GeneBrowser 2: an application to explore and identify common biological traits in a set of genes

<p>Abstract</p> <p>Background</p> <p>The development of high-throughput laboratory techniques created a demand for computer-assisted result analysis tools. Many of these techniques return lists of genes whose interpretation requires finding relevant biological roles for the problem at hand. The required information is typically available in public databases, and usually, this information must be manually retrieved to complement the analysis. This process is a very time-consuming task that should be automated as much as possible.</p> <p>Results</p> <p>GeneBrowser is a web-based tool that, for a given list of genes, combines data from several public databases with visualisation and analysis methods to help identify the most relevant and common biological characteristics. The functionalities provided include the following: a central point with the most relevant biological information for each inserted gene; a list of the most related papers in PubMed and gene expression studies in ArrayExpress; and an extended approach to functional analysis applied to Gene Ontology, homologies, gene chromosomal localisation and pathways.</p> <p>Conclusions</p> <p>GeneBrowser provides a unique entry point to several visualisation and analysis methods, providing fast and easy analysis of a set of genes. GeneBrowser fills the gap between Web portals that analyse one gene at a time and functional analysis tools that are limited in scope and usually desktop-based.</p

Genome-scale modeling of Chinese hamster ovary cells by hybrid semi-parametric flux balance analysis

Funding Information: This work was sponsored by GlaxoSmithKline Biologicals SA whereby the NOVA University Lisbon was engaged under an Agreement for R and D Services. All authors were involved in the conception and design of the study. PD’s lab performed the experiments/acquired the data. JR, GO, RO analyzed and interpreted the data. All authors were involved in drafting the manuscript or critically revising it for important intellectual content. All authors had full access to the data and approved the manuscript before it was submitted by the corresponding author. Publisher Copyright: © 2022, The Author(s).Flux balance analysis (FBA) is currently the standard method to compute metabolic fluxes in genome-scale networks. Several FBA extensions employing diverse objective functions and/or constraints have been published. Here we propose a hybrid semi-parametric FBA extension that combines mechanistic-level constraints (parametric) with empirical constraints (non-parametric) in the same linear program. A CHO dataset with 27 measured exchange fluxes obtained from 21 reactor experiments served to evaluate the method. The mechanistic constraints were deduced from a reduced CHO-K1 genome-scale network with 686 metabolites, 788 reactions and 210 degrees of freedom. The non-parametric constraints were obtained by principal component analysis of the flux dataset. The two types of constraints were integrated in the same linear program showing comparable computational cost to standard FBA. The hybrid FBA is shown to significantly improve the specific growth rate prediction under different constraints scenarios. A metabolically efficient cell growth feed targeting minimal byproducts accumulation was designed by hybrid FBA. It is concluded that integrating parametric and nonparametric constraints in the same linear program may be an efficient approach to reduce the solution space and to improve the predictive power of FBA methods when critical mechanistic information is missing.publishersversionpublishe

Weakly-supervised classification of HER2 expression in breast cancer haematoxylin and eosin stained slides

Human epidermal growth factor receptor 2 (HER2) evaluation commonly requires immunohistochemistry (IHC) tests on breast cancer tissue, in addition to the standard haematoxylin and eosin (H&E) staining tests. Additional costs and time spent on further testing might be avoided if HER2 overexpression could be effectively inferred from H&E stained slides, as a preliminary indication of the IHC result. In this paper, we propose the first method that aims to achieve this goal. The proposed method is based on multiple instance learning (MIL), using a convolutional neural network (CNN) that separately processes H&E stained slide tiles and outputs an IHC label. This CNN is pretrained on IHC stained slide tiles but does not use these data during inference/testing. H&E tiles are extracted from invasive tumour areas segmented with the HASHI algorithm. The individual tile labels are then combined to obtain a single label for the whole slide. The network was trained on slides from the HER2 Scoring Contest dataset (HER2SC) and tested on two disjoint subsets of slides from the HER2SC database and the TCGA-TCIA-BRCA (BRCA) collection. The proposed method attained 83.3% classification accuracy on the HER2SC test set and 53.8% on the BRCA test set. Although further efforts should be devoted to achieving improved performance, the obtained results are promising, suggesting that it is possible to perform HER2 overexpression classification on H&E stained tissue slides.publishersversionpublishe

