02676nas a2200541 4500008004100000022001400041245013100055210006900186260000900255300000900264490000600273520115300279653001201432100002001444700002001464700001601484700001701500700002501517700001601542700002001558700001801578700002101596700001801617700002001635700002001655700002101675700001401696700001501710700001801725700001901743700002601762700002701788700002701815700001601842700001301858700002101871700002601892700001801918700001601936700001801952700001501970700001501985700001302000700001502013700001302028700001602041856007702057 2014 eng d a2041-172300aAssessing technical performance in differential gene expression experiments with external spike-in RNA control ratio mixtures.0 aAssessing technical performance in differential gene expression  c2014 a51250 v53 aThere is a critical need for standard approaches to assess, report and compare the technical performance of genome-scale differential gene expression experiments. Here we assess technical performance with a proposed standard ’dashboard’ of metrics derived from analysis of external spike-in RNA control ratio mixtures. These control ratio mixtures with defined abundance ratios enable assessment of diagnostic performance of differentially expressed transcript lists, limit of detection of ratio (LODR) estimates and expression ratio variability and measurement bias. The performance metrics suite is applicable to analysis of a typical experiment, and here we also apply these metrics to evaluate technical performance among laboratories. An interlaboratory study using identical samples shared among 12 laboratories with three different measurement processes demonstrates generally consistent diagnostic power across 11 laboratories. Ratio measurement variability and bias are also comparable among laboratories for the same measurement process. We observe different biases for measurement processes using different mRNA-enrichment protocols.10aRNA-seq1 aMunro, Sarah, A1 aLund, Steven, P1 aPine, Scott1 aBinder, Hans1 aClevert, Djork-Arné1 aConesa, Ana1 aDopazo, Joaquin1 aFasold, Mario1 aHochreiter, Sepp1 aHong, Huixiao1 aJafari, Nadereh1 aKreil, David, P1 aLabaj, Paweł, P1 aLi, Sheng1 aLiao, Yang1 aLin, Simon, M1 aMeehan, Joseph1 aMason, Christopher, E1 aSantoyo-López, Javier1 aSetterquist, Robert, A1 aShi, Leming1 aShi, Wei1 aSmyth, Gordon, K1 aStralis-Pavese, Nancy1 aSu, Zhenqiang1 aTong, Weida1 aWang, Charles1 aWang, Jian1 aXu, Joshua1 aYe, Zhan1 aYang, Yong1 aYu, Ying1 aSalit, Marc uhttp://www.nature.com/ncomms/2014/140925/ncomms6125/full/ncomms6125.html02249nas a2200313 4500008004100000022001400041245008200055210006900137260001600206300000800222490000600230520134100236653002201577653001201599653001501611653002001626100003001646700001901676700001901695700001601714700002001730700001901750700001901769700002401788700002401812700002001836700002101856856005801877 2014 eng d a1752-050900aUnderstanding disease mechanisms with models of signaling pathway activities.0 aUnderstanding disease mechanisms with models of signaling pathwa c2014 Oct 25 a1210 v83 aBackgroundUnderstanding the aspects of the cell functionality that account for disease or drug action mechanisms is one of the main challenges in the analysis of genomic data and is on the basis of the future implementation of precision medicine.ResultsHere we propose a simple probabilistic model in which signaling pathways are separated into elementary sub-pathways or signal transmission circuits (which ultimately trigger cell functions) and then transforms gene expression measurements into probabilities of activation of such signal transmission circuits. Using this model, differential activation of such circuits between biological conditions can be estimated. Thus, circuit activation statuses can be interpreted as biomarkers that discriminate among the compared conditions. This type of mechanism-based biomarkers accounts for cell functional activities and can easily be associated to disease or drug action mechanisms. The accuracy of the proposed model is demonstrated with simulations and real datasets.ConclusionsThe proposed model provides detailed information that enables the interpretation disease mechanisms as a consequence of the complex combinations of altered gene expression values. Moreover, it offers a framework for suggesting possible ways of therapeutic intervention in a pathologically perturbed system.10aDisease mechanism10apathway10asignalling10aSystems biology1 aSebastián-Leon, Patricia1 aVidal, Enrique1 aMinguez, Pablo1 aConesa, Ana1 aTarazona, Sonia1 aAmadoz, Alicia1 aArmero, Carmen1 aSalavert, Francisco1 aVidal-Puig, Antonio1 aMontaner, David1 aDopazo, Joaquín uhttp://www.biomedcentral.com/1752-0509/8/121/abstract02998nas a2200349 4500008004100000022001400041245015500055210006900210260000900279300001100288490000600299520188000305100002102185700001902206700001702225700002002242700002402262700002202286700002802308700002102336700002002357700002102377700002102398700002302419700002902442700001602471700001802487700002102505700002402526700001902550856007902569 2012 eng d a1932-620300aDevelopment, Characterization and Experimental Validation of a Cultivated Sunflower (Helianthus annuus L.) Gene Expression Oligonucleotide Microarray.0 aDevelopment Characterization and Experimental Validation of a Cu c2012 ae458990 v73 aOligonucleotide-based microarrays with accurate gene coverage represent a key strategy for transcriptional studies in orphan species such as sunflower, H. annuus L., which lacks full genome sequences. The goal of this study was the development and functional annotation of a comprehensive sunflower unigene collection and the design and validation of a custom sunflower oligonucleotide-based microarray. A large scale EST (>130,000 ESTs) curation, assembly and sequence annotation was performed using Blast2GO (www.blast2go.de). The EST assembly comprises 41,013 putative transcripts (12,924 contigs and 28,089 singletons). The resulting Sunflower Unigen Resource (SUR version 1.0) was used to design an oligonucleotide-based Agilent microarray for cultivated sunflower. This microarray includes a total of 42,326 features: 1,417 Agilent controls, 74 control probes for sunflower replicated 10 times (740 controls) and 40,169 different non-control probes. Microarray performance was validated using a model experiment examining the induction of senescence by water deficit. Pre-processing and differential expression analysis of Agilent microarrays was performed using the Bioconductor limma package. The analyses based on p-values calculated by eBayes (p<0.01) allowed the detection of 558 differentially expressed genes between water stress and control conditions; from these, ten genes were further validated by qPCR. Over-represented ontologies were identified using FatiScan in the Babelomics suite. This work generated a curated and trustable sunflower unigene collection, and a custom, validated sunflower oligonucleotide-based microarray using Agilent technology. Both the curated unigene collection and the validated oligonucleotide microarray provide key resources for sunflower genome analysis, transcriptional studies, and molecular breeding for crop improvement.1 aFernandez, Paula1 aSoria, Marcelo1 aBlesa, David1 aDirienzo, Julio1 aMoschen, Sebastián1 aRivarola, Máximo1 aClavijo, Bernardo, Jose1 aGonzalez, Sergio1 aPeluffo, Lucila1 aPríncipi, Dario1 aDosio, Guillermo1 aAguirrezabal, Luis1 aGarcia-Garcia, Francisco1 aConesa, Ana1 aHopp, Esteban1 aDopazo, Joaquín1 aHeinz, Ruth, Amelia1 aPaniego, Norma uhttp://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.004589902782nas a2200253 4500008004100000022001400041245015200055210006900207260001600276520178700292100002502079700002602104700002902130700003102159700002802190700002602218700002802244700002702272700003302299700002702332700001602359700002902375856012402404 2012 eng d a1097-021500aExpression profiling shows differential molecular pathways and provides potential new diagnostic biomarkers for colorectal serrated adenocarcinoma.0 aExpression profiling shows differential molecular pathways and p c2012 Jun 143 aSerrated adenocarcinoma (SAC) is a recently recognized colorectal cancer (CRC) subtype accounting for 7.5-8.7% of CRCs. It has been shown that SAC has a poorer prognosis and has different molecular and immunohistochemical features compared to conventional carcinoma (CC) but, to date, only one previous study has analysed its mRNA expression profile by microarray. Using a different microarray platform, we have studied the molecular signature of 11 SACs and compared it with that of 15 matched CC with the aim of discerning the functions which characterize SAC biology and validating, at the mRNA and protein level, the most differentially expressed genes which were also tested using a validation set of 70 SACs and 70 CCs to assess their diagnostic and prognostic values. Microarray data showed a higher representation of