@article {406, title = {The first complete genomic structure of Butyrivibrio fibrisolvens and its chromid.}, journal = {Microb Genom}, volume = {4}, year = {2018}, month = {2018 10}, abstract = {

Butyrivibrio fibrisolvens forms part of the gastrointestinal microbiome of ruminants and other mammals, including humans. Indeed, it is one of the most common bacteria found in the rumen and plays an important role in ruminal fermentation of polysaccharides, yet, to date, there is no closed reference genome published for this species in any ruminant animal. We successfully assembled the nearly complete genome sequence of B. fibrisolvens strain INBov1 isolated from cow rumen using Illumina paired-end reads, 454 Roche single-end and mate pair sequencing technology. Additionally, we constructed an optical restriction map of this strain to aid in scaffold ordering and positioning, and completed the first genomic structure of this species. Moreover, we identified and assembled the first chromid of this species (pINBov266). The INBov1 genome encodes a large set of genes involved in the cellulolytic process but lacks key genes. This seems to indicate that B. fibrisolvens plays an important role in ruminal cellulolytic processes, but does not have autonomous cellulolytic capacity. When searching for genes involved in the biohydrogenation of unsaturated fatty acids, no linoleate isomerase gene was found in this strain. INBov1 does encode oleate hydratase genes known to participate in the hydrogenation of oleic acids. Furthermore, INBov1 contains an enolase gene, which has been recently determined to participate in the synthesis of conjugated linoleic acids. This work confirms the presence of a novel chromid in B. fibrisolvens and provides a new potential reference genome sequence for this species, providing new insight into its role in biohydrogenation and carbohydrate degradation.

}, keywords = {Animals, Butyrivibrio fibrisolvens, Cattle, Genome, Bacterial, Genomics, Humans, Milk, Rumen, Sequence Analysis, DNA}, issn = {2057-5858}, doi = {10.1099/mgen.0.000216}, author = {Rodr{\'\i}guez Hern{\'a}ez, Javier and Cer{\'o}n Cucchi, Maria Esperanza and Cravero, Silvio and Martinez, Maria Carolina and Gonzalez, Sergio and Puebla, Andrea and Dopazo, Joaquin and Farber, Marisa and Paniego, Norma and Rivarola, M{\'a}ximo} } @article {461, title = {Family-based genome-wide association study in Patagonia confirms the association of the DMD locus and cleft lip and palate.}, journal = {Eur J Oral Sci}, volume = {123}, year = {2015}, month = {2015 Oct}, pages = {381-384}, abstract = {

The etiology of cleft lip with or without cleft palate (CL{\textpm}P) is complex and heterogeneous, and multiple genetic and environmental factors are involved. Some candidate genes reported to be associated with oral clefts are located on the X chromosome. At least three genes causing X-linked syndromes [midline 1 (MID1), oral-facial-digital syndrome 1 (OFD1), and dystrophin (DMD)] were previously found to be associated with isolated CL{\textpm}P. We attempted to confirm the role of X-linked genes in the etiology of isolated CL{\textpm}P in a South American population through a family-based genome-wide scan. We studied 27 affected children and their mothers, from 26 families, in a Patagonian population with a high prevalence of CL{\textpm}P. We conducted an exploratory analysis of the X chromosome to identify candidate regions associated with CL{\textpm}P. Four genomic segments were identified, two of which showed a statistically significant association with CL{\textpm}P. One is an 11-kb region of Xp21.1 containing the DMD gene, and the other is an intergenic region (8.7~kb; Xp11.4). Our results are consistent with recent data on the involvement of the DMD gene in the etiology of CL{\textpm}P. The MID1 and OFD1 genes were not included in the four potential CL{\textpm}P-associated X-chromosome genomic segments.

