@article {710, title = {Transcriptomic Analysis of a Diabetic Skin-Humanized Mouse Model Dissects Molecular Pathways Underlying the Delayed Wound Healing Response.}, journal = {Genes (Basel)}, volume = {12}, year = {2020}, month = {2020 12 31}, abstract = {

Defective healing leading to cutaneous ulcer formation is one of the most feared complications of diabetes due to its consequences on patients{\textquoteright} quality of life and on the healthcare system. A more in-depth analysis of the underlying molecular pathophysiology is required to develop effective healing-promoting therapies for those patients. Major architectural and functional differences with human epidermis limit extrapolation of results coming from rodents and other small mammal-healing models. Therefore, the search for reliable humanized models has become mandatory. Previously, we developed a diabetes-induced delayed humanized wound healing model that faithfully recapitulated the major histological features of such skin repair-deficient condition. Herein, we present the results of a transcriptomic and functional enrichment analysis followed by a mechanistic analysis performed in such humanized wound healing model. The deregulation of genes implicated in functions such as angiogenesis, apoptosis, and inflammatory signaling processes were evidenced, confirming published data in diabetic patients that in fact might also underlie some of the histological features previously reported in the delayed skin-humanized healing model. Altogether, these molecular findings support the utility of such preclinical model as a valuable tool to gain insight into the molecular basis of the delayed diabetic healing with potential impact in the translational medicine field.

}, keywords = {Animals, Diabetes Mellitus, Experimental, Gene Expression Profiling, Gene Expression Regulation, Gene ontology, Humans, Metabolic Networks and Pathways, Mice, Mice, Nude, Microarray Analysis, Molecular Sequence Annotation, Principal Component Analysis, Signal Transduction, Skin, Skin Transplantation, Skin Ulcer, Streptozocin, Tissue Engineering, Transcriptome, Transplantation, Heterologous, Wound Healing}, issn = {2073-4425}, doi = {10.3390/genes12010047}, author = {Le{\'o}n, Carlos and Garcia-Garcia, Francisco and Llames, Sara and Garc{\'\i}a-P{\'e}rez, Eva and Carretero, Marta and Arriba, Mar{\'\i}a Del Carmen and Dopazo, Joaquin and Del Rio, Marcela and Escamez, Maria Jos{\'e} and Mart{\'\i}nez-Santamar{\'\i}a, Luc{\'\i}a} } @article {439, title = {Integrated gene set analysis for microRNA studies.}, journal = {Bioinformatics}, volume = {32}, year = {2016}, month = {2016 Sep 15}, pages = {2809-16}, abstract = {

MOTIVATION: Functional interpretation of miRNA expression data is currently done in a three step procedure: select differentially expressed miRNAs, find their target genes, and carry out gene set overrepresentation analysis Nevertheless, major limitations of this approach have already been described at the gene level, while some newer arise in the miRNA scenario.Here, we propose an enhanced methodology that builds on the well-established gene set analysis paradigm. Evidence for differential expression at the miRNA level is transferred to a gene differential inhibition score which is easily interpretable in terms of gene sets or pathways. Such transferred indexes account for the additive effect of several miRNAs targeting the same gene, and also incorporate cancellation effects between cases and controls. Together, these two desirable characteristics allow for more accurate modeling of regulatory processes.

RESULTS: We analyze high-throughput sequencing data from 20 different cancer types and provide exhaustive reports of gene and Gene Ontology-term deregulation by miRNA action.

