GeneMANIA update 2018.

GeneMANIA (http://genemania.org) is a flexible user-friendly web site for generating hypotheses about gene function, analyzing gene lists and prioritizing genes for functional assays. Given a query gene list, GeneMANIA finds functionally similar genes using a wealth of genomics and proteomics data. In this mode, it weights each functional genomic dataset according to its predictive value for the query. Another use of GeneMANIA is gene function prediction. Given a single query gene, GeneMANIA finds genes likely to share function with it based on their interactions with it. Enriched Gene Ontology categories among this set can point to the function of the gene. Nine organisms are currently supported (Arabidopsis thaliana, Caenorhabditis elegans, Danio rerio, Drosophila melanogaster, Escherichia coli, Homo sapiens, Mus musculus, Rattus norvegicus and Saccharomyces cerevisiae). Hundreds of data sets and hundreds of millions of interactions have been collected from GEO, BioGRID, IRefIndex and I2D, as well as organism-specific functional genomics data sets. Users can customize their search by selecting specific data sets to query and by uploading their own data sets to analyze. We have recently updated the user interface to GeneMANIA to make it more intuitive and make more efficient use of visual space. GeneMANIA can now be used effectively on a variety of devices.

Neuro-ophthalmological findings in TAFRO syndrome in a patient from South America, a variant of multicentric Castleman's disease.

BACKGROUND: To report the neuro-ophthalmological findings in the TAFRO syndrome in a South American patient. METHODS: This is a case report of a patient with TAFRO syndrome. RESULTS: We present the case of a 66-year-old woman with TAFRO syndrome and multicentric Castleman disease, who developed ophthalmic manifestations, as a rare complication, including optic disk edema and serous retinal detachment, which improved with conventional therapy. CONCLUSIONS: The optic disk edema could be present as a neuro-ophthalmological finding in TAFRO syndrome. To the best of our knowledge, this is the first report on the ophthalmic manifestations in the TAFRO syndrome.

Novel cardiovascular gene functions revealed via systematic phenotype prediction in zebrafish.

Comprehensive functional annotation of vertebrate genomes is fundamental to biological discovery. Reverse genetic screening has been highly useful for determination of gene function, but is untenable as a systematic approach in vertebrate model organisms given the number of surveyable genes and observable phenotypes. Unbiased prediction of gene-phenotype relationships offers a strategy to direct finite experimental resources towards likely phenotypes, thus maximizing de novo discovery of gene functions. Here we prioritized genes for phenotypic assay in zebrafish through machine learning, predicting the effect of loss of function of each of 15,106 zebrafish genes on 338 distinct embryonic anatomical processes. Focusing on cardiovascular phenotypes, the learning procedure predicted known knockdown and mutant phenotypes with high precision. In proof-of-concept studies we validated 16 high-confidence cardiac predictions using targeted morpholino knockdown and initial blinded phenotyping in embryonic zebrafish, confirming a significant enrichment for cardiac phenotypes as compared with morpholino controls. Subsequent detailed analyses of cardiac function confirmed these results, identifying novel physiological defects for 11 tested genes. Among these we identified tmem88a, a recently described attenuator of Wnt signaling, as a discrete regulator of the patterning of intercellular coupling in the zebrafish cardiac epithelium. Thus, we show that systematic prioritization in zebrafish can accelerate the pace of developmental gene function discovery.

Novel function discovery with GeneMANIA: a new integrated resource for gene function prediction in Escherichia coli.

MOTIVATION: The model bacterium Escherichia coli is among the best studied prokaryotes, yet nearly half of its proteins are still of unknown biological function. This is despite a wealth of available large-scale physical and genetic interaction data. To address this, we extended the GeneMANIA function prediction web application developed for model eukaryotes to support E.coli. RESULTS: We integrated 48 distinct E.coli functional interaction datasets and used the GeneMANIA algorithm to produce thousands of novel functional predictions and prioritize genes for further functional assays. Our analysis achieved cross-validation performance comparable to that reported for eukaryotic model organisms, and revealed new functions for previously uncharacterized genes in specific bioprocesses, including components required for cell adhesion, iron-sulphur complex assembly and ribosome biogenesis. The GeneMANIA approach for network-based function prediction provides an innovative new tool for probing mechanisms underlying bacterial bioprocesses. CONTACT: gary.bader@utoronto.ca; mohan.babu@uregina.ca SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

GeneMANIA prediction server 2013 update.

