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Óscar Yanes

Universidad Rovira i Virgili

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Co-Authors

Jordi Capellades

Universidad Rovira i Virgili

María Vinaixa

Institut d'Investigació Sanitària Pere Virgili

Miguel Rodríguez

Hospital Universitario Virgen del Rocío

Clyde Bango

Dana-Farber Cancer Institute

Giorgia Zadra

National Research Council

Svitlana Tyekucheva

Dana-Farber Cancer Institute

Massimo Loda

Dana-Farber Cancer Institute

Kathryn L. Penney

Harvard University

Stefano Cacciatore

International Centre for Genetic Engineering and Biotechnology

Sara Samino

Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition

Cooperative Institutions

Instituto de Salud Carlos III

202

Universitat de Barcelona

180

Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas

125

Centro de Investigación Biomédica en Red

116

Universitat Autònoma de Barcelona

Institut d'Investigació Biomédica de Bellvitge

Universidad Rovira i Virgili

Institut d'Investigació Sanitària Pere Virgili

Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition

Consorci Institut D'Investigacions Biomediques August Pi I Sunyer

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Approaches to detect biomolecular interactions by maldi-tof mass spectrometry

Óscar Yanes

En la presente tesis se describen diferentes aproximaciones para detectar complejos no covalentes entre proteinas por espectrometria de masas maldi-tof. Especialmente, aquellas que se dan entre proteasas e inhibidores de proteasas proteicos presentes en muestras biologicas.

MALDI imaging

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MAPI: A Server for Improving Protein Identification from a Four Matrices Mass Spectrometry Approach

Current Proteomics (2010)

Juan Cedano Óscar Yanes Mario Ferrer‐Navarro Sílvia Bronsoms Enrique Querol

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and peptide mass fingerprint (PMF) are one of the most powerful combined tool for protein identification. Frequently it is the method of choice as it is faster and less expensive than protein sequencing. However, sometimes PMF only allows the identification of a subset of peptides, requiring further MS/MS or Edman degradation to attain unequivocal protein identification. This work describes an approach that combines several matrices to improve the fidelity of the protein identification by MALDI-TOF MS. The matrices used for sample preparation are 2,5-dihydroxybenzoic acid (DHB), 2,6- dihydroxyacetophenone (DHAP), CHCA and 2,4,6-Trihydroxy acetophenone (THAP). We have also developed an algorithm called Matrix Assisted Protein Identification (MAPI) that processes Mascot datasets derived from each one of the four matrix preparations, integrating them and achieving a significant improvement in protein identification. Keywords: MALDI-TOF MS, protein identification, 2D-electrophoresis, bioinformatics

Identification

Peptide mass fingerprinting

Edman degradation

Matrix (chemical analysis)

10.2174/157016410791330561

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Table S1 from Metabolic Profiling in Formalin-Fixed and Paraffin-Embedded Prostate Cancer Tissues

Stefano Cacciatore Giorgia Zadra Clyde Bango Kathryn L. Penney Svitlana Tyekucheva

Analysis of the metabolites found and missed in FFPE cell samples categorized by superclass, class, subclass, substituent, physical/chemical properties, and pathways.

Subclass

10.1158/1541-7786.22511398.v1

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Table S3 from Metabolic Profiling in Formalin-Fixed and Paraffin-Embedded Prostate Cancer Tissues

Stefano Cacciatore Giorgia Zadra Clyde Bango Kathryn L. Penney Svitlana Tyekucheva

Analysis of the metabolites present in the frozen cell samples and missed in the supernatant and FF cell samples categorized by superclass, class, subclass, substituent, physical/chemical properties, and pathways.

Profiling (computer programming)

Table (database)

10.1158/1541-7786.22511374.v1

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Antioxidant or neurotrophic factor treatment preserves function in a mouse model of neovascularization-associated oxidative stress

Journal of Clinical Investigation (2009)

Michael I. Dorrell Edith Aguilar Ruth Jacobson Óscar Yanes Ray F. Gariano

In several disease states, abnormal growth of blood vessels is associated with local neuronal degeneration. This is particularly true in ocular diseases such as retinal angiomatous proliferation (RAP) and macular telangiectasia (MacTel), in which, despite the absence of large-scale leakage or hemorrhage, abnormal neovascularization (NV) is associated with local neuronal dysfunction. We describe here a retinal phenotype in mice with dysfunctional receptors for VLDL (Vldlr-/- mice) that closely resembles human retinal diseases in which abnormal intra- and subretinal NV is associated with photoreceptor cell death. Such cell death was evidenced by decreased cone and, to a lesser extent, rod opsin expression and abnormal electroretinograms. Cell death in the region of intraretinal vascular abnormalities was associated with an increased presence of markers associated with oxidative stress. Oral antioxidant supplementation protected against photoreceptor degeneration and preserved retinal function, despite the continued presence of abnormal intra- and subretinal vessels. What we believe to be novel, Müller cell-based, virally mediated delivery of neurotrophic compounds specifically to sites of NV was also neuroprotective. These observations demonstrate that neuronal loss secondary to NV can be prevented by the use of simple antioxidant dietary measures or cell-based delivery of neurotrophic factors, even when the underlying vascular phenotype is not altered.