}, issn = {1600-0722}, doi = {10.1111/eos.12212}, author = {Fonseca, Renata F and de Carvalho, Fl{\'a}via M and Poletta, Fernando A and Montaner, David and Dopazo, Joaquin and Mereb, Juan C and Moreira, Miguel A M and Seuanez, Hector N and Vieira, Alexandre R and Castilla, Eduardo E and Orioli, I{\^e}da M} } @article {472, title = {Fast inexact mapping using advanced tree exploration on backward search methods.}, journal = {BMC Bioinformatics}, volume = {16}, year = {2015}, month = {2015 Jan 28}, pages = {18}, abstract = {

BACKGROUND: Short sequence mapping methods for Next Generation Sequencing consist on a combination of seeding techniques followed by local alignment based on dynamic programming approaches. Most seeding algorithms are based on backward search alignment, using the Burrows Wheeler Transform, the Ferragina and Manzini Index or Suffix Arrays. All these backward search algorithms have excellent performance, but their computational cost highly increases when allowing errors. In this paper, we discuss an inexact mapping algorithm based on pruning strategies for search tree exploration over genomic data.

RESULTS: The proposed algorithm achieves a 13x speed-up over similar algorithms when allowing 6 base errors, including insertions, deletions and mismatches. This algorithm can deal with 400 bps reads with up to 9 errors in a high quality Illumina dataset. In this example, the algorithm works as a preprocessor that reduces by 55\% the number of reads to be aligned. Depending on the aligner the overall execution time is reduced between 20-40\%.

CONCLUSIONS: Although not intended as a complete sequence mapping tool, the proposed algorithm could be used as a preprocessing step to modern sequence mappers. This step significantly reduces the number reads to be aligned, accelerating overall alignment time. Furthermore, this algorithm could be used for accelerating the seeding step of already available sequence mappers. In addition, an out-of-core index has been implemented for working with large genomes on systems without expensive memory configurations.

}, keywords = {Algorithms, Genome, Human, Genomics, High-Throughput Nucleotide Sequencing, Humans, Sequence Alignment, Sequence Analysis, DNA, Software}, issn = {1471-2105}, doi = {10.1186/s12859-014-0438-3}, author = {Salavert, Jos{\'e} and Tom{\'a}s, Andr{\'e}s and T{\'a}rraga, Joaqu{\'\i}n and Medina, Ignacio and Dopazo, Joaquin and Blanquer, Ignacio} } @article {515, title = {Four new loci associations discovered by pathway-based and network analyses of the genome-wide variability profile of Hirschsprung{\textquoteright}s disease.}, journal = {Orphanet J Rare Dis}, volume = {7}, year = {2012}, month = {2012 Dec 28}, pages = {103}, abstract = {

Finding gene associations in rare diseases is frequently hampered by the reduced numbers of patients accessible. Conventional gene-based association tests rely on the availability of large cohorts, which constitutes a serious limitation for its application in this scenario. To overcome this problem we have used here a combined strategy in which a pathway-based analysis (PBA) has been initially conducted to prioritize candidate genes in a Spanish cohort of 53 trios of short-segment Hirschsprung{\textquoteright}s disease. Candidate genes have been further validated in an independent population of 106 trios. The study revealed a strong association of 11 gene ontology (GO) modules related to signal transduction and its regulation, enteric nervous system (ENS) formation and other HSCR-related processes. Among the preselected candidates, a total of 4 loci, RASGEF1A, IQGAP2, DLC1 and CHRNA7, related to signal transduction and migration processes, were found to be significantly associated to HSCR. Network analysis also confirms their involvement in the network of already known disease genes. This approach, based on the study of functionally-related gene sets, requires of lower sample sizes and opens new opportunities for the study of rare diseases.

}, keywords = {Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Hirschsprung Disease, Humans, Male}, issn = {1750-1172}, doi = {10.1186/1750-1172-7-103}, author = {Fern{\'a}ndez, Raquel Ma and Bleda, Marta and N{\'u}{\~n}ez-Torres, Roc{\'\i}o and Medina, Ignacio and Luz{\'o}n-Toro, Berta and Garc{\'\i}a-Alonso, Luz and Torroglosa, Ana and Marb{\`a}, Martina and Enguix-Riego, Ma Valle and Montaner, David and Anti{\v n}olo, Guillermo and Dopazo, Joaquin and Borrego, Salud} } @article {879, title = {Fortunella margarita Transcriptional Reprogramming Triggered by Xanthomonas citri subsp. citri.}, journal = {BMC plant biology}, volume = {11}, year = {2011}, month = {2011}, pages = {159}, abstract = {ABSTRACT:}, issn = {1471-2229}, author = {Khalaf, Abeer A and Gmitter, Frederick G and Ana Conesa and Dopazo, Joaquin and Moore, Gloria A} } @article {19897487, title = {FM19G11, a new hypoxia-inducible factor (HIF) modulator, affects stem cell differentiation status.}, journal = {The Journal of biological chemistry}, volume = {285}, year = {2010}, month = {2010 Jan 8}, pages = {1333-42}, abstract = {

