scholarly journals The influence of a priori grouping on inference of genetic clusters: simulation study and literature review of the DAPC method

Heredity ◽  
2020 ◽  
Vol 125 (5) ◽  
pp. 269-280 ◽  
Author(s):  
Joshua M. Miller ◽  
Catherine I. Cullingham ◽  
Rhiannon M. Peery
Keyword(s):  
Discriminant Analysis ◽  
Literature Review ◽  
Simulation Study ◽  
De Novo ◽  
A Priori ◽  
Principal Component ◽  
Migration Rates ◽  
Genetic Clusters ◽  
Genetic Clustering ◽  
Structure Versus

Abstract Inference of genetic clusters is a key aim of population genetics, sparking development of numerous analytical methods. Within these, there is a conceptual divide between finding de novo structure versus assessment of a priori groups. Recently developed, Discriminant Analysis of Principal Components (DAPC), combines discriminant analysis (DA) with principal component (PC) analysis. When applying DAPC, the groups used in the DA (specified a priori or described de novo) need to be carefully assessed. While DAPC has rapidly become a core technique, the sensitivity of the method to misspecification of groups and how it is being empirically applied, are unknown. To address this, we conducted a simulation study examining the influence of a priori versus de novo group designations, and a literature review of how DAPC is being applied. We found that with a priori groupings, distance between genetic clusters reflected underlying FST. However, when migration rates were high and groups were described de novo there was considerable inaccuracy, both in terms of the number of genetic clusters suggested and placement of individuals into those clusters. Nearly all (90.1%) of 224 studies surveyed used DAPC to find de novo clusters, and for the majority (62.5%) the stated goal matched the results. However, most studies (52.3%) omit key run parameters, preventing repeatability and transparency. Therefore, we present recommendations for standard reporting of parameters used in DAPC analyses. The influence of groupings in genetic clustering is not unique to DAPC, and researchers need to consider their goal and which methods will be most appropriate.

Comparison of Principal Component Solutions in Two Populations

Methodology ◽  
2016 ◽  
Vol 12 (1) ◽  
pp. 11-20 ◽  
Author(s):  
Gregor Sočan
Keyword(s):  
Simulation Study ◽  
Principal Components ◽  
Common Factor ◽  
Principal Component ◽  
Component Model ◽  
Bootstrap Procedure ◽  
Factor Loadings ◽  
Component Loadings ◽  
Principal Component Model ◽  
Two Populations

Abstract. When principal component solutions are compared across two groups, a question arises whether the extracted components have the same interpretation in both populations. The problem can be approached by testing null hypotheses stating that the congruence coefficients between pairs of vectors of component loadings are equal to 1. Chan, Leung, Chan, Ho, and Yung (1999) proposed a bootstrap procedure for testing the hypothesis of perfect congruence between vectors of common factor loadings. We demonstrate that the procedure by Chan et al. is both theoretically and empirically inadequate for the application on principal components. We propose a modification of their procedure, which constructs the resampling space according to the characteristics of the principal component model. The results of a simulation study show satisfactory empirical properties of the modified procedure.

Iterative Supervised Principal Component Analysis-Driven Ligand Design for Regioselective Ti-Catalyzed Pyrrole Synthesis

2020 ◽  
Author(s):  
Xin Yi See ◽  
Benjamin Reiner ◽  
Xuelan Wen ◽  
T. Alexander Wheeler ◽  
Channing Klein ◽  
...  
Keyword(s):  
Principal Component Analysis ◽  
De Novo ◽  
Principal Component ◽  
Component Analysis ◽  
Catalyst Design ◽  
Data Driven ◽  
Initial Reaction ◽  
Training Set ◽  
Reaction Conditions ◽  
Component Loadings

<div> <div> <div> <p>Herein, we describe the use of iterative supervised principal component analysis (ISPCA) in de novo catalyst design. The regioselective synthesis of 2,5-dimethyl-1,3,4-triphenyl-1H- pyrrole (C) via Ti- catalyzed formal [2+2+1] cycloaddition of phenyl propyne and azobenzene was targeted as a proof of principle. The initial reaction conditions led to an unselective mixture of all possible pyrrole regioisomers. ISPCA was conducted on a training set of catalysts, and their performance was regressed against the scores from the top three principal components. Component loadings from this PCA space along with k-means clustering were used to inform the design of new test catalysts. The selectivity of a prospective test set was predicted in silico using the ISPCA model, and only optimal candidates were synthesized and tested experimentally. This data-driven predictive-modeling workflow was iterated, and after only three generations the catalytic selectivity was improved from 0.5 (statistical mixture of products) to over 11 (> 90% C) by incorporating 2,6-dimethyl- 4-(pyrrolidin-1-yl)pyridine as a ligand. The successful development of a highly selective catalyst without resorting to long, stochastic screening processes demonstrates the inherent power of ISPCA in de novo catalyst design and should motivate the general use of ISPCA in reaction development. </p> </div> </div> </div>

scholarly journals Inhibition of Kynurenine Metabolism and Its Effect in Mitochondrial Function in Hepatocellular Carcinoma