Electroretinography

Photoreceptor cell

10.1172/jci35977

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Epigenetic loss of the endoplasmic reticulum–associated degradation inhibitor SVIP induces cancer cell metabolic reprogramming

JCI Insight (2019)

Pere Llinàs‐Arias Margalida Rosselló-Tortella Paula López-Serra Montserrat Pérez-Salvia Fernando Setién

The endoplasmic reticulum (ER) of cancer cells needs to adapt to the enhanced proteotoxic stress associated with the accumulation of unfolded, misfolded, and transformation-associated proteins. One way by which tumors thrive in the context of ER stress is by promoting ER-associated degradation (ERAD), although the mechanisms are poorly understood. Here, we show that the small p97/VCP-interacting protein (SVIP), an endogenous inhibitor of ERAD, undergoes DNA hypermethylation–associated silencing in tumorigenesis to achieve this goal. SVIP exhibits tumor suppressor features and its recovery is associated with increased ER stress and growth inhibition. Proteomic and metabolomic analyses show that cancer cells with epigenetic loss of SVIP are depleted in mitochondrial enzymes and oxidative respiration activity. This phenotype is reverted upon SVIP restoration. The dependence of SVIP-hypermethylated cancer cells on aerobic glycolysis and glucose was also associated with sensitivity to an inhibitor of the glucose transporter GLUT1. This could be relevant to the management of tumors carrying SVIP epigenetic loss, because these occur in high-risk patients who manifest poor clinical outcomes. Overall, our study provides insights into how epigenetics helps deal with ER stress and how SVIP epigenetic loss in cancer may be amenable to therapies that target glucose transporters.

Endoplasmic-reticulum-associated protein degradation

Reprogramming

10.1172/jci.insight.125888

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Supplementary Figure 8 from Adaptation to HIF1α Deletion in Hypoxic Cancer Cells by Upregulation of GLUT14 and Creatine Metabolism

Alessandro Valli Matteo Morotti Christos E. Zois Patrick K. Albers Tomoyoshi Soga

S8. Hydrophilic metabolites detection and identification performed by LC/MS QTOF nanoflow using AMRT comparison.

Creatine

Identification

Metabolic adaptation

10.1158/1541-7786.22515489.v1

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Enriquecimiento mediante vías metabólicas de datos de Cromatografía Líquida- Espectrometría de Masas a través de análisis espectral de grafos

Sergio Picart‐Armada Francesc Fernández-Albert M. Rosario Huesa Vinaixa Óscar Yanes Alexandre Perera-Lluna

Una de las tecnicas experimentales mas extendidas en el ambito de investigacion biologica y la quimica analitica es la Cromatografia Liquida – Espectrometria de Masas, CL/EM, cuya salida informa sobre los compuestos presentes en las muestras mediante una tecnica de separacion fisica acoplada a una separacion en funcion de la relacion carga-masa. Las tecnicas de enriquecimiento de vias metabolicas son preciadas en el tratamiento de conjuntos extensivos de datos, puesto que traducen esta informacion sobre computestos en terminos de vias metabolicas a la vez que reducen el ruido estadistico. Las vias metabolicas son fuente de conocimiento por su estrecha relacion con los mecanismos biologicos. Este trabajo propone una nueva tecnica de enriquecimiento de datos obtenidos en CL/EM mediante una estrategia en dos bloques. El primero consiste en plasmar la base de datos Kyoto Encyclopedia of Genes and Genomes en grafos interpretables. El segundo trata de aplicar algoritmos de difusion de calor y PageRank sobre dichos grafos, con el objetivo de llevar a termino el enriquecimiento. Estos procedimientos se han aplicado en un caso real y sus resultados coinciden con los de validacion funcional.

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Lipoprotein hydrophobic core lipids are partially extruded to surface in smaller HDL: “Herniated” HDL, a common feature in diabetes

Scientific Reports (2016)

Núria Amigó Roger Mallol Mercedes Heras Sergio Martínez‐Hervás Francisco Blanco‐Vaca

Abstract Recent studies have shown that pharmacological increases in HDL cholesterol concentrations do not necessarily translate into clinical benefits for patients, raising concerns about its predictive value for cardiovascular events. Here we hypothesize that the size-modulated lipid distribution within HDL particles is compromised in metabolic disorders that have abnormal HDL particle sizes, such as type 2 diabetes mellitus (DM2). By using NMR spectroscopy combined with a biochemical volumetric model we determined the size and spatial lipid distribution of HDL subclasses in a cohort of 26 controls and 29 DM2 patients before and after two drug treatments, one with niacin plus laropiprant and another with fenofibrate as an add-on to simvastatin. We further characterized the HDL surface properties using atomic force microscopy and fluorescent probes to show an abnormal lipid distribution within smaller HDL particles, a subclass particularly enriched in the DM2 patients. The reduction in the size, force cholesterol esters and triglycerides to emerge from the HDL core to the surface, making the outer surface of HDL more hydrophobic. Interestingly, pharmacological interventions had no effect on this undesired configuration, which may explain the lack of clinical benefits in DM2 subjects.

Fenofibrate

Niacin

10.1038/srep19249

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Citations (31)

Mass Spectrometry Data Processing

Chapman and Hall/CRC eBooks (2019)

Steffen Neumann Óscar Yanes Roland Mumm Pietro Franceschi

This chapter focuses on the mass spectrometry data processing workflow. The first step consists of processing the raw MS data, leading to a feature matrix amenable for statistical analysis. The raw MS files contain the list of spectra acquired during the run, and each spectrum contains many pairs. In the field of metabolite fingerprinting, Direct Infusion Mass Spectrometry and Flow Injection Mass Spectrometry can be used to complement chromatography-based MS techniques. To reduce this complexity, several feature detection algorithms have been developed. A feature is characterized by a retention time, an m/z value and an intensity. In microarray data analysis it is relatively straightforward to compare the expression of some genes in one sample against the expression in a second one, because the RNA is hybridized to a particular "known" probe sequence. In case an accurate-mass spectrometer has been used, it is also important to determine the mass accuracy in the measurements.

10.1201/9781315370583-4

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