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Classifying diseases by using biological features to identify potential nosological models.

ABSTRACT: Established nosological models have provided physicians an adequate enough classification of diseases so far. Such systems are important to correctly identify diseases and treat them successfully. However, these taxonomies tend to be based on phenotypical observations, lacking a molecular or biological foundation. Therefore, there is an urgent need to modernize them in order to include the heterogeneous information that is produced in the present, as could be genomic, proteomic, transcriptomic and metabolic data, leading this way to more comprehensive and robust structures. For that purpose, we have developed an extensive methodology to analyse the possibilities when it comes to generate new nosological models from biological features. Different datasets of diseases have been considered, and distinct features related to diseases, namely genes, proteins, metabolic pathways and genetical variants, have been represented as binary and numerical vectors. From those vectors, diseases distances have been computed on the basis of several metrics. Clustering algorithms have been implemented to group diseases, generating different models, each of them corresponding to the distinct combinations of the previous parameters. They have been evaluated by means of intrinsic metrics, proving that some of them are highly suitable to cover new nosologies. One of the clustering configurations has been deeply analysed, demonstrating its quality and validity in the research context, and further biological interpretations have been made. Such model was particularly generated by OPTICS clustering algorithm, by studying the distance between diseases based on gene sharedness and following cosine index metric. 729 clusters were formed in this model, which obtained a Silhouette coefficient of 0.43.

SUBMITTER: Prieto Santamaria L

PROVIDER: S-EPMC8548311 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundAn important goal in post-genomic research is discovering the network of interactions between transcription factors (TFs) and the genes they regulate. We have previously reported the development of a supervised-learning approach to TF target identification, and used it to predict targets of 104 transcription factors in yeast. We now include a new sequence conservation measure, expand our predictions to include 59 new TFs, introduce a web-server, and implement an improved ranking method to reveal the biological features contributing to regulation. The classifiers combine 8 genomic datasets covering a broad range of measurements including sequence conservation, sequence overrepresentation, gene expression, and DNA structural properties.Principal findings(1) Application of the method yields an amplification of information about yeast regulators. The ratio of total targets to previously known targets is greater than 2 for 11 TFs, with several having larger gains: Ash1(4), Ino2(2.6), Yaf1(2.4), and Yap6(2.4). (2) Many predicted targets for TFs match well with the known biology of their regulators. As a case study we discuss the regulator Swi6, presenting evidence that it may be important in the DNA damage response, and that the previously uncharacterized gene YMR279C plays a role in DNA damage response and perhaps in cell-cycle progression. (3) A procedure based on recursive-feature-elimination is able to uncover from the large initial data sets those features that best distinguish targets for any TF, providing clues relevant to its biology. An analysis of Swi6 suggests a possible role in lipid metabolism, and more specifically in metabolism of ceramide, a bioactive lipid currently being investigated for anti-cancer properties. (4) An analysis of global network properties highlights the transcriptional network hubs; the factors which control the most genes and the genes which are bound by the largest set of regulators. Cell-cycle and growth related regulators dominate the former; genes involved in carbon metabolism and energy generation dominate the latter.ConclusionPostprocessing of regulatory-classifier results can provide high quality predictions, and feature ranking strategies can deliver insight into the regulatory functions of TFs. Predictions are available at an online web-server, including the full transcriptional network, which can be analyzed using VisAnt network analysis suite.

Project description:BackgroundInformation pertaining to mechanisms, management and treatment of disease-causing pathogens including viruses and bacteria is readily available from research publications indexed in MEDLINE. However, identifying the literature that specifically characterises these pathogens and their properties based on experimental research, important for understanding of the molecular basis of diseases caused by these agents, requires sifting through a large number of articles to exclude incidental mentions of the pathogens, or references to pathogens in other non-experimental contexts such as public health.ObjectiveIn this work, we lay the foundations for the development of automatic methods for characterising mentions of pathogens in scientific literature, focusing on the task of identifying research that involves the experimental study of a pathogen in an experimental context. There are no manually annotated pathogen corpora available for this purpose, while such resources are necessary to support the development of machine learning-based models. We therefore aim to fill this gap, producing a large data set automatically from MEDLINE under some simplifying assumptions for the task definition, and using it to explore automatic methods that specifically support the detection of experimentally studied pathogen mentions in research publications.MethodsWe developed a pathogen mention characterisation literature data set -READBiomed-Pathogens- automatically using NCBI resources, which we make available. Resources such as the NCBI Taxonomy, MeSH and GenBank can be used effectively to identify relevant literature about experimentally researched pathogens, more specifically using MeSH to link to MEDLINE citations including titles and abstracts with experimentally researched pathogens. We experiment with several machine learning-based natural language processing (NLP) algorithms leveraging this data set as training data, to model the task of detecting papers that specifically describe experimental study of a pathogen.ResultsWe show that our data set READBiomed-Pathogens can be used to explore natural language processing configurations for experimental pathogen mention characterisation. READBiomed-Pathogens includes citations related to organisms including bacteria, viruses, and a small number of toxins and other disease-causing agents.ConclusionsWe studied the characterisation of experimentally studied pathogens in scientific literature, developing several natural language processing methods supported by an automatically developed data set. As a core contribution of the work, we presented a methodology to automatically construct a data set for pathogen identification using existing biomedical resources. The data set and the annotation code are made publicly available. Performance of the pathogen mention identification and characterisation algorithms were additionally evaluated on a small manually annotated data set shows that the data set that we have generated allows characterising pathogens of interest.Trial registrationN/A.

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Classifying diseases by using biological features to identify potential nosological models.

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