The biology of the alpha subunits of hypoxia-inducible factors (HIFalpha) has expanded from their role in angiogenesis to their current position in the self-renewal and differentiation of stem cells. The results reported in this article show the discovery of FM19G11, a novel chemical entity that inhibits HIFalpha proteins that repress target genes of the two alpha subunits, in various tumor cell lines as well as in adult and embryonic stem cell models from rodents and humans, respectively. FM19G11 inhibits at nanomolar range the transcriptional and protein expression of Oct4, Sox2, Nanog, and Tgf-alpha undifferentiating factors, in adult rat and human embryonic stem cells, FM19G11 activity occurs in ependymal progenitor stem cells from rats (epSPC), a cell model reported for spinal cord regeneration, which allows the progression of oligodendrocyte cell differentiation in a hypoxic environment, has created interest in its characterization for pharmacological research. Experiments using small interfering RNA showed a significant depletion in Sox2 protein only in the case of HIF2alpha silencing, but not in HIF1alpha-mediated ablation. Moreover, chromatin immunoprecipitation data, together with the significant presence of functional hypoxia response element consensus sequences in the promoter region of Sox2, strongly validated that this factor behaves as a target gene of HIF2alpha in epSPCs. FM19G11 causes a reduction of overall histone acetylation with significant repression of p300, a histone acetyltransferase required as a co-factor for HIF-transcription activation. Arrays carried out in the presence and absence of the inhibitor showed the predominant involvement of epigenetic-associated events mediated by the drug.

}, author = {Moreno-Manzano, Victoria and Rodr{\'\i}guez-Jim{\'e}nez, Francisco J and Ace{\~n}a-Bonilla, Jose L and Fustero-Lard{\'\i}es, Santos and Erceg, Slaven and Dopazo, Joaquin and Montaner, David and Stojkovic, Miodrag and S{\'a}nchez-Puelles, Jose M} } @article {552, title = {Functional genomics and networks: new approaches in the extraction of complex gene modules.}, journal = {Expert Rev Proteomics}, volume = {7}, year = {2010}, month = {2010 Feb}, pages = {55-63}, abstract = {

The engine that makes the cell work is made of an intricate network of molecular interactions. Nowadays, the elements and relationships of this complex network can be studied with several types of high-throughput techniques. The dream of having a global picture of the cell from different perspectives that can jointly explain cell behavior is, at least technically, feasible. However, this task can only be accomplished by filling the gap between data and information. The availability of methods capable of accurately managing, integrating and analyzing the results from these experiments is crucial for this purpose. Here, we review the new challenges raised by the availability of different genomic data, as well as the new proposals presented to cope with the increasing data complexity. Special emphasis is given to approaches that explore the transcriptome trying to describe the modules of genes that account for the traits studied.

}, keywords = {Gene Expression Regulation, Gene Regulatory Networks, Genomics, Protein Binding, Proteins, Systems biology}, issn = {1744-8387}, doi = {10.1586/epr.09.103}, author = {Minguez, Pablo and Dopazo, Joaquin} } @article {553, title = {Functional genomics of 5- to 8-cell stage human embryos by blastomere single-cell cDNA analysis.}, journal = {PLoS One}, volume = {5}, year = {2010}, month = {2010 Oct 26}, pages = {e13615}, abstract = {

