22 research outputs found
Evaluation of multiple variate selection methods from a biological perspective: a nutrigenomics case study
Genomics-based technologies produce large amounts of data. To interpret the results and identify the most important variates related to phenotypes of interest, various multivariate regression and variate selection methods are used. Although inspected for statistical performance, the relevance of multivariate models in interpreting biological data sets often remains elusive. We compare various multivariate regression and variate selection methods applied to a nutrigenomics data set in terms of performance, utility and biological interpretability. The studied data set comprised hepatic transcriptome (10,072 predictor variates) and plasma protein concentrations [2 dependent variates: Leptin (LEP) and Tissue inhibitor of metalloproteinase 1 (TIMP-1)] collected during a high-fat diet study in ApoE3Leiden mice. The multivariate regression methods used were: partial least squares “PLS”; a genetic algorithm-based multiple linear regression, “GA-MLR”; two least-angle shrinkage methods, “LASSO” and “ELASTIC NET”; and a variant of PLS that uses covariance-based variate selection, “CovProc.” Two methods of ranking the genes for Gene Set Enrichment Analysis (GSEA) were also investigated: either by their correlation with the protein data or by the stability of the PLS regression coefficients. The regression methods performed similarly, with CovProc and GA performing the best and worst, respectively (R-squared values based on “double cross-validation” predictions of 0.762 and 0.451 for LEP; and 0.701 and 0.482 for TIMP-1). CovProc, LASSO and ELASTIC NET all produced parsimonious regression models and consistently identified small subsets of variates, with high commonality between the methods. Comparison of the gene ranking approaches found a high degree of agreement, with PLS-based ranking finding fewer significant gene sets. We recommend the use of CovProc for variate selection, in tandem with univariate methods, and the use of correlation-based ranking for GSEA-like pathway analysis methods
Identification of a Binding Site for Unsaturated Fatty Acids in the Orphan Nuclear Receptor Nurr1
Nurr1/NR4A2 is an orphan nuclear
receptor, and currently there
are no known natural ligands that bind Nurr1. A recent metabolomics
study identified unsaturated fatty acids, including arachidonic acid
and docosahexaenoic acid (DHA), that interact with the ligand-binding
domain (LBD) of a related orphan receptor, Nur77/NR4A1. However, the
binding location and whether these ligands bind other NR4A receptors
were not defined. Here, we show that unsaturated fatty acids also
interact with the Nurr1 LBD, and solution NMR spectroscopy reveals
the binding epitope of DHA at its putative ligand-binding pocket.
Biochemical assays reveal that DHA-bound Nurr1 interacts with high
affinity with a peptide derived from PIASγ, a protein that interacts
with Nurr1 in cellular extracts, and DHA also affects cellular Nurr1
transactivation. This work is the first structural report of a natural
ligand binding to a canonical NR4A ligand-binding pocket and indicates
a natural ligand can bind and affect Nurr1 function
Recommended from our members
International Union of Basic and Clinical Pharmacology CXIII: Nuclear Receptor Superfamily - Update 2023
FULL Investiga N°2
Contiene: Educación en competencias socio emocionales: una transformación escolar necesaria para las infancias / Lupe García Cano, Soledad Niño Murcia -- Economía Informal: la otra cara de la pandemia COVID-19 / Sandra Patricia Bohórquez Pacheco, Melva Inés Gómez Caicedo -- Valoración crítica de manuales de investigación contable: entre la orientación y la prescripción / Mateo Bedoya García, Andrés Cabrera Narváez, Fabián Leonardo Quinche Martín -- Formación docente en Colombia: una cuestión de calidad educativa / Juan Carlos Mariño Mendoza -- Didácticas y estrategias para el aprendizaje virtual del diseño / Nidia Raquel Gualdrón Cantor -- Panorama del sector turístico: tema de reflexión académica en el año 2020 / Ana Milena Luengas Alarcón -- Realidad Virtual bajo una visión modular de Industria 4.0 / Juan P. Navarro Londoño, Luis E. Vallejo Sánchez -- El poder de la voz para el control de las enfermedades crónicas / María Carolina Niño Rivera -- La ilustración gráfica aplicada al campo médico / Elena Patricia Ramírez Agudelo, Armando Armando -- Iglesia, prensa y anticlericalismo: escenarios del proyecto modernizador en la Colombia de mediados del siglo XIX / Roberto Herrera Cañón -- Reflexiones sobre la Ilustración gráfica en Colombia: la ilustración en la literatura infantil como otra manera de escribir / Juliet Daniela Galindo Zuleta, Edison Javier Mora González -- El ecosistema de emprendimiento en Bogotá, incipiente, pero en crecimiento / Yurian Adriana Bustamante Reyes, Danna Mitchelle Mejía Villarruel, Maicol Esneider Novoa González -- Intervención estatal: ¿contribuye o retarda el desarrollo económico? / María Fernanda León Castillo.Fundación Universitaria Los Libertadore