morphogenesis-, hypoxia-, cytoskeleton- and vesicle transport-related functions and also an over-expression of fascin1 (actin-bundling protein associated with invasion) and the antiapoptotic gene hippocalcin in SAC all of which were validated both by qPCR and immunohistochemistry. Fascin1 expression was statistically associated with KRAS mutation with 88.6% sensitivity and 85.7% specificity for SAC diagnosis and the positivity of fascin1 or hippocalcin was highly suggestive of SAC diagnosis (sensitivity=100%). Evaluation of these markers in CRCs showing histological and molecular characteristics of high-level microsatellite instability (MSI-H) also helped to distinguish SACs from MSI-H CRCs. Molecular profiling demonstrates that SAC shows activation of distinct signalling pathways and that immunohistochemical fascin1 and hippocalcin expression can be reliably used for its differentiation from other CRC subtypes. © 2012 Wiley Periodicals, Inc.1 aConesa-Zamora, Pablo1 aGarcía-Solano, José1 aGarcia-Garcia, Francisco1 aTurpin, María, Del Carmen1 aTrujillo-Santos, Javier1 aTorres-Moreno, Daniel1 aOviedo-Ramírez, Isabel1 aCarbonell-Muñoz, Rosa1 aMuñoz-Delgado, Encarnación1 aRodriguez-Braun, Edith1 aConesa, Ana1 aPérez-Guillermo, Miguel uhttp://clinbioinfosspa.es/content/expression-profiling-shows-differential-molecular-pathways-and-provides-potential-new03418nas a2200253 4500008004100000022001400041245011200055210006900167260000900236300000800245490000700253520257000260100002502830700003202855700001602887700001702903700002102920700002502941700002202966700001802988700002203006700001803028856011803046 2012 eng d a1471-216400aIdentification of yeast genes that confer resistance to chitosan oligosaccharide (COS) using chemogenomics.0 aIdentification of yeast genes that confer resistance to chitosan c2012 a2670 v133 aBACKGROUND: Chitosan oligosaccharide (COS), a deacetylated derivative of chitin, is an abundant, and renewable natural polymer. COS has higher antimicrobial properties than chitosan and is presumed to act by disrupting/permeabilizing the cell membranes of bacteria, yeast and fungi. COS is relatively non-toxic to mammals. By identifying the molecular and genetic targets of COS, we hope to gain a better understanding of the antifungal mode of action of COS. RESULTS: Three different chemogenomic fitness assays, haploinsufficiency (HIP), homozygous deletion (HOP), and multicopy suppression (MSP) profiling were combined with a transcriptomic analysis to gain insight in to the mode of action and mechanisms of resistance to chitosan oligosaccharides. The fitness assays identified 39 yeast deletion strains sensitive to COS and 21 suppressors of COS sensitivity. The genes identified are involved in processes such as RNA biology (transcription, translation and regulatory mechanisms), membrane functions (e.g. signalling, transport and targeting), membrane structural components, cell division, and proteasome processes. The transcriptomes of control wild type and 5 suppressor strains overexpressing ARL1, BCK2, ERG24, MSG5, or RBA50, were analyzed in the presence and absence of COS. Some of the up-regulated transcripts in the suppressor overexpressing strains exposed to COS included genes involved in transcription, cell cycle, stress response and the Ras signal transduction pathway. Down-regulated transcripts included those encoding protein folding components and respiratory chain proteins. The COS-induced transcriptional response is distinct from previously described environmental stress responses (i.e. thermal, salt, osmotic and oxidative stress) and pre-treatment with these well characterized environmental stressors provided little or any resistance to COS. CONCLUSIONS: Overexpression of the ARL1 gene, a member of the Ras superfamily that regulates membrane trafficking, provides protection against COS-induced cell membrane permeability and damage. We found that the ARL1 COS-resistant over-expression strain was as sensitive to Amphotericin B, Fluconazole and Terbinafine as the wild type cells and that when COS and Fluconazole are used in combination they act in a synergistic fashion. The gene targets of COS identified in this study indicate that COS’s mechanism of action is different from other commonly studied fungicides that target membranes, suggesting that COS may be an effective fungicide for drug-resistant fungal pathogens.1 aJaime, María, D L A1 aLopez-Llorca, Luis, Vicente1 aConesa, Ana1 aLee, Anna, Y1 aProctor, Michael1 aHeisler, Lawrence, E1 aGebbia, Marinella1 aGiaever, Guri1 aWestwood, Timothy1 aNislow, Corey uhttp://clinbioinfosspa.es/content/identification-yeast-genes-confer-resistance-chitosan-oligosaccharide-cos-using01733nas a2200193 4500008004100000022001400041245017100055210006900226260001600295520097200311100001801283700001601301700001801317700002101335700001801356700002201374700001801396856012501414 2012 eng d a1364-370300aMicroarray analysis of Etrog citron (Citrus medica L.) reveals changes in chloroplast, cell wall, peroxidase and symporter activities in response to viroid infection.0 aMicroarray analysis of Etrog citron Citrus medica L reveals chan c2012 Mar 153 aViroids are small (246-401 nucleotides), single-stranded, circular RNA molecules that infect several crop plants and can cause diseases of economic importance. Citrus are the hosts in which the largest number of viroids have been identified. Citrus exocortis viroid (CEVd), the causal agent of citrus exocortis disease, induces considerable losses in citrus crops. Changes in the gene expression profile during the early (pre-symptomatic) and late (post-symptomatic) stages of Etrog citron infected with CEVd were investigated using a citrus cDNA microarray. MaSigPro analysis was performed and, on the basis of gene expression profiles as a function of the time after infection, the differentially expressed genes were classified into five clusters. FatiScan analysis revealed significant enrichment of functional categories for each cluster, indicating that viroid infection triggers important changes in chloroplast, cell wall, peroxidase and symporter activities.1 aRizza, Serena1 aConesa, Ana1 aJuarez, José1 aCatara, Antonino1 aNavarro, Luis1 aDuran-Vila, Nuria1 aAncillo, Gema uhttp://clinbioinfosspa.es/content/microarray-analysis-etrog-citron-citrus-medica-l-reveals-changes-chloroplast-cell-wall01929nas a2200253 4500008004100000022001400041245006800055210006500123260001600188300001100204490000700215520118200222653000801404100003001412700002901442700002101471700001801492700001801510700002001528700002101548700002101569700001601590856006901606 2012 eng d a1367-481100aQualimap: evaluating next-generation sequencing alignment data.0 aQualimap evaluating nextgeneration sequencing alignment data c2012 Oct 15 a2678-90 v283 aMOTIVATION: The sequence alignment/map (SAM) and the binary alignment/map (BAM) formats have become the standard method of representation of nucleotide sequence alignments for next-generation sequencing data. SAM/BAM files usually contain information from tens to hundreds of millions of reads. Often, the sequencing technology, protocol and/or the selected mapping algorithm introduce some unwanted biases in these data. The systematic detection of such biases is a non-trivial task that is crucial to drive appropriate downstream analyses. RESULTS: We have developed Qualimap, a Java application that supports user-friendly quality control of mapping data, by considering sequence features and their genomic properties. Qualimap takes sequence alignment data and provides graphical and statistical analyses for the evaluation of data. Such quality-control data are vital for highlighting problems in the sequencing and/or mapping processes, which must be addressed prior to further analyses. AVAILABILITY: Qualimap is freely available from http://www.qualimap.org. CONTACT: aconesa@cipf.es SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.10aNGS1 aGarcía-Alcalde, Fernando1 aOkonechnikov, Konstantin1 aCarbonell, José1 aCruz, Luis, M1 aGötz, Stefan1 aTarazona, Sonia1 aDopazo, Joaquín1 aMeyer, Thomas, F1 aConesa, Ana uhttp://bioinformatics.oxfordjournals.org/content/28/20/2678.long03639nas a2200505 4500008004100000022001400041245012700055210006900182260000900251300001100260490000600271520212800277653001902405653001202424653002302436653001802459653002602477653001802503653000802521653001502529653002202544653003002566653002302596653001002619653002402629653002802653653000902681653002202690653001302712653001702725653001802742100001902760700001802779700002102797700001402818700001602832700002402848700002202872700002102894700002202915700001802937700001702955700003002972856013103002 2012 eng d a1932-620300aTranscriptome profiling of the intoxication response of Tenebrio molitor larvae to Bacillus thuringiensis Cry3Aa protoxin.0 aTranscriptome profiling of the intoxication response of Tenebrio c2012 ae346240 v73 