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 124-125
Author(s):  
Raul Castro-Portuguez ◽  
Samuel Freitas ◽  
George Sutphin
Keyword(s):  
Hepatocellular Carcinoma ◽  
Mitochondrial Function ◽  
De Novo ◽  
Principal Component ◽  
Kynurenine Pathway ◽  
The Cancer Genome Atlas ◽  
Wilcoxon Test ◽  
Nad Synthesis ◽  
Significant Difference ◽  
Kynurenine Metabolism

Abstract Hepatocellular carcinoma (HCC) is the most prevalent cancer in the liver. The majority of ingested tryptophan is processed in the liver through the kynurenine pathway, the endpoint of which is de novo NAD+ biosynthesis. Dysregulation of tryptophan-kynurenine metabolism and NAD+ synthesis may promote mitochondrial malfunction, tumor reprogramming, and carcinogenesis. Using a publicly available gene expression dataset from liver hepatocellular carcinoma (LIHC) samples available through The Cancer Genome Atlas (TCGA; n = 371), we employed Principal Component Analysis (PCA), hierarchical clustering, gene-pattern expression profiling, and survival analysis to cluster patients and determine overall survival. Our analysis of genes encoding kynurenine pathway enzymes determined that patients with high QPRT expression had a poor prognosis with decreased median survival, with no effect on the maximum survival. There is a significant difference in the survival between patients with high QPRT expression relative to patients with high HAAO/AFMID expression (HR = 1.2, [95% CI 0.5-1.8] P = 0.0181, Gehan-Breslow-Wilcoxon Test). Patients with high QPRT expression have higher survival rates compared with low QPRT expression (HR = 1.4, [95% CI 0.9-2.2] P = 0.0344, Gehan-Breslow-Wilcoxon Test). To test the consequences of kynurenine-pathway inhibition in mitochondrial function and morphology we use 4-Cl-3HAA, an irreversible HAAO inhibitor, and observed a small increase in mitochondrial fragmentation in HepG2 cells after 24 hours of treatment. We conclude that kynurenine metabolism may be useful as a biomarker to predict patient prognosis among HCC patients. In ongoing work, we are testing QPRT inhibitors in cell culture as a potential adjuvant for chemotherapies.

scholarly journals A fast and low-cost approach to quality control of alcohol-based hand sanitizer using portable near infrared spectrometer and chemometrics

2021 ◽  
pp. 096703352098731
Author(s):  
Adenilton C da Silva ◽  
Lívia PD Ribeiro ◽  
Ruth MB Vidal ◽  
Wladiana O Matos ◽  
Gisele S Lopes
Keyword(s):  
Quality Control ◽  
Discriminant Analysis ◽  
Near Infrared ◽  
Nir Spectroscopy ◽  
Principal Component ◽  
Partial Least Square ◽  
Least Square ◽  
Chemical Components ◽  
Linear Discriminant ◽  
Hand Sanitizer

The use of alcohol-based hand sanitizers is recommended as one of several strategies to minimize contamination and spread of the COVID-19 disease. Current reports suggest that the virucidal potential of ethanol occurs at concentrations close to 70%. Traditional methods of verifying the ethanol concentration in such products invite potential errors due to the viscosity of chemical components or may be prohibitively expensive to undertake in large demand. Near infrared (NIR) spectroscopy and chemometrics have already been used for the determination of ethanol in other matrices and present an alternative fast and reliable approach to quality control of alcohol-based hand sanitizers. In this study, a portable NIR spectrometer combined with classification chemometric tools, i.e., partial least square discriminant analysis (PLS–DA) and linear discriminant analysis with successive algorithm projection (SPA–LDA) were used to construct models to identify conforming and non-conforming commercial and laboratory synthesized hand sanitizer samples. Principal component analysis (PCA) was applied in an exploratory data study. Three principal components accounted for 99% of data variance and demonstrate clustering of conforming and non-conforming samples. The PLS–DA and SPA–LDA classification models presented 77 and 100% of accuracy in cross/internal validation respectively and 100% of accuracy in the classification of test samples. A total of 43% commercial samples evaluated using the PLS–DA and SPA–LDA presented ethanol content non-conforming for hand sanitizer gel. These results indicate that use of NIR spectroscopy and chemometrics is a promising strategy, yielding a method that is fast, portable, and reliable for discrimination of alcohol-based hand sanitizers with respect to conforming and non-conforming ethanol concentrations.

