Carlos Tejero Prieto

The minimum information required for reporting a molecular interaction experiment (MIMIx)

A wealth of molecular interaction data is available in the literature, ranging from large-scale datasets to a single interaction confirmed by several different techniques. These data are all too often reported either as free text or in tables of variable format, and are often missing key pieces of information essential for a full understanding of the experiment. Here we propose MIMIx, the minimum information required for reporting a molecular interaction experiment. Adherence to these reporting guidelines will result in publications of increased clarity and usefulness to the scientific community and will support the rapid, systematic capture of molecular interaction data in public databases, thereby improving access to valuable interaction data.

PSICQUIC and PSISCORE: accessing and scoring molecular interactions

To study proteins in the context of a cellular system, it is essential that the molecules with which a protein interacts are identified and the functional consequence of each interaction is understood. A plethora of resources now exist to capture molecular interaction data from the many laboratories generating…

Cross-talk of global nutritional regulators in the control of primary and secondary metabolism in Streptomyces.

Limitation of different nutrients in Streptomyces coelicolor A3(2) triggers nutrient‐stress responses, mediated by PhoP, GlnR, AfsR and other regulators, that are integrated at the molecular level and control secondary metabolite biosynthesis and differentiation. In addition, utilization of chitin or N‐acetylglucosamine regulates secondary metabolite biosynthesis by a mechanism mediated by DasR. Phosphate control of primary and secondary metabolism in Streptomyces species is mediated by the two‐component PhoR–PhoP system. In S. coelicolor, PhoP controls secondary metabolism by binding to a PHO box in the afsS promoter overlapping with the AfsR binding site. Therefore, the afsS promoter serves to integrate the PhoP‐mediated response to phosphate limitation and AfsR‐mediated responses to other unknown environmental stimuli. Interestingly, phosphate control oversees nitrogen regulation but not vice versa. In ΔphoP mutants, expression of some nitrogen metabolism genes including glnA, glnII and glnK is increased. Phosphate control of these genes is exerted through binding of PhoP to the promoters of glnR (the global nitrogen regulator), glnA, glnII and the amtB–glnK–glnD operon. This regulation allows a ‘metabolic homeostasis’ of phosphate and nitrogen utilization pathways, preventing nutritional unbalances. Similar mechanisms of interaction between phosphate control and carbon catabolite regulation or between phosphate and DasR‐mediated N‐acetylglucosamine regulation appear to exist. Transport of N‐acetylglucosamine by the NagE2 permease and, therefore, regulation of secondary metabolism, is dependent upon the balance of phosphorylated/dephosphorylated proteins of the N‐acetylglucosamine phosphotransferase system. These findings provide the bases for understanding the mechanisms underlying systems biology of Streptomyces species.

APID interactomes: providing proteome-based interactomes with controlled quality for multiple species and derived networks

APID (Agile Protein Interactomes DataServer) is an interactive web server that provides unified generation and delivery of protein interactomes mapped to their respective proteomes. This resource is a new, fully redesigned server that includes a comprehensive collection of protein interactomes for more than 400 organisms (25 of which include more than 500 interactions) produced by the integration of only experimentally validated protein–protein physical interactions. For each protein–protein interaction (PPI) the server includes currently reported information about its experimental validation to allow selection and filtering at different quality levels. As a whole, it provides easy access to the interactomes from specific species and includes a global uniform compendium of 90,379 distinct proteins and 678,441 singular interactions. APID integrates and unifies PPIs from major primary databases of molecular interactions, from other specific repositories and also from experimentally resolved 3D structures of protein complexes where more than two proteins were identified. For this purpose, a collection of 8,388 structures were analyzed to identify specific PPIs. APID also includes a new graph tool (based on Cytoscape.js) for visualization and interactive analyses of PPI networks. The server does not require registration and it is freely available for use at http://apid.dep.usal.es.

Draft Genome of Streptomyces tsukubaensis NRRL 18488, the Producer of the Clinically Important Immunosuppressant Tacrolimus (FK506)

The macrocyclic polyketide tacrolimus (FK506) is a potent immunosuppressant that prevents T-cell proliferation produced solely by Streptomyces species. We report here the first draft genome sequence of a true FK506 producer, Streptomyces tsukubaensis NRRL 18488, the first tacrolimus-producing strain that was isolated and that contains the full tacrolimus biosynthesis gene cluster.

