Cell nuclei segmentation in histopathological images is essential for diagnosing oral epithelial dysplasia, a condition associated with an increased risk of oral cancer. Deep learning models have demonstrated significant potential in this task, but challenges persist due to variations in staining, tissue morphology, and artifacts. This study investigates segmentation models and proposes ensemble approaches to improve instance segmentation in OED histological images. The ensemble integrates diverse segmentation models using different voting rules, with the$D_{C^{-}}$weighted averaging achieving the best results. The proposed method obtained an accuracy of$\mathbf{9 4. 0 9 \%}$and a Dice coefficient of 0.9461, surpassing individual models and demonstrating significant improvement. Comparative analysis with the literature shows that the ensemble achieved competitive performance across multiple datasets. These results reinforce the potential of ensemble learning to enhance segmentation accuracy, contributing to the development of robust computer-aided diagnosis systems.

Cancer remains a major global health threat due to its high mortality rate and the challenges associated with its treatment, especially in the later stages. It is very important that the patient identify the cancer as soon as possible to increase recovery chances, and for this, histological images are often used. These images are often looked at by a professional, who analyzes it and categorizes the tissue in labels, but it is often a difficult process for these professionals to analyze a great number of images, and that is why it is used computer vision and neural networks to aid in the identification steps of the disease. A very important network structure that can be used in computer vision is a model called U-Net, named after the U shape made by the decoding and encoding blocks, this network model extracts information while changing the size of the image, being able to get the finest to the more general features of the image. This network can also use an attention system to further improve the feature extraction phase and aid in even better segmentation, with multiple attention models for different purposes. Therefore, this study shows how these attention channels can be tweaked to improve the model results, allowing different types of attention to improve in areas of weakness of the model.

Early diagnosis of potentially malignant disorders, such as oral epithelial dysplasia (OED), is the most reliable way to prevent oral cancer. Computational algorithms have been used as a tool to aid specialists in this process. In recent years, CNN-based methods have gained more attention due to their improved results in nuclei segmentation tasks. Despite these relevant results, achieving high segmentation accuracy remains a challenging task. In this paper, we propose an ensemble of segmentation models to improve the performance of nuclei segmentation in OED histopathology images. The proposed ensemble consists of four CNN segmentation models, which were combined using three ensemble strategies: simple averaging, weighted averaging and majority voting, achieved accuracy of 90.69%, 90.70% and 88.49%, respectively, when applied to OED images. The model's performance was also evaluated on three publicly available datasets and achieved comparable performance to state-of-the-art segmentation methods. These values indicate that the proposed ensemble methods can be used in medical image analysis applications.

Liver cancer is one of the most common types of cancer according to World Health Statistics. Computer-aided diagnosis (CAD) systems are used in medical imaging for liver tumor identification and classification. Texture is a type of feature that can provide measurements of properties such as smoothness and regularity of the image. Handcraft techniques based on fractal geometry allow quantifying self-similarity properties present in images. However, new studies have shown that using information obtained from deep-learned feature maps can maximize the results of classical classifiers. This work presents an approach that investigates descriptors obtained by handcrafted and deep learning features, feature selection methods and the Hermite polynomial (HP) algorithm to classifier liver histological images. The results were evaluated using metrics such as accuracy (ACC) and the imbalance accuracy metric (IAM). The association with fractal features, Lasso regularization and the HP algorithm achieved 0.98 of IAM and 99.53% ACC, which was relevant when evaluated with other studies in the literature.

SUMMARY: Machine learning algorithms for link prediction can be valuable tools for hypothesis generation. However, many current algorithms are black boxes or lack good user interfaces that could facilitate insight into why predictions are made. We present LinkExplorer, a software suite for predicting, explaining and exploring links in large biomedical knowledge graphs. LinkExplorer integrates our novel, rule-based link prediction engine SAFRAN, which was recently shown to outcompete other explainable algorithms and established black-box algorithms. Here, we demonstrate highly competitive evaluation results of our algorithm on multiple large biomedical knowledge graphs, and release a web interface that allows for interactive and intuitive exploration of predicted links and their explanations. AVAILABILITY AND IMPLEMENTATION: A publicly hosted instance, source code and further documentation can be found at https://github.com/OpenBioLink/Explorer. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Oral epithelial dysplasia is a common type of pre-cancerous lesion that can be categorized as mild, moderate and severe. The manual diagnosis of this type of lesion is a time consuming and complex task. The use of digital systems applied to microscopic image analysis can aid the decision making of specialists. In recent years, deep learning-based methods are getting more attention due to its improved results in nuclei segmentation tasks. In this paper, we propose a methodology for nuclei segmentation on images of dysplastic tissues using neural networks. Several optimization algorithms and color normalization methods were evaluated. The methodology was performed on a dataset of mice tongue images. The experimental evaluations showed that the Nadam optimizer in combination with images without the use of color normalization obtained the best results. The method was able to segment the images with an average accuracy of 0.887, the sensitivity of 0.762 and specificity of 0.942. The algorithm was compared to other segmentation methods and showed relevant results. These values indicate that the proposed method can be used as a tool to aid specialists in the nuclei analysis of histological images of the buccal cavity.