Blastomere fate and embryonic genome activation (EGA) during human embryonic development are unsolved areas of high scientific and clinical interest. Forty-nine blastomeres from 5- to 8-cell human embryos have been investigated following an efficient single-cell cDNA amplification protocol to provide a template for high-density microarray analysis. The previously described markers, characteristic of Inner Cell Mass (ICM) (n = 120), stemness (n = 190) and Trophectoderm (TE) (n = 45), were analyzed, and a housekeeping pattern of 46 genes was established. All the human blastomeres from the 5- to 8-cell stage embryo displayed a common gene expression pattern corresponding to ICM markers (e.g., DDX3, FOXD3, LEFTY1, MYC, NANOG, POU5F1), stemness (e.g., POU5F1, DNMT3B, GABRB3, SOX2, ZFP42, TERT), and TE markers (e.g., GATA6, EOMES, CDX2, LHCGR). The EGA profile was also investigated between the 5-6- and 8-cell stage embryos, and compared to the blastocyst stage. Known genes (n = 92) such as depleted maternal transcripts (e.g., CCNA1, CCNB1, DPPA2) and embryo-specific activation (e.g., POU5F1, CDH1, DPPA4), as well as novel genes, were confirmed. In summary, the global single-cell cDNA amplification microarray analysis of the 5- to 8-cell stage human embryos reveals that blastomere fate is not committed to ICM or TE. Finally, new EGA features in human embryogenesis are presented.

}, keywords = {Blastomeres, DNA, Complementary, Gene Expression Profiling, Genomics, Humans, Oligonucleotide Array Sequence Analysis}, issn = {1932-6203}, doi = {10.1371/journal.pone.0013615}, author = {Galan, Amparo and Montaner, David and P{\'o}o, M Eugenia and Valbuena, Diana and Ruiz, Veronica and Aguilar, Crist{\'o}bal and Dopazo, Joaquin and Simon, Carlos} } @article {579, title = {Formulating and testing hypotheses in functional genomics.}, journal = {Artif Intell Med}, volume = {45}, year = {2009}, month = {2009 Feb-Mar}, pages = {97-107}, abstract = {

OBJECTIVE: The ultimate goal of any genome-scale experiment is to provide a functional interpretation of the results, relating the available genomic information to the hypotheses that originated the experiment.

METHODS AND RESULTS: Initially, this interpretation has been made on a pre-selection of relevant genes, based on the experimental values, followed by the study of the enrichment in some functional properties. Nevertheless, functional enrichment methods, demonstrated to have a flaw: the first step of gene selection was too stringent given that the cooperation among genes was ignored. The assumption that modules of genes related by relevant biological properties (functionality, co-regulation, chromosomal location, etc.) are the real actors of the cell biology lead to the development of new procedures, inspired in systems biology criteria, generically known as gene-set methods. These methods have been successfully used to analyze transcriptomic and large-scale genotyping experiments as well as to test other different genome-scale hypothesis in other fields such as phylogenomics.

}, keywords = {Biological Evolution, Computational Biology, Genomics, Genotype, Models, Theoretical}, issn = {1873-2860}, doi = {10.1016/j.artmed.2008.08.003}, author = {Dopazo, Joaquin} } @article {580, title = {Functional assessment of time course microarray data.}, journal = {BMC Bioinformatics}, volume = {10 Suppl 6}, year = {2009}, month = {2009 Jun 16}, pages = {S9}, abstract = {

MOTIVATION: Time-course microarray experiments study the progress of gene expression along time across one or several experimental conditions. Most developed analysis methods focus on the clustering or the differential expression analysis of genes and do not integrate functional information. The assessment of the functional aspects of time-course transcriptomics data requires the use of approaches that exploit the activation dynamics of the functional categories to where genes are annotated.

METHODS: We present three novel methodologies for the functional assessment of time-course microarray data. i) maSigFun derives from the maSigPro method, a regression-based strategy to model time-dependent expression patterns and identify genes with differences across series. maSigFun fits a regression model for groups of genes labeled by a functional class and selects those categories which have a significant model. ii) PCA-maSigFun fits a PCA model of each functional class-defined expression matrix to extract orthogonal patterns of expression change, which are then assessed for their fit to a time-dependent regression model. iii) ASCA-functional uses the ASCA model to rank genes according to their correlation to principal time expression patterns and assess functional enrichment on a GSA fashion. We used simulated and experimental datasets to study these novel approaches. Results were compared to alternative methodologies.

RESULTS: Synthetic and experimental data showed that the different methods are able to capture different aspects of the relationship between genes, functions and co-expression that are biologically meaningful. The methods should not be considered as competitive but they provide different insights into the molecular and functional dynamic events taking place within the biological system under study.