aBacillus thuringiensis (Bt) crystal (Cry) proteins are effective against a select number of insect pests, but improvements are needed to increase efficacy and decrease time to mortality for coleopteran pests. To gain insight into the Bt intoxication process in Coleoptera, we performed RNA-Seq on cDNA generated from the guts of Tenebrio molitor larvae that consumed either a control diet or a diet containing Cry3Aa protoxin. Approximately 134,090 and 124,287 sequence reads from the control and Cry3Aa-treated groups were assembled into 1,318 and 1,140 contigs, respectively. Enrichment analyses indicated that functions associated with mitochondrial respiration, signalling, maintenance of cell structure, membrane integrity, protein recycling/synthesis, and glycosyl hydrolases were significantly increased in Cry3Aa-treated larvae, whereas functions associated with many metabolic processes were reduced, especially glycolysis, tricarboxylic acid cycle, and fatty acid synthesis. Microarray analysis was used to evaluate temporal changes in gene expression after 6, 12 or 24 h of Cry3Aa exposure. Overall, microarray analysis indicated that transcripts related to allergens, chitin-binding proteins, glycosyl hydrolases, and tubulins were induced, and those related to immunity and metabolism were repressed in Cry3Aa-intoxicated larvae. The 24 h microarray data validated most of the RNA-Seq data. Of the three intoxication intervals, larvae demonstrated more differential expression of transcripts after 12 h exposure to Cry3Aa. Gene expression examined by three different methods in control vs. Cry3Aa-treated larvae at the 24 h time point indicated that transcripts encoding proteins with chitin-binding domain 3 were the most differentially expressed in Cry3Aa-intoxicated larvae. Overall, the data suggest that T. molitor larvae mount a complex response to Cry3Aa during the initial 24 h of intoxication. Data from this study represent the largest genetic sequence dataset for T. molitor to date. Furthermore, the methods in this study are useful for comparative analyses in organisms lacking a sequenced genome.10aAdministration10aAnimals10aBacterial Proteins10aBase Sequence10aBiosynthetic Pathways10aComplementary10aDNA10aEndotoxins10aEnergy Metabolism10aGene Expression Profiling10aHemolysin Proteins10aLarva10aMicroarray Analysis10aMolecular Sequence Data10aOral10aSequence Analysis10aTenebrio10aTime Factors10aTranscriptome1 aOppert, Brenda1 aDowd, Scot, E1 aBouffard, Pascal1 aLi, Lewyn1 aConesa, Ana1 aLorenzen, Marcé, D1 aToutges, Michelle1 aMarshall, Jeremy1 aHuestis, Diana, L1 aFabrick, Jeff1 aOppert, Cris1 aJurat-Fuentes, Juan, Luis uhttp://clinbioinfosspa.es/content/transcriptome-profiling-intoxication-response-tenebrio-molitor-larvae-bacillus-thuringiensis02754nas a2200217 4500008004100000022001400041245012800055210006900183260000900252300000700261490000600268520203200274100002702306700003302333700003002366700002902396700002002425700001602445700001802461856005702479 2012 eng d a2193-180100aTransdifferentiation of MALME-3M and MCF-7 Cells toward Adipocyte-like Cells is Dependent on Clathrin-mediated Endocytosis.0 aTransdifferentiation of MALME3M and MCF7 Cells toward Adipocytel c2012 a440 v13 aABSTRACT: Enforced cell transdifferentiation of human cancer cells is a promising alternative to conventional chemotherapy. We previously identified albumin-associated lipid- and, more specifically, saturated fatty acid-induced transdifferentiation programs in human cancer cells (HCCLs). In this study, we further characterized the adipocyte-like cells, resulting from the transdifferentiation of human cancer cell lines MCF-7 and MALME-3M, and proposed a common mechanistic approach for these transdifferentiating programs. We showed the loss of pigmentation in MALME-3M cells treated with albumin-associated lipids, based on electron microscopic analysis, and the overexpression of perilipin 2 (PLIN2) by western blotting in MALME-3M and MCF-7 cells treated with unsaturated fatty acids. Comparing the gene expression profiles of naive melanoma MALME-3M cells and albumin-associated lipid-treated cells, based on RNA sequencing, we confirmed the transcriptional upregulation of some key adipogenic gene markers and also an alternative splicing of the adipogenic master regulator PPARG, that is probably related to the reported up regulated expression of the protein. Most importantly, these results also showed the upregulation of genes responsible for Clathrin (CLTC) and other adaptor-related proteins. An increase in CLTC expression in the transdifferentiated cells was confirmed by western blotting. Inactivation of CLTC by chlorpromazine (CHP), an inhibitor of CTLC mediated endocytosis (CME), and gene silencing by siRNAs, partially reversed the accumulation of neutral lipids observed in the transdifferentiated cells. These findings give a deeper insight into the phenotypic changes observed in HCCL to adipocyte-like transdifferentiation and point towards CME as a key pathway in distinct transdifferentiation programs. DISCLOSURES: Simon C and Aguilar-Gallardo C are co-inventors of the International Patent Application No. PCT/EP2011/004941 entitled "Methods for tumor treatment and adipogenesis differentiation".1 aCarcel-Trullols, Jaime1 aAguilar-Gallardo, Cristóbal1 aGarcía-Alcalde, Fernando1 aPardo-Cea, Miguel, Angel1 aDopazo, Joaquin1 aConesa, Ana1 aSimon, Carlos uhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3725915/03135nas a2200145 4500008004100000022001400041245012900055210006900184260001600253520254200269100002002811700002002831700001602851856012202867 2011 eng d a1468-435700aARSyN: a method for the identification and removal of systematic noise in multifactorial time course microarray experiments.0 aARSyN a method for the identification and removal of systematic  c2011 Nov 143 aTranscriptomic profiling experiments that aim to the identification of responsive genes in specific biological conditions are commonly set up under defined experimental designs that try to assess the effects of factors and their interactions on gene expression. Data from these controlled experiments, however, may also contain sources of unwanted noise that can distort the signal under study, affect the residuals of applied statistical models, and hamper data analysis. Commonly, normalization methods are applied to transcriptomics data to remove technical artifacts, but these are normally based on general assumptions of transcript distribution and greatly ignore both the characteristics of the experiment under consideration and the coordinative nature of gene expression. In this paper, we propose a novel methodology, ARSyN, for the preprocessing of microarray data that takes into account these 2 last aspects. By combining analysis of variance (ANOVA) modeling of gene expression values and multivariate analysis of estimated effects, the method identifies the nonstructured part of the signal associated to the experimental factors (the noise within the signal) and the structured variation of the ANOVA errors (the signal of the noise). By removing these noise fractions from the original data, we create a filtered data set that is rich in the information of interest and includes only the random noise required for inferential analysis. In this work, we focus on multifactorial time course microarray (MTCM) experiments with 2 factors: one quantitative such as time or dosage and the other qualitative, as tissue, strain, or treatment. However, the method can be used in other situations such as experiments with only one factor or more complex designs with more than 2 factors. The filtered data obtained after applying ARSyN can be further analyzed with the appropriate statistical technique to obtain the biological information required. To evaluate the performance of the filtering strategy, we have applied different statistical approaches for MTCM analysis to several real and simulated data sets, studying also the efficiency of these techniques. By comparing the results obtained with the original and ARSyN filtered data and also with other filtering techniques, we can conclude that the proposed method increases the statistical power to detect biological signals, especially in cases where there are high levels of structural noise. Software for ARSyN is freely available at http://www.ua.es/personal/mj.nueda.1 aNueda, Maria, J1 aFerrer, Alberto1 aConesa, Ana uhttp://clinbioinfosspa.es/content/arsyn-method-identification-and-removal-systematic-noise-multifactorial-time-course02485nas a2200229 4500008004100000245005800041210005500099260001600154300001200170490000700182520178000189100001801969700001901987700003002006700003102036700002202067700002202089700002102111700001902132700001602151856008802167 2011 eng d00aB2G-FAR, a species centered GO annotation repository.0 aB2GFAR a species centered GO annotation repository c2011 Feb 18 a919-9240 v273 a

