Gene Expression Integration into Pathway Modules Reveals a Pan-Cancer Metabolic Landscape

BIO2014-57291-R and SAF2017-88908-R from the Spanish Ministry of Economy and Competitivenessgrant PI15/00854 from the FIS“Plataforma de Recursos Biomoleculares y Bioinformáticos” PT17/0009/0006 from the ISCIII, cofunded with European Regional Development FundsFP7-PEOPLE-2012-ITN MLPM2012EU H2020-INFRADEV-1-2015-1 ELIXIR-EXCELERAT

Models of cell signaling uncover molecular mechanisms of high-risk neuroblastoma and predict disease outcome

Spanish Ministry of Economy and Competitiveness grant BIO2014–57291-RSpanish Ministry of Economy and Competitiveness grant SAF2017–88908-R“Plataforma de Recursos Biomoleculares y Bioinformáticos” PT13/0001/0007EU H2020-INFRADEV-1-2015-1 ELIXIR-EXCELERATE (ref. 676559)EU FP7-People ITN Marie Curie Project (ref 316861)

Mechanistic modeling of the SARS-CoV-2 disease map.

Here we present a web interface that implements a comprehensive mechanistic model of the SARS-CoV-2 disease map. In this framework, the detailed activity of the human signaling circuits related to the viral infection, covering from the entry and replication mechanisms to the downstream consequences as inflammation and antigenic response, can be inferred from gene expression experiments. Moreover, the effect of potential interventions, such as knock-downs, or drug effects (currently the system models the effect of more than 8000 DrugBank drugs) can be studied. This freely available tool not only provides an unprecedentedly detailed view of the mechanisms of viral invasion and the consequences in the cell but has also the potential of becoming an invaluable asset in the search for efficient antiviral treatments

Indicación Farmacéutica para el estreñimiento en pacientes con diabetes e hipertensión arterial.

Introducción: El estreñimiento en pacientes con hipertensión arterial o diabetes es un motivo frecuente de consulta al farmacéutico. La indicación farmacéutica no debe interferir con la medicación habitual de estos pacientes. Objetivos: Formular recomendaciones sobre indicación farmacéutica a pacientes con diabetes y/o hipertensión arterial que acuden a la oficina de farmacia solicitando tratamiento farmacológico para el estreñimiento. Material y métodos: Mediante revisión sistemática de Guías de Práctica Clínica sobre abordaje del estreñimiento, se han elaborado recomendaciones sobre indicación farmacéutica a pacientes con diabetes y/o hipertensión arterial que acuden a la oficina de farmacia solicitando tratamiento farmacológico. Tras diseñar una estrategia de búsqueda, se seleccionaron las fuentes bibliográficas y se llevó a cabo la recogida de información. La búsqueda bibliográfica se realizó en los siguientes recursos web: Medline, GuíaSalud, National Guideline Clearinghouse, Canadian Medical Association Infobase, Scottish Intercollegiate Guidelines Network, Australia’s Clinical Practice Guidelines Portal, Trip Database y National Health Service Evidence. Como fuentes complementarias, se consultó UpToDate, Base de Datos BOT plus 2.0 y un tratado de Farmacología Humana. Resultados: Las recomendaciones se refieren al manejo del estreñimiento idiopático no complicado en pacientes sin síntomas de alarma e incluyen, como tratamiento de primera línea, el consumo de fibra o de agentes formadores de masa. En pacientes que no toleran los laxantes formadores de masa o responden mal a suplementos de fibra, se recomienda el uso de laxantes osmóticos. Por último, si no hay una respuesta satisfactoria, las ecomendaciones incluyen los laxantes estimulantes. En pacientes hipertensos, debe tenerse en cuenta que el hidróxido de magnesio presenta potenciales interacciones con algunos fármacos antihipertensivos. Conclusión: La indicación farmacéutica incluye, como tratamiento de primera línea, suplementos de fibra o agentes formadores de masa. En quienes no los toleran o no responden satisfactoriamente, pueden recomendarse laxantes osmóticos o estimulantes

Indicación Farmacéutica para el estreñimiento en pacientes con diabetes e hipertensión arterial.