GeneMANIA (http://www.genemania.org) is a flexible user-friendly web interface for generating hypotheses about gene function, analyzing gene lists and prioritizing genes for functional assays. Given a query gene list, GeneMANIA extends the list with functionally similar genes that it identifies using available genomics and proteomics data. GeneMANIA also reports weights that indicate the predictive value of each selected data set for the query. GeneMANIA can also be used in a function prediction setting: given a query gene, GeneMANIA finds a small set of genes that are most likely to share function with that gene based on their interactions with it. Enriched Gene Ontology categories among this set can sometimes point to the function of the gene. Seven organisms are currently supported (Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, Mus musculus, Homo sapiens, Rattus norvegicus and Saccharomyces cerevisiae), and hundreds of data sets have been collected from GEO, BioGRID, IRefIndex and I2D, as well as organism-specific functional genomics data sets. Users can customize their search by selecting specific data sets to query and by uploading their own data sets to analyze.

Evaluation of Facebook and Twitter Monitoring to Detect Safety Signals for Medical Products: An Analysis of Recent FDA Safety Alerts.

INTRODUCTION: The rapid expansion of the Internet and computing power in recent years has opened up the possibility of using social media for pharmacovigilance. While this general concept has been proposed by many, central questions remain as to whether social media can provide earlier warnings for rare and serious events than traditional signal detection from spontaneous report data. OBJECTIVE: Our objective was to examine whether specific product-adverse event pairs were reported via social media before being reported to the US FDA Adverse Event Reporting System (FAERS). METHODS: A retrospective analysis of public Facebook and Twitter data was conducted for 10 recent FDA postmarketing safety signals at the drug-event pair level with six negative controls. Social media data corresponding to two years prior to signal detection of each product-event pair were compiled. Automated classifiers were used to identify each 'post with resemblance to an adverse event' (Proto-AE), among English language posts. A custom dictionary was used to translate Internet vernacular into Medical Dictionary for Regulatory Activities (MedDRA®) Preferred Terms. Drug safety physicians conducted a manual review to determine causality using World Health Organization-Uppsala Monitoring Centre (WHO-UMC) assessment criteria. Cases were also compared with those reported in FAERS. FINDINGS: A total of 935,246 posts were harvested from Facebook and Twitter, from March 2009 through October 2014. The automated classifier identified 98,252 Proto-AEs. Of these, 13 posts were selected for causality assessment of product-event pairs. Clinical assessment revealed that posts had sufficient information to warrant further investigation for two possible product-event associations: dronedarone-vasculitis and Banana Boat Sunscreen--skin burns. No product-event associations were found among the negative controls. In one of the positive cases, the first report occurred in social media prior to signal detection from FAERS, whereas the other case occurred first in FAERS. CONCLUSIONS: An efficient semi-automated approach to social media monitoring may provide earlier insights into certain adverse events. More work is needed to elaborate additional uses for social media data in pharmacovigilance and to determine how they can be applied by regulatory agencies.

Sperm processing for advanced reproductive technologies: Where are we today?

Assisted reproductive technologies (ARTs) utilize sperm sorting methods to select viable sperm from the semen samples. Conventional sperm sorting techniques in current use are density gradient centrifugation, direct swim-up, and conventional swim-up. These methods use multiple centrifugation steps, which have been shown to generate reactive oxygen species (ROS) that decrease DNA integrity and damage sperm. Newer technologies, such as microfluidics, electrophoresis, motile sperm organelle morphology examination (MSOME), and birefringence eliminate the centrifugation steps and can improve the selection of sperm with higher DNA integrity, normal morphology, and motility as well as improved artificial insemination outcomes. In this review, we discuss some recent research in centrifugation and non-centrifugation based techniques and their effect on sperm quality and ART outcomes.

Social Media Listening for Routine Post-Marketing Safety Surveillance.

