16 results on '"de las Rivas, J."'
Search Results
2. Encompassing new use cases - level 3.0 of the HUPO-PSI format for molecular interactions
- Author
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Sivade (Dumousseau), M., Alonso-López, D., Ammari, M., Bradley, G., Campbell, N. H., Ceol, A., Cesareni, G., Combe, C., De Las Rivas, J., del-Toro, N., Heimbach, J., Hermjakob, H., Jurisica, I., Koch, M., Licata, L., Lovering, R. C., Lynn, D. J., Meldal, B. H. M., Micklem, G., Panni, S., Porras, P., Ricard-Blum, S., Roechert, B., Salwinski, L., Shrivastava, A., Sullivan, J., Thierry-Mieg, N., Yehudi, Y., Van Roey, K., and Orchard, S.
- Published
- 2018
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3. Analysis of asymptomatic Drosophila models for ALS and SMA reveals convergent impact on functional protein complexes linked to neuro-muscular degeneration.
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Garcia-Vaquero ML, Heim M, Flix B, Pereira M, Palin L, Marques TM, Pinto FR, de Las Rivas J, Voigt A, Besse F, and Gama-Carvalho M
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- Adult, Humans, Animals, Drosophila genetics, Motor Neurons, RNA, DNA-Binding Proteins, Amyotrophic Lateral Sclerosis genetics, Muscular Atrophy, Spinal, Drosophila Proteins genetics
- Abstract
Background: Spinal Muscular Atrophy (SMA) and Amyotrophic Lateral Sclerosis (ALS) share phenotypic and molecular commonalities, including the fact that they can be caused by mutations in ubiquitous proteins involved in RNA metabolism, namely SMN, TDP-43 and FUS. Although this suggests the existence of common disease mechanisms, there is currently no model to explain the resulting motor neuron dysfunction. In this work we generated a parallel set of Drosophila models for adult-onset RNAi and tagged neuronal expression of the fly orthologues of the three human proteins, named Smn, TBPH and Caz, respectively. We profiled nuclear and cytoplasmic bound mRNAs using a RIP-seq approach and characterized the transcriptome of the RNAi models by RNA-seq. To unravel the mechanisms underlying the common functional impact of these proteins on neuronal cells, we devised a computational approach based on the construction of a tissue-specific library of protein functional modules, selected by an overall impact score measuring the estimated extent of perturbation caused by each gene knockdown., Results: Transcriptome analysis revealed that the three proteins do not bind to the same RNA molecules and that only a limited set of functionally unrelated transcripts is commonly affected by their knock-down. However, through our integrative approach we were able to identify a concerted effect on protein functional modules, albeit acting through distinct targets. Most strikingly, functional annotation revealed that these modules are involved in critical cellular pathways for motor neurons, including neuromuscular junction function. Furthermore, selected modules were found to be significantly enriched in orthologues of human neuronal disease genes., Conclusions: The results presented here show that SMA and ALS disease-associated genes linked to RNA metabolism functionally converge on neuronal protein complexes, providing a new hypothesis to explain the common motor neuron phenotype. The functional modules identified represent promising biomarkers and therapeutic targets, namely given their alteration in asymptomatic settings., (© 2023. BioMed Central Ltd., part of Springer Nature.)
- Published
- 2023
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4. METTL1 promotes tumorigenesis through tRNA-derived fragment biogenesis in prostate cancer.