MOTIVATION: Functional genomics research has expanded enormously in the last decade thanks to the cost-reduction in high-throughput technologies and the development of computational tools that generate, standardize and share information on gene and protein function such as the Gene Ontology (GO). Nevertheless many biologists, especially working with non-model organisms, still suffer from non-existing or low coverage functional annotation, or simply struggle retrieving, summarizing and querying these data. RESULTS: The Blast2GO Functional Annotation Repository (B2G-FAR) is a bioinformatics resource envisaged to provide functional information for otherwise uncharacterized sequence-data and offers data-mining tools to analyze a larger repertoire of species than currently available. This new annotation resource has been created by applying the Blast2GO functional annotation engine in a strongly high-throughput manner to the entire space of public available sequences. The resulting repository contains GO term predictions for over 13.2 million non-redundant protein sequences based on BLAST search alignments from the SIMAP database. We generated GO annotation for approximately 150.000 different taxa making available the 2000 species with the highest coverage through B2G-FAR. A second section within B2G-FAR holds functional annotations for 17 non-model organism Affymetrix GeneChips. Conclusions: B2G-FAR provides easy access to exhaustive functional annotation for 2000 species offering a good balance between quality and quantity, thereby supporting functional genomics research especially in the case of non-model organisms. AVAILABILITY: The annotation resource is available at http://b2gfar.bioinfo.cipf.es. CONTACT: aconesa@cipf.es, sgoetz@cipf.es.

