Ontology-guided data preparation for discovering genotype-phenotype relationships

International audienceComplexity of post-genomic data and multiplicity of mining strategies are two limits to Knowledge Discovery in Databases (KDD) in life sciences. Because they provide a semantic frame to data and because they benefit from the progress of semantic web technologies, bio-ontologies should be considered for playing a key role in the KDD process. In the frame of a case study relative to the search of genotype-phenotype relationships, we demonstrate the capability of bio-ontologies to guide data selection during the preparation step of the KDD process. We propose three scenarios to illustrate how domain knowledge can be taken into account in order to select or aggregate data to mine, and consequently how it can facilitate result interpretation at the end of the process

The Coron System

Coron is a domain and platform independent, multi-purposed data mining toolkit, which incorporates not only a rich collection of data mining algorithms, but also allows a number of auxiliary operations. To the best of our knowledge, a data mining toolkit designed specifically for itemset extraction and association rule generation like Coron does not exist elsewhere. Coron also provides support for preparing and filtering data, and for interpreting the extracted units of knowledge

Querying phenotype-genotype relationships on patient datasets using semantic web technology: the example of cerebrotendinous xanthomatosis

Background: Semantic Web technology can considerably catalyze translational genetics and genomics research in medicine, where the interchange of information between basic research and clinical levels becomes crucial. This exchange involves mapping abstract phenotype descriptions from research resources, such as knowledge databases and catalogs, to unstructured datasets produced through experimental methods and clinical practice. This is especially true for the construction of mutation databases. This paper presents a way of harmonizing abstract phenotype descriptions with patient data from clinical practice, and querying this dataset about relationships between phenotypes and genetic variants, at different levels of abstraction. Methods: Due to the current availability of ontological and terminological resources that have already reached some consensus in biomedicine, a reuse-based ontology engineering approach was followed. The proposed approach uses the Ontology Web Language (OWL) to represent the phenotype ontology and the patient model, the Semantic Web Rule Language (SWRL) to bridge the gap between phenotype descriptions and clinical data, and the Semantic Query Web Rule Language (SQWRL) to query relevant phenotype-genotype bidirectional relationships. The work tests the use of semantic web technology in the biomedical research domain named cerebrotendinous xanthomatosis (CTX), using a real dataset and ontologies. Results: A framework to query relevant phenotype-genotype bidirectional relationships is provided. Phenotype descriptions and patient data were harmonized by defining 28 Horn-like rules in terms of the OWL concepts. In total, 24 patterns of SWQRL queries were designed following the initial list of competency questions. As the approach is based on OWL, the semantic of the framework adapts the standard logical model of an open world assumption. Conclusions: This work demonstrates how semantic web technologies can be used to support flexible representation and computational inference mechanisms required to query patient datasets at different levels of abstraction. The open world assumption is especially good for describing only partially known phenotype-genotype relationships, in a way that is easily extensible. In future, this type of approach could offer researchers a valuable resource to infer new data from patient data for statistical analysis in translational research. In conclusion, phenotype description formalization and mapping to clinical data are two key elements for interchanging knowledge between basic and clinical research.The work presented in this paper has been developed in the funded national project Gestión de Terminologías Médicas para Arquetipos (TIN2009-14159-C05-05) by the Ministerio de Educación y Ciencia. This work was partly supported by the network REGENPSI (2009/019) from the Program of Consolidation and Structure of Competitive Units, Consellería de Educación e Ordenación Universitaria, Xunta de Galicia, and by FEDER funds for regional development. PNR was supported by a grant from the Deutsche Forschungsgemeinschaft (DFGRO2005/4-2)S

Multidimensional ontology modeling of human digital ecosystems affected by social behavioural data patterns

Relational and hierarchical data modeling studies are carried out, using simple and explicit comparison based ontology. The comparison is basically performed on relationally and hierarchically structured data entities/dimensions.This methodology is adopted to understand the human ecosystem that is affected by human behavioural and social disorder data patterns. For example, the comparison may be made among human systems, which could be between male and female, fat and slim, disabled and normal (physical impairment), again normal and abnormal (psychological), smokers and non-smokers and among different age group domains.There could be different hierarchies among which, different super-type dimensions are conceptualized into several subtype dimensions and integrated them by connecting the interrelated several common data attributes. Domain ontologies are built based on the known-knowledge mining and thus unknownrelationships are modeled that are affected by social behaviour data patterns. This study is useful in understanding human situations, behavioral patterns and social ecology that can facilitate health and medical practitioners, social workers and psychologists, while treating their patients and clients

Statistical Methods in Integrative Genomics

Statistical methods in integrative genomics aim to answer important biology questions by jointly analyzing multiple types of genomic data (vertical integration) or aggregating the same type of data across multiple studies (horizontal integration). In this article, we introduce different types of genomic data and data resources, and then review statistical methods of integrative genomics, with emphasis on the motivation and rationale of these methods. We conclude with some summary points and future research directions

