a robust tool in the investigation of the different mechanisms of genotoxic and non-genotoxic carcinogens and construct a more detailed understanding of the perturbation of significant pathways.
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