}, keywords = {Computer Simulation, Gene Expression Profiling, Oligonucleotide Array Sequence Analysis, Time Factors}, issn = {1471-2105}, doi = {10.1186/1471-2105-10-S6-S9}, author = {Nueda, Maria Jos{\'e} and Sebasti{\'a}n, Patricia and Tarazona, Sonia and Garcia-Garcia, Francisco and Dopazo, Joaquin and Ferrer, Alberto and Conesa, Ana} } @article {581, title = {Functional signatures identified in B-cell non-Hodgkin lymphoma profiles.}, journal = {Leuk Lymphoma}, volume = {50}, year = {2009}, month = {2009 Oct}, pages = {1699-708}, abstract = {

Gene-expression profiling in B-cell lymphomas has provided crucial data on specific lymphoma types, which can contribute to the identification of essential lymphoma survival genes and pathways. In this study, the gene-expression profiling data of all major B-cell lymphoma types were analyzed by unsupervised clustering. The transcriptome classification so obtained, was explored using gene set enrichment analysis generating a heatmap for B-cell lymphoma that identifies common lymphoma survival mechanisms and potential therapeutic targets, recognizing sets of coregulated genes and functional pathways expressed in different lymphoma types. Some of the most relevant signatures (stroma, cell cycle, B-cell receptor (BCR)) are shared by multiple lymphoma types or subclasses. A specific attention was paid to the analysis of BCR and coregulated pathways, defining molecular heterogeneity within multiple B-cell lymphoma types.

}, keywords = {Adult, Cluster Analysis, Gene Expression Profiling, Gene Expression Regulation, Leukemic, Genetic Heterogeneity, Humans, Lymphoma, B-Cell, Neoplasm Proteins, Oligonucleotide Array Sequence Analysis, RNA, Messenger, RNA, Neoplasm, Transcription, Genetic}, issn = {1029-2403}, doi = {10.1080/10428190903189035}, author = {Aggarwal, Mohit and S{\'a}nchez-Beato, Margarita and G{\'o}mez-L{\'o}pez, Gonzalo and Al-Shahrour, F{\'a}tima and Mart{\'\i}nez, Nerea and Rodr{\'\i}guez, Antonia and Ruiz-Ballesteros, Elena and Camacho, Francisca I and P{\'e}rez-Rosado, Alberto and de la Cueva, Paloma and Artiga, Mar{\'\i}a J and Pisano, David G and Kimby, Eva and Dopazo, Joaquin and Villuendas, Raquel and Piris, Miguel A} } @article {605, title = {FatiGO +: a functional profiling tool for genomic data. Integration of functional annotation, regulatory motifs and interaction data with microarray experiments.}, journal = {Nucleic Acids Res}, volume = {35}, year = {2007}, month = {2007 Jul}, pages = {W91-6}, abstract = {

The ultimate goal of any genome-scale experiment is to provide a functional interpretation of the data, relating the available information with the hypotheses that originated the experiment. Thus, functional profiling methods have become essential in diverse scenarios such as microarray experiments, proteomics, etc. We present the FatiGO+, a web-based tool for the functional profiling of genome-scale experiments, specially oriented to the interpretation of microarray experiments. In addition to different functional annotations (gene ontology, KEGG pathways, Interpro motifs, Swissprot keywords and text-mining based bioentities related to diseases and chemical compounds) FatiGO+ includes, as a novelty, regulatory and structural information. The regulatory information used includes predictions of targets for distinct regulatory elements (obtained from the Transfac and CisRed databases). Additionally FatiGO+ uses predictions of target motifs of miRNA to infer which of these can be activated or deactivated in the sample of genes studied. Finally, properties of gene products related to their relative location and connections in the interactome have also been used. Also, enrichment of any of these functional terms can be directly analysed on chromosomal coordinates. FatiGO+ can be found at: http://www.fatigoplus.org and within the Babelomics environment http://www.babelomics.org.

}, keywords = {Amino Acid Motifs, Animals, Binding Sites, Computational Biology, Gene Expression Profiling, Genes, Genomics, Humans, Internet, Oligonucleotide Array Sequence Analysis, Programming Languages, Software, Systems Integration, Transcription Factors}, issn = {1362-4962}, doi = {10.1093/nar/gkm260}, author = {Al-Shahrour, F{\'a}tima and Minguez, Pablo and T{\'a}rraga, Joaqu{\'\i}n and Medina, Ignacio and Alloza, Eva and Montaner, David and Dopazo, Joaquin} } @article {606, title = {From genes to functional classes in the study of biological systems.}, journal = {BMC Bioinformatics}, volume = {8}, year = {2007}, month = {2007 Apr 03}, pages = {114}, abstract = {

BACKGROUND: With the popularization of high-throughput techniques, the need for procedures that help in the biological interpretation of results has increased enormously. Recently, new procedures inspired in systems biology criteria have started to be developed.