A Semantic Web for bioinformatics: goals, tools, systems, applications

The quantity of biological information is increasing at an impressive rate. An integrated access to this huge amount of information requires complex search and retrieval software and automation of analysis processes. Automation of integration procedures mainly concerns how to link data, how to select and extract information and how to pipe retrieval and analysis steps. This automated approach to data analysis requires the adoption of new technologies and tools in the bioinformatics domain

Linking Human Diseases to Animal Models Using Ontology-Based Phenotype Annotation

A novel method for quantifying the similarity between phenotypes by the use of ontologies can be used to search for candidate genes, pathway members, and human disease models on the basis of phenotypes alone

From Theory to Practice: A Data Quality Framework for Classification Tasks

The data preprocessing is an essential step in knowledge discovery projects. The experts affirm that preprocessing tasks take between 50% to 70% of the total time of the knowledge discovery process. In this sense, several authors consider the data cleaning as one of the most cumbersome and critical tasks. Failure to provide high data quality in the preprocessing stage will significantly reduce the accuracy of any data analytic project. In this paper, we propose a framework to address the data quality issues in classification tasks DQF4CT. Our approach is composed of: (i) a conceptual framework to provide the user guidance on how to deal with data problems in classification tasks; and (ii) an ontology that represents the knowledge in data cleaning and suggests the proper data cleaning approaches. We presented two case studies through real datasets: physical activity monitoring (PAM) and occupancy detection of an office room (OD). With the aim of evaluating our proposal, the cleaned datasets by DQF4CT were used to train the same algorithms used in classification tasks by the authors of PAM and OD. Additionally, we evaluated DQF4CT through datasets of the Repository of Machine Learning Databases of the University of California, Irvine (UCI). In addition, 84% of the results achieved by the models of the datasets cleaned by DQF4CT are better than the models of the datasets authors.This work has also been supported by: Project: “Red de formación de talento humano para la innovación social y productiva en el Departamento del Cauca InnovAcción Cauca”. Convocatoria 03-2018 Publicación de artículos en revistas de alto impacto. Project: “Alternativas Innovadoras de Agricultura Inteligente para sistemas productivos agrícolas del departamento del Cauca soportado en entornos de IoT - ID 4633” financed by Convocatoria 04C–2018 “Banco de Proyectos Conjuntos UEES-Sostenibilidad” of Project “Red de formación de talento humano para la innovación social y productiva en el Departamento del Cauca InnovAcción Cauca”. Spanish Ministry of Economy, Industry and Competitiveness (Projects TRA2015-63708-R and TRA2016-78886-C3-1-R)

Role of network topology based methods in discovering novel gene-phenotype associations

The cell is governed by the complex interactions among various types of biomolecules. Coupled with environmental factors, variations in DNA can cause alterations in normal gene function and lead to a disease condition. Often, such disease phenotypes involve coordinated dysregulation of multiple genes that implicate inter-connected pathways. Towards a better understanding and characterization of mechanisms underlying human diseases, here, I present GUILD, a network-based disease-gene prioritization framework. GUILD associates genes with diseases using the global topology of the protein-protein interaction network and an initial set of genes known to be implicated in the disease. Furthermore, I investigate the mechanistic relationships between disease-genes and explain the robustness emerging from these relationships. I also introduce GUILDify, an online and user-friendly tool which prioritizes genes for their association to any user-provided phenotype. Finally, I describe current state-of-the-art systems-biology approaches where network modeling has helped extending our view on diseases such as cancer.La cèl•lula es regeix per interaccions complexes entre diferents tipus de biomolècules. Juntament amb factors ambientals, variacions en el DNA poden causar alteracions en la funció normal dels gens i provocar malalties. Sovint, aquests fenotips de malaltia involucren una desregulació coordinada de múltiples gens implicats en vies interconnectades. Per tal de comprendre i caracteritzar millor els mecanismes subjacents en malalties humanes, en aquesta tesis presento el programa GUILD, una plataforma que prioritza gens relacionats amb una malaltia en concret fent us de la topologia de xarxe. A partir d’un conjunt conegut de gens implicats en una malaltia, GUILD associa altres gens amb la malaltia mitjancant la topologia global de la xarxa d’interaccions de proteïnes. A més a més, analitzo les relacions mecanístiques entre gens associats a malalties i explico la robustesa es desprèn d’aquesta anàlisi. També presento GUILDify, un servidor web de fácil ús per la priorització de gens i la seva associació a un determinat fenotip. Finalment, descric els mètodes més recents en què el model•latge de xarxes ha ajudat extendre el coneixement sobre malalties complexes, com per exemple a càncer