Array-based characterization of an interstitial de-novo deletion of chromosome 4q in a patient with a neuronal migration defect and hypocalcemia plus a literature review

2012 ◽  
Vol 21 (3) ◽  
pp. 172-176 ◽  
Author(s):  
Marta Moreno-García ◽  
Jaime Sánchez del Pozo ◽  
Jaime Cruz-Rojo ◽  
Francisco Javier Fernández-Martínez ◽  
Guiomar Perez-Nanclares Leal
Keyword(s):  
Literature Review ◽  
Neuronal Migration ◽  
De Novo ◽  
Neuronal Migration Defect

scholarly journals The rare hemoglobin variant Hb Mizuho: report of a Swiss family and literature review

2021 ◽  
Author(s):  
Linet Njue ◽  
Cesare Medri ◽  
Peter Keller ◽  
Miriam Diepold ◽  
Behrouz Mansouri Taleghani ◽  
...  
Keyword(s):  
Literature Review ◽  
Hemolytic Anemia ◽  
De Novo ◽  
Clinical History ◽  
Molecular Techniques ◽  
De Novo Mutation ◽  
First Case ◽  
History Of ◽  
Transfusion Dependency ◽  
Unstable Hemoglobin

AbstractHb Mizuho is a very rare unstable hemoglobin; here, we describe the clinical history of three Swiss family members with Hb Mizuho together with a systematic review of the previously six published cases. The clinical history of the adult woman we report here is unique since this is the first Hb Mizuho presenting with Moyamoya complications and the first case reported with long-term erythrocyte exchange. The literature review showed that Hb Mizuho was mainly reported as a de novo mutation, with the exception of children descended from known cases. All published patients with this unstable hemoglobin showed severe hemolytic anemia with the exception of one; all were regularly transfused. Patients with higher HbF levels might require fewer transfusions. All patients underwent splenectomy at a median age of 4 years and had variable clinical improvement; some achieved complete resolution of transfusion dependency after splenectomy. Iron overload in Hb Mizuho patients seems to be mainly attributed to transfusions and has less to do with ineffective erythropoiesis. Diagnosis might be challenging; a normal hemoglobin electrophoresis should not rule out the diagnosis of unstable hemoglobin in patients with otherwise unexplained hemolytic anemia. This series shows the enormous utility of using molecular techniques for diagnosis.

Identification of two novel de novo TUBB variants in cases with brain malformations: case reports and literature review

2021 ◽  
Author(s):  
Kazuki Watanabe ◽  
Mitsuko Nakashima ◽  
Satoko Kumada ◽  
Hideaki Mashimo ◽  
Mikako Enokizono ◽  
...  
Keyword(s):  
Literature Review ◽  
De Novo ◽  
Case Reports ◽  
Brain Malformations

Identification and Quantification of Metamizole in Traditional Herbal Medicines using Spectroscopy FTIR-ATR combined with Chemometrics

2021 ◽  
pp. 4413-4419
Author(s):  
Dharmastuti Cahya Fatmarahmi ◽  
Ratna Asmah Susidarti ◽  
Respati Tri Swasono ◽  
Abdul Rohman
Keyword(s):  
Discriminant Analysis ◽  
Herbal Medicine ◽  
Ftir Spectroscopy ◽  
Herbal Medicines ◽  
Principal Component ◽  
Attenuated Total Reflection ◽  
Partial Least Square ◽  
Least Square ◽  
Partial Least Square Regression ◽  
Precision Data

The study aims to develop an effective, efficient, and reliable method using Fourier Transform Infrared (FTIR) spectroscopy with Attenuated Total Reflection (ATR) combined with chemometric for identifying the synthetic drug in Indonesian herbal medicine known as Jamu. Jamu powders, Metamizole, and the binary mixture of Jamu and Metamizole were measured using FTIR-ATR at the mid-infrared region (4000-650 cm-1). The obtained spectra profiles were further analyzed by Principal Component Analysis, Partial Least Square Regression, Principal Component Regression, and Discriminant Analysis. Jamu Pegel Linu (JPL), Jamu Encok (JE), Jamu Sakit Pinggang (JSP), Metamizole (M), and adulterated Jamu by Metamizole were discriminated well on PCA score plot. PLSR and PCR showed the accuracy and precision data to quantify JPL, JE, and JSP, and each adulterated by M with R2 value > 0,995 and low value of RMSEC and RMSEP. Discriminant Analysis (DA) was successfully grouping Jamu and Metamizole without any misclassification. A combination of FTIR spectroscopy and chemometrics offered useful tools for detecting Metamizole in traditional herbal medicine.

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