Improving the Semantics of a Conceptual Schema of the Human Genome by Incorporating the Modeling of SNPs

The goal of this work is to describe the advantages of the application of Conceptual Modeling (CM) in complex domains, such as genomics. Nowadays, the study and comprehension of the human genome is a major challenge due to its high level of complexity. The constant evolution in the genomic domain contributes to the generation of ever larger amounts of new data, which means that if we do not manage it correctly data quality could be compromised (i.e., problems related with heterogeneity and inconsistent data). In this paper, we propose the use of a Conceptual Schema of the Human Genome (CSHG), designed to understand and improve our ontological commitment to the domain and also extend (enrich) this schema with the integration of a novel concept: Haplotypes. Our focus is on improving the understanding of the relationship between genotype and phenotype, since new findings show that this question is more complex than was originally thought. Here we present the first steps in our data management approach with haplotypes (variations, frequencies and populations) and discuss the database evolution to support this data. Each new version in our conceptual schema (CS) introduces changes to the underlying database structure that has essential and practical implications for better understanding and managing the relevant information. A solution based on conceptual models gives a clear definition of the domain with direct implications in the medical field (Precision Medicine), in which Genomic Information Systems (GeIS) play a very important role.

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Applying the Principles of an Ontology-Based Approach to a Conceptual Schema of Human Genome

Conceptual Modeling - Lecture Notes in Computer Science ◽

10.1007/978-3-642-41924-9_40 ◽

2013 ◽

pp. 471-478 ◽

Cited By ~ 4

Author(s):

Ana Ma Martínez Ferrandis ◽

Oscar Pastor López ◽

Giancarlo Guizzardi

Keyword(s):

Human Genome ◽

Conceptual Schema

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On how to generalize species-specific conceptual schemes to generate a species-independent Conceptual Schema of the Genome

BMC Bioinformatics ◽

10.1186/s12859-021-04237-x ◽

2021 ◽

Vol 22 (S13) ◽

Author(s):

Alberto García S. ◽

Juan Carlos Casamayor

Keyword(s):

Human Genome ◽

Conceptual Modeling ◽

Genetic Diagnosis ◽

Use Cases ◽

Use Case ◽

Conceptual Schema ◽

Conceptual Schemes ◽

Modeling Techniques ◽

Species Specific ◽

Specific Species

Abstract Background Understanding the genome, with all of its components and intrinsic relationships, is a great challenge. Conceptual modeling techniques have been used as a means to face this challenge. The heterogeneity and idiosyncrasy of genomic use cases mean that conceptual modeling techniques are used to generate conceptual schemes that focus on too specific scenarios (i.e., they are species-specific conceptual schemes). Our research group developed two different conceptual schemes. The first one is the Conceptual Schema of the Human Genome, which is intended to improve Precision Medicine and genetic diagnosis. The second one is the Conceptual Schema of the Citrus Genome, which is intended to identify the genetic cause of relevant phenotypes in the agri-food field. Methods Our two conceptual schemes have been ontologically compared to identify their similarities and differences. Based on this comparison, several changes have been performed in the Conceptual Schema of the Human Genome in order to obtain the first version of a species-independent Conceptual Schema of the Genome. Identifying the different genome information items used in each genomic case study has been essential in achieving our goal. The changes needed to provide an expanded, more generic version of the Conceptual Schema of the Human Genome are analyzed and discussed. Results This work presents a new CS called the Conceptual Schema of the Genome that is ready to be adapted to any specific working genome-based context (i.e., species-independent). Conclusion The generated Conceptual Schema of the Genome works as a global, generic element from which conceptual views can be created in order to work with any specific species. This first working version can be used in the human use case, in the citrus use case, and, potentially, in more use cases of other species.

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DNA methylation in satellite repeats disorders

Essays in Biochemistry ◽

10.1042/ebc20190028 ◽

2019 ◽

Vol 63 (6) ◽

pp. 757-771 ◽

Cited By ~ 4

Author(s):

Claire Francastel ◽

Frédérique Magdinier

Keyword(s):

Dna Methylation ◽

Human Genome ◽

Repetitive Dna ◽

Dna Sequences ◽

Satellite Repeats ◽

Tremendous Progress ◽

Genes Encoding ◽

Dna Elements ◽

Near Future

Abstract Despite the tremendous progress made in recent years in assembling the human genome, tandemly repeated DNA elements remain poorly characterized. These sequences account for the vast majority of methylated sites in the human genome and their methylated state is necessary for this repetitive DNA to function properly and to maintain genome integrity. Furthermore, recent advances highlight the emerging role of these sequences in regulating the functions of the human genome and its variability during evolution, among individuals, or in disease susceptibility. In addition, a number of inherited rare diseases are directly linked to the alteration of some of these repetitive DNA sequences, either through changes in the organization or size of the tandem repeat arrays or through mutations in genes encoding chromatin modifiers involved in the epigenetic regulation of these elements. Although largely overlooked so far in the functional annotation of the human genome, satellite elements play key roles in its architectural and topological organization. This includes functions as boundary elements delimitating functional domains or assembly of repressive nuclear compartments, with local or distal impact on gene expression. Thus, the consideration of satellite repeats organization and their associated epigenetic landmarks, including DNA methylation (DNAme), will become unavoidable in the near future to fully decipher human phenotypes and associated diseases.

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