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García-Vílchez R, Añazco-Guenkova AM, Dietmann S, López J, Morón-Calvente V, D'Ambrosi S, Nombela P, Zamacola K, Mendizabal I, García-Longarte S, Zabala-Letona A, Astobiza I, Fernández S, Paniagua A, Miguel-López B, Marchand V, Alonso-López D, Merkel A, García-Tuñón I, Ugalde-Olano A, Loizaga-Iriarte A, Lacasa-Viscasillas I, Unda M, Azkargorta M, Elortza F, Bárcena L, Gonzalez-Lopez M, Aransay AM, Di Domenico T, Sánchez-Martín MA, De Las Rivas J, Guil S, Motorin Y, Helm M, Pandolfi PP, Carracedo A, and Blanco S
- Subjects
- Male, Humans, Cell Transformation, Neoplastic, Transcription, Genetic, RNA Processing, Post-Transcriptional, Methyltransferases genetics, Carcinogenesis genetics, Prostatic Neoplasms genetics
- Abstract
Newly growing evidence highlights the essential role that epitranscriptomic marks play in the development of many cancers; however, little is known about the role and implications of altered epitranscriptome deposition in prostate cancer. Here, we show that the transfer RNA N
7 -methylguanosine (m7 G) transferase METTL1 is highly expressed in primary and advanced prostate tumours. Mechanistically, we find that METTL1 depletion causes the loss of m7 G tRNA methylation and promotes the biogenesis of a novel class of small non-coding RNAs derived from 5'tRNA fragments. 5'tRNA-derived small RNAs steer translation control to favour the synthesis of key regulators of tumour growth suppression, interferon pathway, and immune effectors. Knockdown of Mettl1 in prostate cancer preclinical models increases intratumoural infiltration of pro-inflammatory immune cells and enhances responses to immunotherapy. Collectively, our findings reveal a therapeutically actionable role of METTL1-directed m7 G tRNA methylation in cancer cell translation control and tumour biology., (© 2023. The Author(s).)- Published
- 2023
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5. Cancer-associated fibroblast-derived gene signatures determine prognosis in colon cancer patients.
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Herrera M, Berral-González A, López-Cade I, Galindo-Pumariño C, Bueno-Fortes S, Martín-Merino M, Carrato A, Ocaña A, De La Pinta C, López-Alfonso A, Peña C, García-Barberán V, and De Las Rivas J
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- Cancer-Associated Fibroblasts pathology, Colonic Neoplasms genetics, Colonic Neoplasms metabolism, Colonic Neoplasms pathology, Exosomes metabolism, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Humans, Neoplasm Staging, Prognosis, Biomarkers, Tumor, Cancer-Associated Fibroblasts metabolism, Colonic Neoplasms mortality, Tumor Microenvironment genetics
- Published
- 2021
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6. Survival marker genes of colorectal cancer derived from consistent transcriptomic profiling.
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Martinez-Romero J, Bueno-Fortes S, Martín-Merino M, Ramirez de Molina A, and De Las Rivas J
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- Humans, Prognosis, Survival Rate, Biomarkers, Tumor genetics, Colorectal Neoplasms genetics, Colorectal Neoplasms mortality, Gene Expression Profiling methods, Gene Expression Regulation, Neoplastic
- Abstract
Background: Identification of biomarkers associated with the prognosis of different cancer subtypes is critical to achieve better therapeutic assistance. In colorectal cancer (CRC) the discovery of stable and consistent survival markers remains a challenge due to the high heterogeneity of this class of tumors. In this work, we identified a new set of gene markers for CRC associated to prognosis and risk using a large unified cohort of patients with transcriptomic profiles and survival information., Results: We built an integrated dataset with 1273 human colorectal samples, which provides a homogeneous robust framework to analyse genome-wide expression and survival data. Using this dataset we identified two sets of genes that are candidate prognostic markers for CRC in stages III and IV, showing either up-regulation correlated with poor prognosis or up-regulation correlated with good prognosis. The top 10 up-regulated genes found as survival markers of poor prognosis (i.e. low survival) were: DCBLD2, PTPN14, LAMP5, TM4SF1, NPR3, LEMD1, LCA5, CSGALNACT2, SLC2A3 and GADD45B. The stability and robustness of the gene survival markers was assessed by cross-validation, and the best-ranked genes were also validated with two external independent cohorts: one of microarrays with 482 samples; another of RNA-seq with 269 samples. Up-regulation of the top genes was also proved in a comparison with normal colorectal tissue samples. Finally, the set of top 100 genes that showed overexpression correlated with low survival was used to build a CRC risk predictor applying a multivariate Cox proportional hazards regression analysis. This risk predictor yielded an optimal separation of the individual patients of the cohort according to their survival, with a p-value of 8.25e-14 and Hazard Ratio 2.14 (95% CI: 1.75-2.61)., Conclusions: The results presented in this work provide a solid rationale for the prognostic utility of a new set of genes in CRC, demonstrating their potential to predict colorectal tumor progression and evolution towards poor survival stages. Our study does not provide a fixed gene signature for prognosis and risk prediction, but instead proposes a robust set of genes ranked according to their predictive power that can be selected for additional tests with other CRC clinical cohorts.