Moduli Spaces of Semistable Sheaves on Singular Genus 1 Curves

We find some equivalences of the derived category of coherent sheaves on a Gorenstein genus one curve that preserve the (semi)-stability of pure-dimensional sheaves. Using them we establish new identifications between certain Simpson moduli spaces of semistable sheaves on the curve. For rank zero, the moduli spaces are symmetric powers of the curve whilst for a fixed positive rank there are only a finite number of nonisomorphic spaces. We prove similar results for the relative semistable moduli spaces on an arbitrary genus one fibration with no conditions either on the base or on the total space. For a cycle E N of projective lines, we show that the unique degree 0 stable sheaves are the line bundles having degree 0 on every irreducible component and the sheaves supported on one irreducible component. We also prove that the connected component of the moduli space that contains vector bundles of rank r is isomorphic to the rth symmetric product of the rational curve with one node.

A CLUSTER MERGING METHOD FOR TIME SERIES MICROARRAY WITH PRODUCTION VALUES

A challenging task in time-course microarray data analysis is to cluster genes meaningfully combining the information provided by multiple replicates covering the same key time points. This paper proposes a novel cluster merging method to accomplish this goal obtaining groups with highly correlated genes. The main idea behind the proposed method is to generate a clustering starting from groups created based on individual temporal series (representing different biological replicates measured in the same time points) and merging them by taking into account the frequency by which two genes are assembled together in each clustering. The gene groups at the level of individual time series are generated using several shape-based clustering methods. This study is focused on a real-world time series microarray task with the aim to find co-expressed genes related to the production and growth of a certain bacteria. The shape-based clustering methods used at the level of individual time series rely on identifying similar gene expression patterns over time which, in some models, are further matched to the pattern of production/growth. The proposed cluster merging method is able to produce meaningful gene groups which can be naturally ranked by the level of agreement on the clustering among individual time series. The list of clusters and genes is further sorted based on the information correlation coefficient and new problem-specific relevant measures. Computational experiments and results of the cluster merging method are analyzed from a biological perspective and further compared with the clustering generated based on the mean value of time series and the same shape-based algorithm.

Fourier–Mukai and Nahm transforms for holomorphic triples on elliptic curves

Abstract We define a Fourier–Mukai transform for a triple consisting of two holomorphic vector bundles over an elliptic curve and a homomorphism between them. We prove that in some cases, the transform preserves the natural stability condition for a triple. We also define a Nahm transform for solutions to natural gauge-theoretic equations on a triple—vortices—and explore some of its basic properties. Our approach combines direct methods with dimensional reduction techniques, relating triples over a curve with vector bundles over the product of the curve with the complex projective line.

Comparative blood transcriptome analysis in idiopathic and LRRK2 G2019S–associated Parkinson's disease

Patients with Parkinsons disease (PD) carrying the G2019S mutation of the LRRK2 gene provide an opportunity of studying in a homogeneous setting the molecular pathways involved in the pathogenesis of common idiopathic forms of PD. However, whether common mechanisms are involved in both conditions in not known. Here, we compared genome-wide gene expression (RNA sequencing) in peripheral blood between PD patients carrying the G2019S mutation of the LRRK2 gene and idiopathic PD cases, to deepen in the understanding of this topic. In addition, we compared the blood transcriptome between 2 cohorts of carriers of the G2019S mutation (symptomatic and asymptomatic) and 2 cohorts of noncarriers (symptomatic and asymptomatic) for detecting transcriptomic changes attributable to the presence of the G2019S mutation. We searched for gene enrichment in Reactome or Kyoto Encyclopedia of Genes and Genomes pathways. We found that despite some overlap, peripheral blood transcriptome differs widely between idiopathic and LRRK2 G2019S-associated PD, with only 4 deregulated pathways shared by both conditions (complement and coagulation cascades, cell adhesion molecules, hematopoietic cell lineage, and extracellular matrix organization). Changes in the blood transcriptome observed in asymptomatic carriers of the mutation included 6 genes known to be associated with PD in genome-wide association studies and also pathways related with immunity. Our findings emphasize the notion that PD is likely a pathogenically heterogeneous condition and suggest the existence of specific mechanisms involved in LRRK2-associated PD.

Shape-Output Gene Clustering for Time Series Microarrays

The identification of coexpressed genes is a challenging problem in microarray data analysis due to a very high number of genes and low number of samples normally available. This paper presents a shape-output clustering method which is engaged in the analysis of a real-world time series microarray data from the industrial microbiology area. The proposed approach uses the changes in gene expression levels to group genes based on their shape measured over time in several samples. Furthermore, these coexpression patterns are correlated with the measured outputs of production and growth available for each sample. Experiments are performed for time series microarray of a bacteria and an analysis from a biological perspective is carried out. The obtained results confirm the existence of relationships between output variables and gene expressions.