INTRODUCTION: Post-marketing safety surveillance primarily relies on data from spontaneous adverse event reports, medical literature, and observational databases. Limitations of these data sources include potential under-reporting, lack of geographic diversity, and time lag between event occurrence and discovery. There is growing interest in exploring the use of social media ('social listening') to supplement established approaches for pharmacovigilance. Although social listening is commonly used for commercial purposes, there are only anecdotal reports of its use in pharmacovigilance. Health information posted online by patients is often publicly available, representing an untapped source of post-marketing safety data that could supplement data from existing sources. OBJECTIVES: The objective of this paper is to describe one methodology that could help unlock the potential of social media for safety surveillance. METHODS: A third-party vendor acquired 24 months of publicly available Facebook and Twitter data, then processed the data by standardizing drug names and vernacular symptoms, removing duplicates and noise, masking personally identifiable information, and adding supplemental data to facilitate the review process. The resulting dataset was analyzed for safety and benefit information. RESULTS: In Twitter, a total of 6,441,679 Medical Dictionary for Regulatory Activities (MedDRA(®)) Preferred Terms (PTs) representing 702 individual PTs were discussed in the same post as a drug compared with 15,650,108 total PTs representing 946 individual PTs in Facebook. Further analysis revealed that 26 % of posts also contained benefit information. CONCLUSION: Social media listening is an important tool to augment post-marketing safety surveillance. Much work remains to determine best practices for using this rapidly evolving data source.

Increasing Patient Engagement in Pharmacovigilance Through Online Community Outreach and Mobile Reporting Applications: An Analysis of Adverse Event Reporting for the Essure Device in the US.

BACKGROUND: Preparing and submitting a voluntary adverse event (AE) report to the US Food and Drug Administration (FDA) for a medical device typically takes 40 min. User-friendly Web and mobile reporting apps may increase efficiency. Further, coupled with strategies for direct patient involvement, patient engagement in AE reporting may be improved. In 2012, the FDA Center for Devices and Radiologic Health (CDRH) launched a free, public mobile AE reporting app, MedWatcher, for patients and clinicians. During the same year, a patient community on Facebook adopted the app to submit reports involving a hysteroscopic sterilization device, brand name Essure®. METHODS: Patient community outreach was conducted to administrators of the group "Essure Problems" (approximately 18,000 members as of June 2015) to gather individual case safety reports (ICSRs). After agreeing on key reporting principles, group administrators encouraged members to report via the app. Semi-structured forms in the app mirrored fields of the MedWatch 3500 form. ICSRs were transmitted to CDRH via an electronic gateway, and anonymized versions were posted in the app. Data collected from May 11, 2013 to December 7, 2014 were analyzed. Narrative texts were coded by trained and certified MedDRA coders (version 17). Descriptive statistics and metrics, including VigiGrade completeness scores, were analyzed. Various incentives and motivations to report in the Facebook group were observed. RESULTS: The average Essure AE report took 11.4 min (±10) to complete. Submissions from 1349 women, average age 34 years, were analyzed. Serious events, including hospitalization, disability, and permanent damage after implantation, were reported by 1047 women (77.6 %). A total of 13,135 product-event pairs were reported, comprising 327 unique preferred terms, most frequently fatigue (n = 491), back pain (468), and pelvic pain (459). Important medical events (IMEs), most frequently mental impairment (142), device dislocation (108), and salpingectomy (62), were reported by 598 women (44.3 %). Other events of interest included loss of libido (n = 115); allergy to metals (109), primarily nickel; and alopecia (252). VigiGrade completeness scores were high, averaging 0.80 (±0.15). Reports received via the mobile app were considered "well documented" 55.9 % of the time, compared with an international average of 13 % for all medical products. On average, there were 15 times more reports submitted per month via the app with patient community support versus traditional pharmacovigilance portals. CONCLUSIONS: Outreach via an online patient community, coupled with an easy-to-use app, allowed for rapid and detailed ICSRs to be submitted, with gains in efficiency. Two-way communication and public posting of narratives led to successful engagement within a Motivation-Incentive-Activation-Behavior framework, a conceptual model for successful crowdsourcing. Reports submitted by patients were considerably more complete than those submitted by physicians in routine spontaneous reports. Further research is needed to understand how biases operate differently from those of traditional pharmacovigilance.

GeneMANIA: Fast gene network construction and function prediction for Cytoscape.

The GeneMANIA Cytoscape app enables users to construct a composite gene-gene functional interaction network from a gene list. The resulting network includes the genes most related to the original list, and functional annotations from Gene Ontology. The edges are annotated with details about the publication or data source the interactions were derived from. The app leverages GeneMANIA's database of 1800+ networks, containing over 500 million interactions spanning 8 organisms: A. thaliana, C. elegans, D. melanogaster, D. rerio, H. sapiens, M. musculus, R. norvegicus, and S. cerevisiae. Users may also import their own organisms, networks, and expression profiles. The app is compatible with Cytoscape versions 2 and 3.