- Published
- 2018
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7. Identification of expression patterns in the progression of disease stages by integration of transcriptomic data.
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Aibar S, Abaigar M, Campos-Laborie FJ, Sánchez-Santos JM, Hernandez-Rivas JM, and De Las Rivas J
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- Algorithms, Alzheimer Disease genetics, Alzheimer Disease metabolism, Alzheimer Disease pathology, Cluster Analysis, Colorectal Neoplasms genetics, Colorectal Neoplasms pathology, Databases, Genetic, Disease Progression, Humans, Myelodysplastic Syndromes genetics, Myelodysplastic Syndromes metabolism, Myelodysplastic Syndromes pathology, Neoplasm Staging, Sequence Analysis, RNA, Severity of Illness Index, Gene Expression Profiling methods, Transcriptome
- Abstract
Background: In the study of complex diseases using genome-wide expression data from clinical samples, a difficult case is the identification and mapping of the gene signatures associated to the stages that occur in the progression of a disease. The stages usually correspond to different subtypes or classes of the disease, and the difficulty to identify them often comes from patient heterogeneity and sample variability that can hide the biomedical relevant changes that characterize each stage, making standard differential analysis inadequate or inefficient., Results: We propose a methodology to study diseases or disease stages ordered in a sequential manner (e.g. from early stages with good prognosis to more acute or serious stages associated to poor prognosis). The methodology is applied to diseases that have been studied obtaining genome-wide expression profiling of cohorts of patients at different stages. The approach allows searching for consistent expression patterns along the progression of the disease through two major steps: (i) identifying genes with increasing or decreasing trends in the progression of the disease; (ii) clustering the increasing/decreasing gene expression patterns using an unsupervised approach to reveal whether there are consistent patterns and find genes altered at specific disease stages. The first step is carried out using Gamma rank correlation to identify genes whose expression correlates with a categorical variable that represents the stages of the disease. The second step is done using a Self Organizing Map (SOM) to cluster the genes according to their progressive profiles and identify specific patterns. Both steps are done after normalization of the genomic data to allow the integration of multiple independent datasets. In order to validate the results and evaluate their consistency and biological relevance, the methodology is applied to datasets of three different diseases: myelodysplastic syndrome, colorectal cancer and Alzheimer's disease. A software script written in R, named genediseasePatterns, is provided to allow the use and application of the methodology., Conclusion: The method presented allows the analysis of the progression of complex and heterogeneous diseases that can be divided in pathological stages. It identifies gene groups whose expression patterns change along the advance of the disease, and it can be applied to different types of genomic data studying cohorts of patients in different states.
- Published
- 2016
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8. Insights into the human mesenchymal stromal/stem cell identity through integrative transcriptomic profiling.
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Roson-Burgo B, Sanchez-Guijo F, Del Cañizo C, and De Las Rivas J
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- Adipose Tissue cytology, Biomarkers, Bone Marrow Cells cytology, Bone Marrow Cells metabolism, Cell Differentiation genetics, Cell Lineage genetics, Cluster Analysis, Computational Biology methods, Female, Gene Expression Profiling, Gene Expression Regulation, Developmental, Gene Regulatory Networks, Humans, Mesenchymal Stem Cells cytology, Organ Specificity genetics, Placenta cytology, Pregnancy, Mesenchymal Stem Cells metabolism, Transcriptome
- Abstract
Background: Mesenchymal Stromal/Stem Cells (MSCs), isolated under the criteria established by the ISCT, still have a poorly characterized phenotype that is difficult to distinguish from similar cell populations. Although the field of transcriptomics and functional genomics has quickly grown in the last decade, a deep comparative analysis of human MSCs expression profiles in a meaningful cellular context has not been yet performed. There is also a need to find a well-defined MSCs gene-signature because many recent biomedical studies show that key cellular interaction processes (i.e. inmuno-modulation, cellular cross-talk, cellular maintenance, differentiation, epithelial-mesenchymal transition) are dependent on the mesenchymal stem cells within the stromal niche., Results: In this work we define a core mesenchymal lineage signature of 489 genes based on a deep comparative analysis of multiple transcriptomic expression data series that comprise: (i) MSCs of different tissue origins; (ii) MSCs in different states of commitment; (iii) other related non-mesenchymal human cell types. The work integrates several public datasets, as well as de-novo produced microarray and RNA-Seq datasets. The results present tissue-specific signatures for adipose tissue, chorionic placenta, and bone marrow MSCs, as well as for dermal fibroblasts; providing a better definition of the relationship between fibroblasts and MSCs. Finally, novel CD marker patterns and cytokine-receptor profiles are unravelled, especially for BM-MSCs; with MCAM (CD146) revealed as a prevalent marker in this subtype of MSCs., Conclusions: The improved biomolecular characterization and the released genome-wide expression signatures of human MSCs provide a comprehensive new resource that can drive further functional studies and redesigned cell therapy applications.