BACKGROUND: The amount of published full-text articles has increased dramatically. Text mining tools configure an essential approach to building biological networks, updating databases and providing annotation for new pathways. PESCADOR is an online web server based on LAITOR and NLProt text mining tools, which retrieves protein-protein co-occurrences in a tabular-based format, adding a network schema. Here we present an HPC-oriented version of PESCADOR's native text mining tool, renamed to LAITOR4HPC, aiming to access an unlimited abstract amount in a short time to enrich available networks, build new ones and possibly highlight whether fields of research have been exhaustively studied. RESULTS: By taking advantage of parallel computing HPC infrastructure, the full collection of MEDLINE abstracts available until June 2017 was analyzed in a shorter period (6 days) when compared to the original online implementation (with an estimated 2 years to run the same data). Additionally, three case studies were presented to illustrate LAITOR4HPC usage possibilities. The first case study targeted soybean and was used to retrieve an overview of published co-occurrences in a single organism, retrieving 15,788 proteins in 7894 co-occurrences. In the second case study, a target gene family was searched in many organisms, by analyzing 15 species under biotic stress. Most co-occurrences regarded Arabidopsis thaliana and Zea mays. The third case study concerned the construction and enrichment of an available pathway. Choosing A. thaliana for further analysis, the defensin pathway was enriched, showing additional signaling and regulation molecules, and how they respond to each other in the modulation of this complex plant defense response. CONCLUSIONS: LAITOR4HPC can be used for an efficient text mining based construction of biological networks derived from big data sources, such as MEDLINE abstracts. Time consumption and data input limitations will depend on the available resources at the HPC facility. LAITOR4HPC enables enough flexibility for different approaches and data amounts targeted to an organism, a subject, or a specific pathway. Additionally, it can deliver comprehensive results where interactions are classified into four types, according to their reliability.

MOTIVATION: Standardization and semantic alignment have been considered one of the major challenges for data integration in clinical research. The inclusion of the CDISC SDTM clinical data standard into the tranSMART i2b2 via a guiding master ontology tree positively impacts and supports the efficacy of data sharing, visualization and exploration across datasets. RESULTS: We present here a schema for the organization of SDTM variables into the tranSMART i2b2 tree along with a script and test dataset to exemplify the mapping strategy. The eTRIKS master tree concept is demonstrated by making use of fictitious data generated for four patients, including 16 SDTM clinical domains. We describe how the usage of correct visit names and data labels can help to integrate multiple readouts per patient and avoid ETL crashes when running a tranSMART loading routine. AVAILABILITY AND IMPLEMENTATION: The eTRIKS Master Tree package and test datasets are publicly available at https://doi.org/10.5281/zenodo.1009098 and a functional demo installation at https://public.etriks.org/transmart/datasetExplorer/ under eTRIKS-Master Tree branch, where the discussed examples can be visualized.

BACKGROUND: For large international research consortia, such as those funded by the European Union's Horizon 2020 programme or the Innovative Medicines Initiative, good data coordination practices and tools are essential for the successful collection, organization and analysis of the resulting data. Research consortia are attempting ever more ambitious science to better understand disease, by leveraging technologies such as whole genome sequencing, proteomics, patient-derived biological models and computer-based systems biology simulations. RESULTS: The IMI eTRIKS consortium is charged with the task of developing an integrated knowledge management platform capable of supporting the complexity of the data generated by such research programmes. In this paper, using the example of the OncoTrack consortium, we describe a typical use case in translational medicine. The tranSMART knowledge management platform was implemented to support data from observational clinical cohorts, drug response data from cell culture models and drug response data from mouse xenograft tumour models. The high dimensional (omics) data from the molecular analyses of the corresponding biological materials were linked to these collections, so that users could browse and analyse these to derive candidate biomarkers. CONCLUSIONS: In all these steps, data mapping, linking and preparation are handled automatically by the tranSMART integration platform. Therefore, researchers without specialist data handling skills can focus directly on the scientific questions, without spending undue effort on processing the data and data integration, which are otherwise a burden and the most time-consuming part of translational research data analysis.