AVAILABILITY AND IMPLEMENTATION: The proposed methodology was implemented in the Bioconductor library mdgsa http://bioconductor.org/packages/mdgsa For the purpose of reproducibility all of the scripts are available at https://github.com/dmontaner-papers/gsa4mirna

CONTACT: : david.montaner@gmail.com

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

}, keywords = {Computational Biology, Gene Expression Profiling, Gene ontology, Gene Regulatory Networks, High-Throughput Nucleotide Sequencing, Humans, MicroRNAs, Neoplasms, Reproducibility of Results}, issn = {1367-4811}, doi = {10.1093/bioinformatics/btw334}, author = {Garcia-Garcia, Francisco and Panadero, Joaquin and Dopazo, Joaquin and Montaner, David} } @article {446, title = {Integrating transcriptomic and metabolomic analysis to understand natural leaf senescence in sunflower.}, journal = {Plant Biotechnol J}, volume = {14}, year = {2016}, month = {2016 Feb}, pages = {719-34}, abstract = {

Leaf senescence is a complex process, which has dramatic consequences on crop yield. In sunflower, gap between potential and actual yields reveals the economic impact of senescence. Indeed, sunflower plants are incapable of maintaining their green leaf area over sustained periods. This study characterizes the leaf senescence process in sunflower through a systems biology approach integrating transcriptomic and metabolomic analyses: plants being grown under both glasshouse and field conditions. Our results revealed a correspondence between profile changes detected at the molecular, biochemical and physiological level throughout the progression of leaf senescence measured at different plant developmental stages. Early metabolic changes were detected prior to anthesis and before the onset of the first senescence symptoms, with more pronounced changes observed when physiological and molecular variables were assessed under field conditions. During leaf development, photosynthetic activity and cell growth processes decreased, whereas sucrose, fatty acid, nucleotide and amino acid metabolisms increased. Pathways related to nutrient recycling processes were also up-regulated. Members of the NAC, AP2-EREBP, HB, bZIP and MYB transcription factor families showed high expression levels, and their expression level was highly correlated, suggesting their involvement in sunflower senescence. The results of this study thus contribute to the elucidation of the molecular mechanisms involved in the onset and progression of leaf senescence in sunflower leaves as well as to the identification of candidate genes involved in this process.

}, keywords = {Gas Chromatography-Mass Spectrometry, Gene Expression Profiling, Gene Expression Regulation, Plant, Gene ontology, Genes, Plant, Helianthus, Ions, metabolomics, Oligonucleotide Array Sequence Analysis, Plant Leaves, Principal Component Analysis, RNA, Messenger, Transcription Factors}, issn = {1467-7652}, doi = {10.1111/pbi.12422}, author = {Moschen, Sebasti{\'a}n and Bengoa Luoni, Sof{\'\i}a and Di Rienzo, Julio A and Caro, Mar{\'\i}a Del Pilar and Tohge, Takayuki and Watanabe, Mutsumi and Hollmann, Julien and Gonzalez, Sergio and Rivarola, M{\'a}ximo and Garcia-Garcia, Francisco and Dopazo, Joaquin and Hopp, Horacio Esteban and Hoefgen, Rainer and Fernie, Alisdair R and Paniego, Norma and Fernandez, Paula and Heinz, Ruth A} } @article {458, title = {Deregulation of key signaling pathways involved in oocyte maturation in FMR1 premutation carriers with Fragile X-associated primary ovarian insufficiency.}, journal = {Gene}, volume = {571}, year = {2015}, month = {2015 Oct 15}, pages = {52-7}, abstract = {

FMR1 premutation female carriers are at risk for Fragile X-associated primary ovarian insufficiency (FXPOI). Insights from knock-in mouse model have recently demonstrated that FXPOI is due to an increased rate of follicle depletion or an impaired development of the growing follicles. Molecular mechanisms responsible for this reduced viability are still unknown. In an attempt to provide new data on the mechanisms that lead to FXPOI, we report the first investigation involving transcription profiling of total blood from FMR1 premutation female carriers with and without FXPOI. A total of 16 unrelated female individuals (6 FMR1 premutated females with FXPOI; 6 FMR1 premutated females without FXPOI; and 4 no-FXPOI females) were studied by whole human genome oligonucleotide microarray (Agilent Technologies). Fold change analysis did not show any genes with significant differential gene expression. However, functional profiling by gene set analysis showed large number of statistically significant deregulated GO annotations as well as numerous KEGG pathways in FXPOI females. These results suggest that the impairment of fertility in these females might be due to a generalized deregulation of key signaling pathways involved in oocyte maturation. In particular, the vasoendotelial growth factor signaling, the inositol phosphate metabolism, the cell cycle, and the MAPK signaling pathways were found to be down-regulated in FXPOI females. Furthermore, a high statistical enrichment of biological processes involved in cell death and survival were found deregulated among FXPOI females. Our results provide new strategic approaches to further investigate the molecular mechanisms and potential therapeutic targets for FXPOI not focused in a single gene but rather in the set of genes involved in these pathways.