- Published
- 2016
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9. Evolutionary hallmarks of the human proteome: chasing the age and coregulation of protein-coding genes.
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Lopes KP, Campos-Laborie FJ, Vialle RA, Ortega JM, and De Las Rivas J
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- Cluster Analysis, Computational Biology methods, Gene Expression Profiling, Gene Expression Regulation, Gene Regulatory Networks, Genomics methods, High-Throughput Nucleotide Sequencing, Humans, Molecular Sequence Annotation, Open Reading Frames, Organ Specificity genetics, Transcriptome, Evolution, Molecular, Proteome, Proteomics methods
- Abstract
Background: The development of large-scale technologies for quantitative transcriptomics has enabled comprehensive analysis of the gene expression profiles in complete genomes. RNA-Seq allows the measurement of gene expression levels in a manner far more precise and global than previous methods. Studies using this technology are altering our view about the extent and complexity of the eukaryotic transcriptomes. In this respect, multiple efforts have been done to determine and analyse the gene expression patterns of human cell types in different conditions, either in normal or pathological states. However, until recently, little has been reported about the evolutionary marks present in human protein-coding genes, particularly from the combined perspective of gene expression and protein evolution., Results: We present a combined analysis of human protein-coding gene expression profiling and time-scale ancestry mapping, that places the genes in taxonomy clades and reveals eight evolutionary major steps ("hallmarks"), that include clusters of functionally coherent proteins. The human expressed genes are analysed using a RNA-Seq dataset of 116 samples from 32 tissues. The evolutionary analysis of the human proteins is performed combining the information from: (i) a database of orthologous proteins (OMA), (ii) the taxonomy mapping of genes to lineage clades (from NCBI Taxonomy) and (iii) the evolution time-scale mapping provided by TimeTree (Timescale of Life). The human protein-coding genes are also placed in a relational context based in the construction of a robust gene coexpression network, that reveals tighter links between age-related protein-coding genes and finds functionally coherent gene modules., Conclusions: Understanding the relational landscape of the human protein-coding genes is essential for interpreting the functional elements and modules of our active genome. Moreover, decoding the evolutionary history of the human genes can provide very valuable information to reveal or uncover their origin and function.
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- 2016
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10. Path2enet: generation of human pathway-derived networks in an expression specific context.
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Droste C and De Las Rivas J
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- B-Lymphocytes immunology, B-Lymphocytes metabolism, Gene Expression Profiling methods, Gene Expression Regulation, Humans, Software, T-Lymphocytes immunology, T-Lymphocytes metabolism, Web Browser, Computational Biology methods, Gene Regulatory Networks, Signal Transduction
- Abstract
Background: Biological pathways are subsets of the complex biomolecular wiring that occur in living cells. They are usually rationalized and depicted in cartoon maps or charts to show them in a friendly visible way. Despite these efforts to present biological pathways, the current progress of bioinformatics indicates that translation of pathways in networks can be a very useful approach to achieve a computer-based view of the complex processes and interactions that occurr in a living system., Results: We have developed a bioinformatic tool called Path2enet that provides a translation of biological pathways in protein networks integrating several layers of information about the biomolecular nodes in a multiplex view. Path2enet is an R package that reads the relations and links between proteins stored in a comprehensive database of biological pathways, KEGG (Kyoto Encyclopedia of Genes and Genomes, http://www.genome.jp/kegg/ ), and integrates them with expression data from various resources and with data on protein-protein physical interactions. Path2enet tool uses the expression data to determine if a given protein in a network (i.e., a node) is active (ON) or inactive (OFF) in a specific cellular context or sample type. In this way, Path2enet reduces the complexity of the networks and reveals the proteins that are active (expressed) under specific conditions. As a proof of concept, this work presents a practical "case of use" generating the pathway-expression-networks corresponding to the NOTCH Signaling Pathway in human B- and T-lymphocytes. This case is produced by the analysis and integration in Path2enet of an experimental dataset of genome-wide expression microarrays produced with these cell types (i.e., B cells and T cells)., Conclusions: Path2enet is an open source and open access tool that allows the construction of pathway-expression-networks, reading and integrating the information from biological pathways, protein interactions and gene expression cell specific data. The development of this type of tools aims to provide a more integrative and global view of the links and associations that exist between the proteins working in specific cellular systems.