Introducción: El estreñimiento en pacientes con hipertensión arterial o diabetes es un motivo frecuente de consulta al farmacéutico. La indicación farmacéutica no debe interferir con la medicación habitual de estos pacientes. Objetivos: Formular recomendaciones sobre indicación farmacéutica a pacientes con diabetes y/o hipertensión arterial que acuden a la oficina de farmacia solicitando tratamiento farmacológico para el estreñimiento. Material y métodos: Mediante revisión sistemática de Guías de Práctica Clínica sobre abordaje del estreñimiento, se han elaborado recomendaciones sobre indicación farmacéutica a pacientes con diabetes y/o hipertensión arterial que acuden a la oficina de farmacia solicitando tratamiento farmacológico. Tras diseñar una estrategia de búsqueda, se seleccionaron las fuentes bibliográficas y se llevó a cabo la recogida de información. La búsqueda bibliográfica se realizó en los siguientes recursos web: Medline, GuíaSalud, National Guideline Clearinghouse, Canadian Medical Association Infobase, Scottish Intercollegiate Guidelines Network, Australia’s Clinical Practice Guidelines Portal, Trip Database y National Health Service Evidence. Como fuentes complementarias, se consultó UpToDate, Base de Datos BOT plus 2.0 y un tratado de Farmacología Humana. Resultados: Las recomendaciones se refieren al manejo del estreñimiento idiopático no complicado en pacientes sin síntomas de alarma e incluyen, como tratamiento de primera línea, el consumo de fibra o de agentes formadores de masa. En pacientes que no toleran los laxantes formadores de masa o responden mal a suplementos de fibra, se recomienda el uso de laxantes osmóticos. Por último, si no hay una respuesta satisfactoria, las ecomendaciones incluyen los laxantes estimulantes. En pacientes hipertensos, debe tenerse en cuenta que el hidróxido de magnesio presenta potenciales interacciones con algunos fármacos antihipertensivos. Conclusión: La indicación farmacéutica incluye, como tratamiento de primera línea, suplementos de fibra o agentes formadores de masa. En quienes no los toleran o no responden satisfactoriamente, pueden recomendarse laxantes osmóticos o estimulantes

High throughput estimation of functional cell activities reveals disease mechanisms and predicts relevant clinical outcomes

This work is supported by grants BIO2014- 57291-R from the Spanish Ministry of Economy and Competitiveness and “Plataforma de Recursos Biomoleculares y Bioinformáticos” PT13/0001/0007 from the ISCIII, both co-funded with European Regional Development Funds (ERDF); PROMETEOII/2014/025 from the Generalitat Valenciana (GVA-FEDER); Fundació la Marató TV3 (ref. 20133134); and EU H2020- INFRADEV-1-2015-1 ELIXIR-EXCELERATE (ref. 676559) and EU FP7-People ITN Marie Curie Project (ref 316861)

Fcγ Receptors in Solid Organ Transplantation.

In the current era, one of the major factors limiting graft survival is chronic antibody-mediated rejection (ABMR), whilst patient survival is impacted by the effects of immunosuppression on susceptibility to infection, malignancy and atherosclerosis. IgG antibodies play a role in all of these processes, and many of their cellular effects are mediated by Fc gamma receptors (FcγRs). These surface receptors are expressed by most immune cells, including B cells, natural killer cells, dendritic cells and macrophages. Genetic variation in FCGR genes is likely to affect susceptibility to ABMR and to modulate the physiological functions of IgG. In this review, we discuss the potential role played by FcγRs in determining outcomes in solid organ transplantation, and how genetic polymorphisms in these receptors may contribute to variations in transplant outcome.MRC is supported by the NIHR Cambridge BRC, the NIHR Blood and Transplant Research Unit (Cambridge) and by a Medical Research Council New Investigator Grant (MR/N024907/1).This is the final version of the article. It first appeared from Springer via https://doi.org/10.1007/s40472-016-0116-

