The Cure: Making a game of gene selection for breast cancer survival prediction

Motivation: Molecular signatures for predicting breast cancer prognosis could greatly improve care through personalization of treatment. Computational analyses of genome-wide expression datasets have identified such signatures, but these signatures leave much to be desired in terms of accuracy, reproducibility and biological interpretability. Methods that take advantage of structured prior knowledge (e.g. protein interaction networks) show promise in helping to define better signatures but most knowledge remains unstructured. Crowdsourcing via scientific discovery games is an emerging methodology that has the potential to tap into human intelligence at scales and in modes previously unheard of. Here, we developed and evaluated a game called The Cure on the task of gene selection for breast cancer survival prediction. Our central hypothesis was that knowledge linking expression patterns of specific genes to breast cancer outcomes could be captured from game players. We envisioned capturing knowledge both from the players prior experience and from their ability to interpret text related to candidate genes presented to them in the context of the game. Results: Between its launch in Sept. 2012 and Sept. 2013, The Cure attracted more than 1,000 registered players who collectively played nearly 10,000 games. Gene sets assembled through aggregation of the collected data clearly demonstrated the accumulation of relevant expert knowledge. In terms of predictive accuracy, these gene sets provided comparable performance to gene sets generated using other methods including those used in commercial tests. The Cure is available at http://genegames.org/cure

Quantitating the epigenetic transformation contributing to cholesterol homeostasis using Gaussian process.

To understand the impact of epigenetics on human misfolding disease, we apply Gaussian-process regression (GPR) based machine learning (ML) (GPR-ML) through variation spatial profiling (VSP). VSP generates population-based matrices describing the spatial covariance (SCV) relationships that link genetic diversity to fitness of the individual in response to histone deacetylases inhibitors (HDACi). Niemann-Pick C1 (NPC1) is a Mendelian disorder caused by >300 variants in the NPC1 gene that disrupt cholesterol homeostasis leading to the rapid onset and progression of neurodegenerative disease. We determine the sequence-to-function-to-structure relationships of the NPC1 polypeptide fold required for membrane trafficking and generation of a tunnel that mediates cholesterol flux in late endosomal/lysosomal (LE/Ly) compartments. HDACi treatment reveals unanticipated epigenomic plasticity in SCV relationships that restore NPC1 functionality. GPR-ML based matrices capture the epigenetic processes impacting information flow through central dogma, providing a framework for quantifying the effect of the environment on the healthspan of the individual

Linking genes to diseases with a SNPedia-Gene Wiki mashup

<p>Abstract</p> <p>Background</p> <p>A variety of topic-focused wikis are used in the biomedical sciences to enable the mass-collaborative synthesis and distribution of diverse bodies of knowledge. To address complex problems such as defining the relationships between genes and disease, it is important to bring the knowledge from many different domains together. Here we show how advances in wiki technology and natural language processing can be used to automatically assemble ‘meta-wikis’ that present integrated views over the data collaboratively created in multiple source wikis.</p> <p>Results</p> <p>We produced a semantic meta-wiki called the Gene Wiki+ that automatically mirrors and integrates data from the Gene Wiki and SNPedia. The Gene Wiki+, available at (<url>http://genewikiplus.org/</url>), captures 8,047 distinct gene-disease relationships. SNPedia accounts for 4,149 of the gene-disease pairs, the Gene Wiki provides 4,377 and only 479 appear independently in both sources. All of this content is available to query and browse and is provided as linked open data.</p> <p>Conclusions</p> <p>Wikis contain increasing amounts of diverse, biological information useful for elucidating the connections between genes and disease. The Gene Wiki+ shows how wiki technology can be used in concert with natural language processing to provide integrated views over diverse underlying data sources.</p

Insecticidal activity of culture supernatants from Bacillus thuringiensis Berliner strains against Spodoptera frugiperda Smith (Lepidoptera: Noctuidae) larvae.

Recentemente, proteinas inseticidas vegetativas (Vips), identificadas no sobrenadante da cultura de certas cepas de Bacillus thuringiensis (B.t.), foram capazes de controlar alguns insetos-praga economicamente importantes. Como avaliacao do potencial de aplicabilidade destas proteinas contra a lagarta-do-cartucho (Spodoptera frugiperda Smith), o inseto-praga mais importante da cultura do milho, as caracteristicas e o efeito de mortalidade do sobrenadante da cultura de cinco cepas de B.t. foram investigadas. Notaveis diferencas entre as cepas foram detectadas, nao somente em termos de eficiencia na mortalidade dos insetos, mas tambem nas diferencas de mortalidade entre os sobrenadantes aquecido e nao-aquecido tratamentos estes que foram usados para distinguir a fracao proteica inseticida termo-sensivel de outra fracao termo-estavel, de natureza nao-proteica (b-exotoxinas). Os padroes qualitativo , quantitativo e temporal de secrecao da proteina total no meio (sobrenadante) foram avaliados por espectrofotometria e eletroforese em gel de poliacrilamida. As cepas apresentaram distintas taxas de crescimento e tempos de secrecao de proteinas em relacao a densidade de celulas na cultura. Alem disso, o padrao de bandas eletroforeticas tambem variou de maneira cepa-especifica, em ambas condicoes desnaturantes e nao-desnaturantes. Polipeptideos que apresentaram peso molecular semelhantes aos esperados para proteinas Vip3A identificadas anteriormente foram encontradas em cepas com alta taxa de mortalidade do sobrenadante. Os dados sugerem a possibilidade e a utilidade de pesquisar fracoes inseticidas de natureza proteica (do tipo Vip) em sobrenadantes de B.t., como forma para desenvolver alternativas especificas e eficientes de controle biologico que possam ser empregadas em programas de manejo integrado de S. frugiperda em milho tropical

A Preliminary Analysis of Anthropogenic and Natural Impacts on a Volcanic Lake Ecosystem in Southern Italy by UAV-Based Monitoring

Lakes play an important role in providing various ecosystem services. However, stressors such as climate change, land use, or land-cover change threaten the ecological functions of lakes. National and international legislations address these threats and establish consistent, long-term monitoring schemes. Remote sensing techniques based on the use of Unmanned Aerial Vehicles (UAV) have recently been demonstrated to provide accurate and low-cost spatio-temporal views for the assessment of the ecological status of aquatic ecosystems and the identification of areas at risk of contamination. Few studies have been carried out so far on the employment of these tools in the monitoring of lakes. Therefore, high-resolution UAV surveys were used to analyse and evaluate natural and anthropogenic impacts on the habitat status of a volcanic lake in a protected area. Five UAV flights took place during a year-long cycle (November 2020 to November 2021) in a volcanic lake located in southern Italy. For each flight performance, an orthomosaic of georeferenced RGB images was obtained, and the different features of interest were monitored and quantified using automated processing in a GIS environment. The UAV images made it possible not only to estimate the flooded shores but also to detect the impact of human-made structures and infrastructures on the lagoon environment. It has been possible to observe how the rapid changes in lake-water level have led to the submersion of about 90.000 m(2) of terrain in winter, causing the fragmentation and degradation of habitats, while the connectivity of the natural ecosystem has been threatened by the presence of the road around the lake. The proposed methodology is rather simple and easily replicable by decision makers and local administrators and can be useful for choosing the best restoration interventions

Efeito de isolados de Baculovirus em lagartas de Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae) e sua caracterização utilizando PCR.

xEdição dos resumos do Congresso Nacional de Genética, Gramado, 1999