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- 2016
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11. Analyse multiple disease subtypes and build associated gene networks using genome-wide expression profiles.
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Aibar S, Fontanillo C, Droste C, Roson-Burgo B, Campos-Laborie FJ, Hernandez-Rivas JM, and De Las Rivas J
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- Base Sequence, Gene Expression Regulation, Neoplastic, Gene Regulatory Networks, Genetic Predisposition to Disease, Humans, Leukemia classification, Oligonucleotide Array Sequence Analysis, Sequence Analysis, RNA, Biomarkers, Tumor genetics, Computational Biology methods, Gene Expression Profiling methods, Genetic Markers genetics, Leukemia genetics
- Abstract
Background: Despite the large increase of transcriptomic studies that look for gene signatures on diseases, there is still a need for integrative approaches that obtain separation of multiple pathological states providing robust selection of gene markers for each disease subtype and information about the possible links or relations between those genes., Results: We present a network-oriented and data-driven bioinformatic approach that searches for association of genes and diseases based on the analysis of genome-wide expression data derived from microarrays or RNA-Seq studies. The approach aims to (i) identify gene sets associated to different pathological states analysed together; (ii) identify a minimum subset within these genes that unequivocally differentiates and classifies the compared disease subtypes; (iii) provide a measurement of the discriminant power of these genes and (iv) identify links between the genes that characterise each of the disease subtypes. This bioinformatic approach is implemented in an R package, named geNetClassifier, available as an open access tool in Bioconductor. To illustrate the performance of the tool, we applied it to two independent datasets: 250 samples from patients with four major leukemia subtypes analysed using expression arrays; another leukemia dataset analysed with RNA-Seq that includes a subtype also present in the previous set. The results show the selection of key deregulated genes recently reported in the literature and assigned to the leukemia subtypes studied. We also show, using these independent datasets, the selection of similar genes in a network built for the same disease subtype., Conclusions: The construction of gene networks related to specific disease subtypes that include parameters such as gene-to-gene association, gene disease specificity and gene discriminant power can be very useful to draw gene-disease maps and to unravel the molecular features that characterize specific pathological states. The application of the bioinformatic tool here presented shows a neat way to achieve such molecular characterization of the diseases using genome-wide expression data.
- Published
- 2015
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12. Transcriptomic portrait of human Mesenchymal Stromal/Stem Cells isolated from bone marrow and placenta.