Epigenetics, heritability and longitudinal analysis

© 2018 The Author(s). Background: Longitudinal data and repeated measurements in epigenome-wide association studies (EWAS) provide a rich resource for understanding epigenetics. We summarize 7 analytical approaches to the GAW20 data sets that addressed challenges and potential applications of phenotypic and epigenetic data. All contributions used the GAW20 real data set and employed either linear mixed effect (LME) models or marginal models through generalized estimating equations (GEE). These contributions were subdivided into 3 categories: (a) quality control (QC) methods for DNA methylation data; (b) heritability estimates pretreatment and posttreatment with fenofibrate; and (c) impact of drug response pretreatment and posttreatment with fenofibrate on DNA methylation and blood lipids. Results: Two contributions addressed QC and identified large statistical differences with pretreatment and posttreatment DNA methylation, possibly a result of batch effects. Two contributions compared epigenome-wide heritability estimates pretreatment and posttreatment, with one employing a Bayesian LME and the other using a variance-component LME. Density curves comparing these studies indicated these heritability estimates were similar. Another contribution used a variance-component LME to depict the proportion of heritability resulting from a genetic and shared environment. By including environmental exposures as random effects, the authors found heritability estimates became more stable but not significantly different. Two contributions investigated treatment response. One estimated drug-associated methylation effects on triglyceride levels as the response, and identified 11 significant cytosine-phosphate-guanine (CpG) sites with or without adjusting for high-density lipoprotein. The second contribution performed weighted gene coexpression network analysis and identified 6 significant modules of at least 30 CpG sites, including 3 modules with topological differences pretreatment and posttreatment. Conclusions: Four conclusions from this GAW20 working group are: (a) QC measures are an important consideration for EWAS studies that are investigating multiple time points or repeated measurements; (b) application of heritability estimates between time points for individual CpG sites is a useful QC measure for DNA methylation studies; (c) drug intervention demonstrated strong epigenome-wide DNA methylation patterns across the 2 time points; and (d) new statistical methods are required to account for the environmental contributions of DNA methylation across time. These contributions demonstrate numerous opportunities exist for the analysis of longitudinal data in future epigenetic studies

Molecular Characterization of Clinical Isolates of Aeromonas Species from Malaysia

Background: Aeromonas species are common inhabitants of aquatic environments giving rise to infections in both fish and humans. Identification of aeromonads to the species level is problematic and complex due to their phenotypic and genotypic heterogeneity. Methodology/Principal Findings: Aeromonas hydrophila or Aeromonas sp were genetically re-identified using a combination of previously published methods targeting GCAT, 16S rDNA and rpoD genes. Characterization based on the genus specific GCAT-PCR showed that 94 (96%) of the 98 strains belonged to the genus Aeromonas. Considering the patterns obtained for the 94 isolates with the 16S rDNA-RFLP identification method, 3 clusters were recognised, i.e. A. caviae (61%), A. hydrophila (17%) and an unknown group (22%) with atypical RFLP restriction patterns. However, the phylogenetic tree constructed with the obtained rpoD sequences showed that 47 strains (50%) clustered with the sequence of the type strain of A. aquariorum, 18 (19%) with A. caviae, 16 (17%) with A. hydrophila, 12 (13%) with A. veronii and one strain (1%) with the type strain of A. trota. PCR investigation revealed the presence of 10 virulence genes in the 94 isolates as: lip (91%), exu (87%), ela (86%), alt (79%), ser (77%), fla (74%), aer (72%), act (43%), aexT (24%) and ast (23%). Conclusions/Significance: This study emphasizes the importance of using more than one method for the correct identification of Aeromonas strains. The sequences of the rpoD gene enabled the unambiguous identication of the 9