1 aGötz, Stefan1 aArnold, Roland1 aSebastián-Leon, Patricia1 aMartín-Rodríguez, Samuel1 aTischler, Patrick1 aJehl, Marc-André1 aDopazo, Joaquín1 aRattei, Thomas1 aConesa, Ana uhttp://clinbioinfosspa.es/content/b2g-far-species-centered-go-annotation-repository00689nas a2200193 4500008004100000022001400041245010000055210006900155260000900224300000800233490000700241520001400248100002100262700002600283700001600309700002000325700002100345856012900366 2011 eng d a1471-222900aFortunella margarita Transcriptional Reprogramming Triggered by Xanthomonas citri subsp. citri.0 aFortunella margarita Transcriptional Reprogramming Triggered by  c2011 a1590 v113 aABSTRACT:1 aKhalaf, Abeer, A1 aGmitter, Frederick, G1 aConesa, Ana1 aDopazo, Joaquin1 aMoore, Gloria, A uhttp://clinbioinfosspa.es/content/fortunella-margarita-transcriptional-reprogramming-triggered-xanthomonas-citri-subsp-citri02018nas a2200157 4500008004100000245013700041210006900178260001500247520137300262100001801635700001601653700002101669700002701690700001801717856012501735 2011 eng d00aHistone modifications and expression of DAM6 gene in peach are modulated during bud dormancy release in a cultivar-dependent manner.0 aHistone modifications and expression of DAM6 gene in peach are m c2011 Sep 73 a