}, keywords = {Adult, Aged, Female, Fragile X Mental Retardation Protein, Fragile X Syndrome, Gene Expression Profiling, Gene Expression Regulation, Developmental, Gene ontology, Genome-Wide Association Study, Heterozygote, Humans, Middle Aged, Models, Genetic, mutation, Oligonucleotide Array Sequence Analysis, Oocytes, Primary Ovarian Insufficiency, Signal Transduction}, issn = {1879-0038}, doi = {10.1016/j.gene.2015.06.039}, author = {Alvarez-Mora, M I and Rodriguez-Revenga, L and Madrigal, I and Garc{\'\i}a-Garc{\'\i}a, F and Duran, M and Dopazo, J and Estivill, X and Mil{\`a}, M} } @article {483, title = {Sequencing and functional analysis of the genome of a nematode egg-parasitic fungus, Pochonia chlamydosporia.}, journal = {Fungal Genet Biol}, volume = {65}, year = {2014}, month = {2014 Apr}, pages = {69-80}, abstract = {

Pochonia chlamydosporia is a worldwide-distributed soil fungus with a great capacity to infect and destroy the eggs and kill females of plant-parasitic nematodes. Additionally, it has the ability to colonize endophytically roots of economically-important crop plants, thereby promoting their growth and eliciting plant defenses. This multitrophic behavior makes P. chlamydosporia a potentially useful tool for sustainable agriculture approaches. We sequenced and assembled \~{}41 Mb of P. chlamydosporia genomic DNA and predicted 12,122 gene models, of which many were homologous to genes of fungal pathogens of invertebrates and fungal plant pathogens. Predicted genes (65\%) were functionally annotated according to Gene Ontology, and 16\% of them found to share homology with genes in the Pathogen Host Interactions (PHI) database. The genome of this fungus is highly enriched in genes encoding hydrolytic enzymes, such as proteases, glycoside hydrolases and carbohydrate esterases. We used RNA-Seq technology in order to identify the genes expressed during endophytic behavior of P. chlamydosporia when colonizing barley roots. Functional annotation of these genes showed that hydrolytic enzymes and transporters are expressed during endophytism. This structural and functional analysis of the P. chlamydosporia genome provides a starting point for understanding the molecular mechanisms involved in the multitrophic lifestyle of this fungus. The genomic information provided here should also prove useful for enhancing the capabilities of this fungus as a biocontrol agent of plant-parasitic nematodes and as a plant growth-promoting organism.

}, keywords = {Animals, Ascomycota, Female, Gene Expression Regulation, Fungal, Gene ontology, Genome, Fungal, Hordeum, Host-Pathogen Interactions, Nematoda, Ovum, Phylogeny, Plant Roots, Sequence Analysis, DNA, Signal Transduction, Transcriptome}, issn = {1096-0937}, doi = {10.1016/j.fgb.2014.02.002}, author = {Larriba, Eduardo and Jaime, Mar{\'\i}a D L A and Carbonell-Caballero, Jos{\'e} and Conesa, Ana and Dopazo, Joaquin and Nislow, Corey and Mart{\'\i}n-Nieto, Jos{\'e} and Lopez-Llorca, Luis Vicente} }