SUMMARY: In translational research, efficient knowledge exchange between the different fields of expertise is crucial. An open platform that is capable of storing a multitude of data types such as clinical, pre-clinical or OMICS data combined with strong visual analytical capabilities will significantly accelerate the scientific progress by making data more accessible and hypothesis generation easier. The open data warehouse tranSMART is capable of storing a variety of data types and has a growing user community including both academic institutions and pharmaceutical companies. tranSMART, however, currently lacks interactive and dynamic visual analytics and does not permit any post-processing interaction or exploration. For this reason, we developed SmartR , a plugin for tranSMART, that equips the platform not only with several dynamic visual analytical workflows, but also provides its own framework for the addition of new custom workflows. Modern web technologies such as D3.js or AngularJS were used to build a set of standard visualizations that were heavily improved with dynamic elements. AVAILABILITY AND IMPLEMENTATION: The source code is licensed under the Apache 2.0 License and is freely available on GitHub: https://github.com/transmart/SmartR . CONTACT: [email protected]. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

BACKGROUND: Biological function is greatly dependent on the interactions of proteins with other proteins and genes. Abstracts from the biomedical literature stored in the NCBI's PubMed database can be used for the derivation of interactions between genes and proteins by identifying the co-occurrences of their terms. Often, the amount of interactions obtained through such an approach is large and may mix processes occurring in different contexts. Current tools do not allow studying these data with a focus on concepts of relevance to a user, for example, interactions related to a disease or to a biological mechanism such as protein aggregation. RESULTS: To help the concept-oriented exploration of such data we developed PESCADOR, a web tool that extracts a network of interactions from a set of PubMed abstracts given by a user, and allows filtering the interaction network according to user-defined concepts. We illustrate its use in exploring protein aggregation in neurodegenerative disease and in the expansion of pathways associated to colon cancer. CONCLUSIONS: PESCADOR is a platform independent web resource available at: http://cbdm.mdc-berlin.de/tools/pescador/

BACKGROUND: Biological knowledge is represented in scientific literature that often describes the function of genes/proteins (bioentities) in terms of their interactions (biointeractions). Such bioentities are often related to biological concepts of interest that are specific of a determined research field. Therefore, the study of the current literature about a selected topic deposited in public databases, facilitates the generation of novel hypotheses associating a set of bioentities to a common context. RESULTS: We created a text mining system (LAITOR: Literature Assistant for Identification of Terms co-Occurrences and Relationships) that analyses co-occurrences of bioentities, biointeractions, and other biological terms in MEDLINE abstracts. The method accounts for the position of the co-occurring terms within sentences or abstracts. The system detected abstracts mentioning protein-protein interactions in a standard test (BioCreative II IAS test data) with a precision of 0.82-0.89 and a recall of 0.48-0.70. We illustrate the application of LAITOR to the detection of plant response genes in a dataset of 1000 abstracts relevant to the topic. CONCLUSIONS: Text mining tools combining the extraction of interacting bioentities and biological concepts with network displays can be helpful in developing reasonable hypotheses in different scientific backgrounds.

BACKGROUND: Modern proteomes evolved by modification of pre-existing ones. It is extremely important to comparative biology that related proteins be identified as members of the same cognate group, since a characterized putative homolog could be used to find clues about the function of uncharacterized proteins from the same group. Typically, databases of related proteins focus on those from completely-sequenced genomes. Unfortunately, relatively few organisms have had their genomes fully sequenced; accordingly, many proteins are ignored by the currently available databases of cognate proteins, despite the high amount of important genes that are functionally described only for these incomplete proteomes. RESULTS: We have developed a method to cluster cognate proteins from multiple organisms beginning with only one sequence, through connectivity saturation with that Seed sequence. We show that the generated clusters are in agreement with some other approaches based on full genome comparison. CONCLUSION: The method produced results that are as reliable as those produced by conventional clustering approaches. Generating clusters based only on individual proteins of interest is less time consuming than generating clusters for whole proteomes.