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Roson-Burgo B, Sanchez-Guijo F, Del Cañizo C, and De Las Rivas J
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- Adult, Antigens, CD genetics, Biomarkers metabolism, Cell Culture Techniques, Cell Separation, DNA Methylation, Female, Gene Expression Profiling, Humans, Kruppel-Like Factor 4, Male, Middle Aged, Pregnancy, Transcription Factors metabolism, Bone Marrow Cells cytology, Mesenchymal Stem Cells cytology, Mesenchymal Stem Cells metabolism, Placenta cytology
- Abstract
Background: Human Mesenchymal Stromal/Stem Cells (MSCs) are adult multipotent cells that behave in a highly plastic manner, inhabiting the stroma of several tissues. The potential utility of MSCs is nowadays strongly investigated in the field of regenerative medicine and cell therapy, although many questions about their molecular identity remain uncertain., Results: MSC primary cultures from human bone marrow (BM) and placenta (PL) were derived and verified by their immunophenotype standard pattern and trilineage differentiation potential. Then, a broad characterization of the transcriptome of these MSCs was performed using RNA deep sequencing (RNA-Seq). Quantitative analysis of these data rendered an extensive expression footprint that includes 5,271 protein-coding genes. Flow cytometry assays of canonical MSC CD-markers were congruent with their expression levels detected by the RNA-Seq. Expression of other recently proposed MSC markers (CD146, Nestin and CD271) was tested in the placenta samples, finding only CD146 and Nestin. Functional analysis revealed enrichment in stem cell related genes and mesenchymal regulatory transcription factors (TFs). Analysis of TF binding sites (TFBSs) identified 11 meta-regulators, including factors KLF4 and MYC among them. Epigenetically, hypomethylated promoter patterns supported the active expression of the MSC TFs found. An interaction network of these TFs was built to show up their links and relations. Assessment of dissimilarities between cell origins (BM versus PL) disclosed two hundred differentially expressed genes enrolled in microenvironment processes related to the cellular niche, as regulation of bone formation and blood vessel morphogenesis for the case of BM-MSCs. By contrast genes overexpressed in PL-MSCs showed functional enrichment on mitosis, negative regulation of cell-death and embryonic morphogenesis that supported the higher growth rates observed in the cultures of these fetal cells and their closer links with development processes., Conclusions: The results present a transcriptomic portrait of the human MSCs isolated from bone marrow and placenta. The data are released as a cell-specific resource, providing a comprehensive expression footprint of the MSCs useful to better understand their cellular and molecular biology and for further investigations on the isolation and biomedical use of these multipotent cells.
- Published
- 2014
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13. A robust estimation of exon expression to identify alternative spliced genes applied to human tissues and cancer samples.
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Risueño A, Roson-Burgo B, Dolnik A, Hernandez-Rivas JM, Bullinger L, and De Las Rivas J
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- Algorithms, Databases, Genetic, Exons, Humans, Organ Specificity, Reproducibility of Results, Alternative Splicing, Gene Expression Profiling methods, Leukemia, Myeloid, Acute genetics, Oligonucleotide Array Sequence Analysis methods, Protein Isoforms genetics
- Abstract
Background: Accurate analysis of whole-gene expression and individual-exon expression is essential to characterize different transcript isoforms and identify alternative splicing events in human genes. One of the omic technologies widely used in many studies on human samples are the exon-specific expression microarray platforms., Results: Since there are not many validated comparative analyses to identify specific splicing events using data derived from these types of platforms, we have developed an algorithm (called ESLiM) to detect significant changes in exon use, and applied it to a reference dataset of 270 human genes that show alternative expression in different tissues. We compared the results with three other methodological approaches and provided the R source code to be applied elsewhere. The genes positively detected by these analyses also provide a verified subset of human genes that present tissue-regulated isoforms. Furthermore, we performed a validation analysis on human patient samples comparing two different subtypes of acute myeloid leukemia (AML) and we experimentally validated the splicing in several selected genes that showed exons with highly significant signal change., Conclusions: The comparative analyses with other methods using a fair set of human genes that show alternative splicing and the validation on clinical samples demonstrate that the proposed novel algorithm is a reliable tool for detecting differential splicing in exon-level expression data.
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- 2014
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14. Combined analysis of genome-wide expression and copy number profiles to identify key altered genomic regions in cancer.
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Fontanillo C, Aibar S, Sanchez-Santos JM, and De Las Rivas J
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- Humans, Algorithms, Gene Dosage genetics, Genome, Human genetics, Genomics methods, Glioblastoma genetics, Models, Genetic, Transcriptome
- Abstract
Background: Analysis of DNA copy number alterations and gene expression changes in human samples have been used to find potential target genes in complex diseases. Recent studies have combined these two types of data using different strategies, but focusing on finding gene-based relationships. However, it has been proposed that these data can be used to identify key genomic regions, which may enclose causal genes under the assumption that disease-associated gene expression changes are caused by genomic alterations.
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- 2012
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15. GATExplorer: genomic and transcriptomic explorer; mapping expression probes to gene loci, transcripts, exons and ncRNAs.