• Bud dormancy release in many woody perennial plants responds to the seasonal accumulation of chilling stimulus. MADS-box transcription factors encoded by DORMANCY ASSOCIATED MADS-box (DAM) genes in peach (Prunus persica) are implicated in this pathway, but other regulatory factors remain to be identified. In addition, the regulation of DAM gene expression is not well known at the molecular level. • A microarray hybridization approach was performed to identify genes whose expression correlates with the bud dormancy-related behaviour in 10 different peach cultivars. Histone modifications in DAM6 gene were investigated by chromatin immunoprecipitation in two different cultivars. • The expression of DAM4-DAM6 and several genes related to abscisic acid and drought stress response correlated with the dormancy behaviour of peach cultivars. The trimethylation of histone H3 at K27 in the DAM6 promoter, coding region and the second large intron was preceded by a decrease in acetylated H3 and trimethylated H3K4 in the region of translation start, coinciding with repression of DAM6 during dormancy release. • Analysis of chromatin modifications reinforced the role of epigenetic mechanisms in DAM6 regulation and bud dormancy release, and highlighted common features with the vernalization process in Arabidopsis thaliana and cereals.

1 aLeida, Carmen1 aConesa, Ana1 aLlácer, Gerardo1 aBadenes, María, Luisa1 aRíos, Gabino uhttp://clinbioinfosspa.es/content/histone-modifications-and-expression-dam6-gene-peach-are-modulated-during-bud-dormancy01038nas a2200229 4500008004100000245010000041210006900141260001300210300001100223490000700234520022900241100002600470700002500496700002500521700002200546700002300568700003700591700002200628700001600650700001800666856012400684 2011 eng d00aModeling human endometrial decidualization from the interaction between proteome and secretome.0 aModeling human endometrial decidualization from the interaction  c2011 Mar a706-160 v963 a