Tamizaje fitoquímico y actividad antibacteriana de los extractos secos de tinturas al 20 por ciento de Mammea americana L / Phytochemical screening and antibacterial activity of dry extracts of 20 por ciento tinctures from Mammea americana L

Introducción: el mamey amarillo (Mammea americana L.) se utiliza ampliamente en la curación de diversos tipos de enfermedades producidas por parásitos e insectos. Objetivo: realizar el tamizaje fitoquímico y determinar la actividad antibacteriana de los extractos secos de la tintura al 20 por ciento de las hojas y corteza del fuste de esta planta. Métodos: se recolectaron hojas y corteza del fuste de la planta objeto de estudio, que fueron lavadas, desinfectadas, secadas y pulverizadas. Luego se procedió a la elaboración de las tinturas al 20 por ciento por el método de maceración de la droga. Los extractos secos de las partes estudiadas de la planta se obtuvieron a partir de las tinturas al 20 por ciento y se emplearon para los ensayos del tamizaje fitoquímico y la evaluación de la actividad antibacteriana. Resultados: se comprobó la existencia de una alta diversidad de metabolitos secundarios, con predominio de los alcaloides, coumarinas, fenoles o taninos, quinonas y flavonoides. Los extractos secos mostraron actividad antibacteriana in vitro frente a la cepa de Staphylococcus aureus (ATCC 29737). Conclusiones: se destacan, por su significativa presencia, flavonoides, alcaloides, taninos y cumarinas, los cuales resultan de interés biológico y farmacológico por sus posibles aplicaciones terapéuticas

Introduction: the yellow mammee (Mammea americana L.) is widely used to cure different diseases caused by parasites and insects. Objective: to perform a phytochemical screening and to determine antibacterial activity of dry extracts of 20 percent tincture from the leaves and the bark of this plant. Methods: the leaves and stem bark of the plant were harvested, washed, disinfected, dried and crushed. Then it proceeded to the preparation of 20 percent tinctures through drug maceration. The dried extracts of the studied parts were obtained from the 20 percent tinctures and used to evaluate the phytochemical screening tests and the antibacterial activity. Results: the existence of a high diversity of secondary metabolites, predominantly alkaloids, coumarins, phenols and / or tannins, quinones, and flavonoids were confirmed. The dried extracts showed antibacterial activity in vitro against Staphylococcus aureus (ATCC 29737). Conclusions: flavonoids, alkaloids, tannins and coumarins, which are of biological and pharmacological interest for their potential therapeutic applications, were significantly present in these extracts

Consumo de videjjuegos y juegos para computador influencias sobre la atención,, memoria, rendimiento académico y problemas de condutaa / Use of vieogamess and comuter games: influences on attention, memory, accademic achievement and problems behavoor

El presente estudio se diseñó con el propósito de identificar la relación existente entre el consumo de videojuegos y juegos por ordenador, con la memoria, la atención, el rendimiento académico y problemas de conducta en niños escolarizados de Bogotá. La memoria y la atención se evaluaron mediante un conjunto de diferentes escalas de la Batería ENI (Matute, Rosselli, Ardila, & Ostrosky-Solís, 2007), el rendimiento académico con boletines escolares y los problemas de conducta a través del cuestionario CBCL / 6-18 (Child Behavior Checklist) de (Achenbach y Edelbrock, 1983). Participaron 123 niños y 99 padres de familia en 2 estudios experimentales con diseño factorial. Con los resultados no fue posible confirmar las hipótesis respecto a un cambio significativo en las pruebas de memoria, atención visual selectiva y atención auditiva a nivel intrasujeto, sin embargo a partir de estas variables se identificaron diferencias estadísticamente significativas entre los niños(as) por influencia del factor consumo habitual a videojuegos. No se encontraron diferencias entre el nivel de consumo habitual de los niños(as) y las variables de rendimiento académico y la lista de problemas de conducta.

This study was designed to identify the relationship between video and computer games use on attention, memory, academic performance and problems behavior in school children in Bogotá. Memory and attention were assessed using a set of different scales of ENI Battery (Matute, Rosselli, Ardila, & Os-trosky-Solís, 2007). For Academic performance, school newsletters were used. Behavioral problems were assessed through the CBCL / 6 -18 questionnaire (Child Behavior Checklist) of (Achenbach & Edelbrock, 1983). 123 children and 99 parents were enrolled in 2 factorial design experimental studies. The results did not support the hypothesis of a significant change in memory tests, or intra-subject selective visual and hearing attention. However, these variables showed significant differences among children exposed to habitual videogames consumption. No differences were found between the level of regular video games consumption in school children and academic performance variables or behavioral problems.