Planning forest recreation: environmental economic instruments and the public participation

In Portugal there is a growing demand for natural areas that provide a wide range of outdoor recreation. This paper focuses on the particular case of the Mata Nacional de Leiria (Leiria National Forest). This is a pine tree forest with 11,000 hectares and eight centuries of history. It has always been a public forest with open access to everyone, a fact that contributes to different kinds of use and benefits (walking, cycling, picnics, collecting firewood, fruits and berries, and other recreation activities). The proximity to a major urban and industrial centre, on one hand, and to a very popular beach coast, on the other, makes this a resource that is widely used by both residents and visitors. In the future there is the possibility of implementing a set of actions to improve forest amenities and recreation, and later the emergence of environmental tourism activities and equipment. In this context, we want to know the economic valuation that actual users attach to these recreation improvements, but also realize their preferences and opinions regarding this project. For this purpose we designed, tested and applied a double bounded dichotomous choice contingent valuation questionnaire. The results presented in this paper focus on responses to attitudinal and follow-up questions. More than 70% of respondents have positively assessed the proposed improvements to the study area and about 40% enhanced their personal opinion on the type of interventions that they consider most appropriate. Answers focus the priority areas of intervention in the Mata Nacional de Leiria, the main concerns in its development, the type of actions that should (and should not) be implemented, respondents willingness to actively take part and, also, what the public authorities' role should be. At this stage, where Mata Nacional de Leiria is being considered in terms of future recreation and tourism offers, the results obtained provide important contributions and enhance the contingent valuation survey as a tool to support recreation planning, promoting public participation and the political decision-making process

Mitochondrial membrane lipid remodeling in pathophysiology: A new target for diet and therapeutic interventions

Mitochondria are arbiters in the fragile balance between cell life and death. These organelles present an intricate membrane system, with a peculiar lipid composition and displaying transverse as well as lateral asymmetry. Some lipids are synthesized inside mitochondria, while others have to be imported or acquired in the form of precursors. Here, we review different processes, including external interventions (e.g., diet) and a range of biological events (apoptosis, disease and aging), which may result in alterations of mitochondrial membrane lipid content. Cardiolipin, the mitochondria lipid trademark, whose biosynthetic pathway is highly regulated, will deserve special attention in this review. The modulation of mitochondrial membrane lipid composition, especially by diet, as a therapeutic strategy for the treatment of some pathologies will be also addressed.Work at the authors laboratory is supported by the Portuguese Foundation for Science and Technology and FEDER/COMPETE (research Grants PTDC-QUI-QUI-101409-2008; PTDC/QUI-BIQ/ 103001/2008 and Pest-C/SAU/LA0001/2013-2014). J.P.M. acknowledges FCT for Ph.D. Grant SFRH/BD/37626/2007

Algorithm of dynamic programming for optimization of the global matching between two contours defined by ordered points

This paper presents a new assignment algorithm with order restriction. Our optimization algorithm was developed using dynamic programming. It was implemented and tested to determine the best global matching that preserves the order of the points that define two contours to be matched. In the experimental tests done, we used the affinity matrix obtained via the method proposed by Shapiro, based on geometric modeling and modal matching. \newline The proposed algorithm revealed an optimum performance, when compared with classic assignment algorithms: Hungarian Method, Simplex for Flow Problems and LAPm. Indeed, the quality of the matching improved when compared with these three algorithms, due to the disappearance of crossed matching, which is allowed by the conventional assignment algorithms. Moreover, the computational cost of this algorithm is much lower than the ones of other three, leading to enhanced execution times

Optimization of the global matching between two contours defined by ordered points using an algorithm based on dynamic programming

This paper presents a new assignment algorithm with order restriction, developed using the paradigm of dynamic programming. The algorithm was implemented and tested to determine the best global matching between two sets of points that represent the contours to be matched. In the experimental tests done, we used the affinity matrix obtained via the method proposed by Shapiro based on geometric modeling and modal matching.The proposed algorithm revealed an optimum performance, when compared with the classic assignment algorithms considered in this work: Hungarian method, Simplex for Flow Problems and LAPm. Indeed, the quality of the matching improved when compared with these three algorithms, because the crossed matching, allowed by the conventional assignment algorithms, disappeared. Besides, the computational cost of our algorithm is very low in comparison with the other three, resulting in lesser execution times