Decidualization of the human endometrium, which involves morphological and biochemical modifications of the endometrial stromal cells (ESCs), is a prerequisite for adequate trophoblast invasion and placenta formation.

1 aGarrido-Gomez, Tamara1 aDominguez, Francisco1 aLopez, Juan, Antonio1 aCamafeita, Emilio1 aQuiñonero, Alicia1 aMartinez-Conejero, Jose, Antonio1 aPellicer, Antonio1 aConesa, Ana1 aSimon, Carlos uhttp://clinbioinfosspa.es/content/modeling-human-endometrial-decidualization-interaction-between-proteome-and-secretome01129nas a2200169 4500008004100000245010300041210006900144260001500213300001000228490000700238520049600245100003000741700002900771700002100800700001600821856012200837 2011 eng d00aPaintomics: a web based tool for the joint visualization of transcriptomics and metabolomics data.0 aPaintomics a web based tool for the joint visualization of trans c2011 Jan 1 a137-90 v273 a

The development of the omics technologies such as transcriptomics, proteomics and metabolomics has made possible the realization of systems biology studies where biological systems are interrogated at different levels of biochemical activity (gene expression, protein activity and/or metabolite concentration). An effective approach to the analysis of these complex datasets is the joined visualization of the disparate biomolecular data on the framework of known biological pathways.

1 aGarcía-Alcalde, Fernando1 aGarcía-López, Federico1 aDopazo, Joaquín1 aConesa, Ana uhttp://clinbioinfosspa.es/content/paintomics-web-based-tool-joint-visualization-transcriptomics-and-metabolomics-data01322nas a2200265 4500008004100000245009000041210006900131260000900200300000800209490000700217520047300224100001800697700001900715700002100734700001900755700002600774700002600800700001800826700001600844700002500860700002100885700001600906700002100922856011300943 2011 eng d00aProfiling the venom gland transcriptomes of Costa Rican snakes by 454 pyrosequencing.0 aProfiling the venom gland transcriptomes of Costa Rican snakes b c2011 a2590 v123 a

A long term research goal of venomics, of applied importance for improving current antivenom therapy, but also for drug discovery, is to understand the pharmacological potential of venoms. Individually or combined, proteomic and transcriptomic studies have demonstrated their feasibility to explore in depth the molecular diversity of venoms. In the absence of genome sequence, transcriptomes represent also valuable searchable databases for proteomic projects.

1 aDurban, Jordi1 aJuárez, Paula1 aAngulo, Yamileth1 aLomonte, Bruno1 aFlores-Diaz, Marietta1 aAlape-Girón, Alberto1 aSasa, Mahmood1 aSanz, Libia1 aGutiérrez, José, M1 aDopazo, Joaquín1 aConesa, Ana1 aCalvete, Juan, J uhttp://clinbioinfosspa.es/content/profiling-venom-gland-transcriptomes-costa-rican-snakes-454-pyrosequencing02554nas a2200361 4500008004100000245014100041210006900182260001600251300003100267490000700298520145100305653001501756653002001771653001501791653001001806653000801816653000901824100002001833700002101853700001701874700002101891700001801912700001601930700002301946700002901969700002701998700002002025700002302045700002002068700002002088700002102108856006302129 2010 eng d00aBabelomics: an integrative platform for the analysis of transcriptomics, proteomics and genomic data with advanced functional profiling.0 aBabelomics an integrative platform for the analysis of transcrip c2010 May 16 aW210-W213. Featured in NAR0 v383 a

Babelomics is a response to the growing necessity of integrating and analyzing different types of genomic data in an environment that allows an easy functional interpretation of the results. Babelomics includes a complete suite of methods for the analysis of gene expression data that include normalization (covering most commercial platforms), pre-processing, differential gene expression (case-controls, multiclass, survival or continuous values), predictors, clustering; large-scale genotyping assays (case controls and TDTs, and allows population stratification analysis and correction). All these genomic data analysis facilities are integrated and connected to multiple options for the functional interpretation of the experiments. Different methods of functional enrichment or gene set enrichment can be used to understand the functional basis of the experiment analyzed. Many sources of biological information, which include functional (GO, KEGG, Biocarta, Reactome, etc.), regulatory (Transfac, Jaspar, ORegAnno, miRNAs, etc.), text-mining or protein-protein interaction modules can be used for this purpose. Finally a tool for the de novo functional annotation of sequences has been included in the system. This provides support for the functional analysis of non-model species. Mirrors of Babelomics or command line execution of their individual components are now possible. Babelomics is available at http://www.babelomics.org.