RESULTS: Here we present FatiScan, a web-based program which implements a threshold-independent test for the functional interpretation of large-scale experiments that does not depend on the pre-selection of genes based on the multiple application of independent tests to each gene. The test implemented aims to directly test the behaviour of blocks of functionally related genes, instead of focusing on single genes. In addition, the test does not depend on the type of the data used for obtaining significance values, and consequently different types of biologically informative terms (gene ontology, pathways, functional motifs, transcription factor binding sites or regulatory sites from CisRed) can be applied to different classes of genome-scale studies. We exemplify its application in microarray gene expression, evolution and interactomics.

CONCLUSION: Methods for gene set enrichment which, in addition, are independent from the original data and experimental design constitute a promising alternative for the functional profiling of genome-scale experiments. A web server that performs the test described and other similar ones can be found at: http://www.babelomics.org.

}, keywords = {Algorithms, Chromosome Mapping, Computer Simulation, Gene Expression Profiling, Models, Biological, Multigene Family, Signal Transduction, Software, Systems biology, User-Computer Interface}, issn = {1471-2105}, doi = {10.1186/1471-2105-8-114}, author = {Al-Shahrour, F{\'a}tima and Arbiza, Leonardo and Dopazo, Hern{\'a}n and Huerta-Cepas, Jaime and Minguez, Pablo and Montaner, David and Dopazo, Joaquin} } @article {607, title = {Functional profiling and gene expression analysis of chromosomal copy number alterations.}, journal = {Bioinformation}, volume = {1}, year = {2007}, month = {2007 Apr 10}, pages = {432-5}, abstract = {

Contrarily to the traditional view in which only one or a few key genes were supposed to be the causative factors of diseases, we discuss the importance of considering groups of functionally related genes in the study of pathologies characterised by chromosomal copy number alterations. Recent observations have reported the existence of regions in higher eukaryotic chromosomes (including humans) containing genes of related function that show a high degree of coregulation. Copy number alterations will consequently affect to clusters of functionally related genes, which will be the final causative agents of the diseased phenotype, in many cases. Therefore, we propose that the functional profiling of the regions affected by copy number alterations must be an important aspect to take into account in the understanding of this type of pathologies. To illustrate this, we present an integrated study of DNA copy number variations, gene expression along with the functional profiling of chromosomal regions in a case of multiple myeloma.

}, issn = {0973-2063}, doi = {10.6026/97320630001432}, author = {Conde, Lucia and Montaner, David and Burguet-Castell, Jordi and T{\'a}rraga, Joaqu{\'\i}n and Al-Shahrour, F{\'a}tima and Dopazo, Joaquin} } @article {592, title = {Functional profiling of microarray experiments using text-mining derived bioentities.}, journal = {Bioinformatics}, volume = {23}, year = {2007}, month = {2007 Nov 15}, pages = {3098-9}, abstract = {

MOTIVATION: The increasing use of microarray technologies brought about a parallel demand in methods for the functional interpretation of the results. Beyond the conventional functional annotations for genes, such as gene ontology, pathways, etc. other sources of information are still to be exploited. Text-mining methods allow extracting informative terms (bioentities) with different functional, chemical, clinical, etc. meanings, that can be associated to genes. We show how to use these associations within an appropriate statistical framework and how to apply them through easy-to-use, web-based environments to the functional interpretation of microarray experiments. Functional enrichment and gene set enrichment tests using bioentities are presented.

}, keywords = {Artificial Intelligence, Databases, Protein, Gene Expression Profiling, Information Storage and Retrieval, Natural Language Processing, Proteins, Research Design, Systems Integration}, issn = {1367-4811}, doi = {10.1093/bioinformatics/btm445}, author = {Minguez, Pablo and Al-Shahrour, F{\'a}tima and Montaner, David and Dopazo, Joaquin} }