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Risueño A, Fontanillo C, Dinger ME, and De Las Rivas J
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- Animals, Chromosome Mapping, Databases, Genetic, Genetic Loci, Humans, Mice, Oligonucleotide Array Sequence Analysis, RNA, Untranslated chemistry, Rats, Exons genetics, Gene Expression Profiling, Genome, Genomics methods, Oligonucleotide Probes, RNA, Untranslated genetics, Software
- Abstract
Background: Genome-wide expression studies have developed exponentially in recent years as a result of extensive use of microarray technology. However, expression signals are typically calculated using the assignment of "probesets" to genes, without addressing the problem of "gene" definition or proper consideration of the location of the measuring probes in the context of the currently known genomes and transcriptomes. Moreover, as our knowledge of metazoan genomes improves, the number of both protein-coding and noncoding genes, as well as their associated isoforms, continues to increase. Consequently, there is a need for new databases that combine genomic and transcriptomic information and provide updated mapping of expression probes to current genomic annotations., Results: GATExplorer (Genomic and Transcriptomic Explorer) is a database and web platform that integrates a gene loci browser with nucleotide level mappings of oligo probes from expression microarrays. It allows interactive exploration of gene loci, transcripts and exons of human, mouse and rat genomes, and shows the specific location of all mappable Affymetrix microarray probes and their respective expression levels in a broad set of biological samples. The web site allows visualization of probes in their genomic context together with any associated protein-coding or noncoding transcripts. In the case of all-exon arrays, this provides a means by which the expression of the individual exons within a gene can be compared, thereby facilitating the identification and analysis of alternatively spliced exons. The application integrates data from four major source databases: Ensembl, RNAdb, Affymetrix and GeneAtlas; and it provides the users with a series of files and packages (R CDFs) to analyze particular query expression datasets. The maps cover both the widely used Affymetrix GeneChip microarrays based on 3' expression (e.g. human HG U133 series) and the all-exon expression microarrays (Gene 1.0 and Exon 1.0)., Conclusions: GATExplorer is an integrated database that combines genomic/transcriptomic visualization with nucleotide-level probe mapping. By considering expression at the nucleotide level rather than the gene level, it shows that the arrays detect expression signals from entities that most researchers do not contemplate or discriminate. This approach provides the means to undertake a higher resolution analysis of microarray data and potentially extract considerably more detailed and biologically accurate information from existing and future microarray experiments.
- Published
- 2010
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16. Linear array of conserved sequence motifs to discriminate protein subfamilies: study on pyridine nucleotide-disulfide reductases.
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Avila CL, Rapisarda VA, Farías RN, De Las Rivas J, and Chehín R
- Subjects
- Amino Acid Motifs, Amino Acid Sequence, Computer Simulation, Conserved Sequence, Discriminant Analysis, Disulfides chemistry, Linear Models, Models, Chemical, Molecular Sequence Data, Nucleotides chemistry, Oxidoreductases classification, Sequence Homology, Amino Acid, Oxidoreductases chemistry, Pyridines chemistry, Sequence Alignment methods, Sequence Analysis, Protein methods
- Abstract
Background: The pyridine nucleotide disulfide reductase (PNDR) is a large and heterogeneous protein family divided into two classes (I and II), which reflect the divergent evolution of its characteristic disulfide redox active site. However, not all the PNDR members fit into these categories and this suggests the need of further studies to achieve a more comprehensive classification of this complex family., Results: A workflow to improve the clusterization of protein families based on the array of linear conserved motifs is designed. The method is applied to the PNDR large family finding two main groups, which correspond to PNDR classes I and II. However, two other separate protein clusters, previously classified as class I in most databases, are outgrouped: the peroxide reductases (NAOX, NAPE) and the type II NADH dehydrogenases (NDH-2). In this way, two novel PNDR classes III and IV for NAOX/NAPE and NDH-2 respectively are proposed. By knowledge-driven biochemical and functional data analyses done on the new class IV, a linear array of motifs putatively related to Cu(II)-reductase activity is detected in a specific subset of NDH-2., Conclusion: The results presented are a novel contribution to the classification of the complex and large PNDR protein family, supporting its reclusterization into four classes. The linear array of motifs detected within the class IV PNDR subfamily could be useful as a signature for a particular subgroup of NDH-2.
- Published
- 2007
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