10ababelomics10agene expression10agenotyping10agepas10aGSA10aGWAS1 aMedina, Ignacio1 aCarbonell, José1 aPulido, Luis1 aMadeira, Sara, C1 aGoetz, Stefan1 aConesa, Ana1 aTárraga, Joaquín1 aPascual-Montano, Alberto1 aNogales-Cadenas, Ruben1 aSantoyo, Javier1 aGarcía, Francisco1 aMarbà, Martina1 aMontaner, David1 aDopazo, Joaquín uhttp://nar.oxfordjournals.org/content/38/suppl_2/W210.full01700nas a2200265 4500008004100000245004500041210004400086260000900130300001300139490000600152520096600158653000801124653001401132100002001146700001601166700002701182700002001209700002001229700002301249700001901272700001901291700002001310700002001330856008401350 2010 eng d00aInitial genomics of the human nucleolus.0 aInitial genomics of the human nucleolus c2010 ae10008890 v63 a

We report for the first time the genomics of a nuclear compartment of the eukaryotic cell. 454 sequencing and microarray analysis revealed the pattern of nucleolus-associated chromatin domains (NADs) in the linear human genome and identified different gene families and certain satellite repeats as the major building blocks of NADs, which constitute about 4% of the genome. Bioinformatic evaluation showed that NAD-localized genes take part in specific biological processes, like the response to other organisms, odor perception, and tissue development. 3D FISH and immunofluorescence experiments illustrated the spatial distribution of NAD-specific chromatin within interphase nuclei and its alteration upon transcriptional changes. Altogether, our findings describe the nature of DNA sequences associated with the human nucleolus and provide insights into the function of the nucleolus in genome organization and establishment of nuclear architecture.

10aNGS10anucleolus1 aNémeth, Attila1 aConesa, Ana1 aSantoyo-López, Javier1 aMedina, Ignacio1 aMontaner, David1 aPéterfia, Bálint1 aSolovei, Irina1 aCremer, Thomas1 aDopazo, Joaquin1 aLängst, Gernot uhttp://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.100088902240nas a2200217 4500008004100000245012100041210007100162260001300233300001100246490000700257520147000264100001901734700002201753700001801775700002201793700002001815700001901835700001601854700002301870856012901893 2010 eng d00aSIMAP–a comprehensive database of pre-calculated protein sequence similarities, domains, annotations and clusters.0 aSIMAP–a comprehensive database of precalculated protein sequence c2010 Jan aD223-60 v383 a

The prediction of protein function as well as the reconstruction of evolutionary genesis employing sequence comparison at large is still the most powerful tool in sequence analysis. Due to the exponential growth of the number of known protein sequences and the subsequent quadratic growth of the similarity matrix, the computation of the Similarity Matrix of Proteins (SIMAP) becomes a computational intensive task. The SIMAP database provides a comprehensive and up-to-date pre-calculation of the protein sequence similarity matrix, sequence-based features and sequence clusters. As of September 2009, SIMAP covers 48 million proteins and more than 23 million non-redundant sequences. Novel features of SIMAP include the expansion of the sequence space by including databases such as ENSEMBL as well as the integration of metagenomes based on their consistent processing and annotation. Furthermore, protein function predictions by Blast2GO are pre-calculated for all sequences in SIMAP and the data access and query functions have been improved. SIMAP assists biologists to query the up-to-date sequence space systematically and facilitates large-scale downstream projects in computational biology. Access to SIMAP is freely provided through the web portal for individuals (http://mips.gsf.de/simap/) and for programmatic access through DAS (http://webclu.bio.wzw.tum.de/das/) and Web-Service (http://mips.gsf.de/webservices/services/SimapService2.0?wsdl).

1 aRattei, Thomas1 aTischler, Patrick1 aGötz, Stefan1 aJehl, Marc-André1 aHoser, Jonathan1 aArnold, Roland1 aConesa, Ana1 aMewes, Hans-Werner uhttp://clinbioinfosspa.es/content/simap%E2%80%93-comprehensive-database-pre-calculated-protein-sequence-similarities-domains00704nas a2200181 4500008004100000022001400041245013200055210006900187300000800256490000600264100002600270700001600296700001800312700002000330700002200350700001900372856013100391 2009 eng d a1756-050000aParallel changes in gene expression in peripheral blood mononuclear cells and the brain after maternal separation in the mouse.0 aParallel changes in gene expression in peripheral blood mononucl a1950 v21 avan Heerden, Johan, H1 aConesa, Ana1 aStein, Dan, J1 aMontaner, David1 aRussell, Vivienne1 aIlling, Nicola uhttp://clinbioinfosspa.es/content/parallel-changes-gene-expression-peripheral-blood-mononuclear-cells-and-brain-after-maternal