Model, Integrate, Search... Repeat : A Sound Approach to Building Integrated Repositories of Genomic Data

This book is a revised version of the PhD dissertation written by the author to receive her PhD from the Department of Electronics, Information and Bioengineering at Politecnico di Milano, Italy. The work deals with one of the central objectives of the European Research Council project “Data-Driven Genomic Computing”, i.e., building an integrated repository for genomic data. It reflects the research adventure that starts from modeling biological data, goes through the challenges of integrating complex data and their describing metadata and finally builds tools for searching the data empowered by a semantic layer. The results of this thesis are part of a broad vision: the availability of conceptual models, related databases, and search systems for both humans and viruses genomics will provide important opportunities for research, especially if virus data will be connected to its host, the human being, who is the provider of genomic and phenotype information. In 2023, the PhD dissertation won the CAiSE PhD Award, granted to outstanding PhD theses in the field of information systems engineering. Foreword Preface Acknowledgements Contents Acronyms Introduction Genomic Data Integration Thesis Contribution within the GeCo Project The Recent COVID-19 Pandemic Thesis Structure Part I Human Genomic Data Integration Genomic Data Players and Processes Technological Pipeline of Genomic Data Production Integration Services and Access Taxonomy of Players Involved in Data Production and Integration Main Genomic Data Players Contributors Repository Hosts Consortia Integrators Modeling Genomic Data The Genomic Data Model The Genomic Conceptual Model Analysis of Metadata Attributes Model Design Validation: Source-Specific Views of GCM Related Works Integrating Genomic Data Theoretical Rationale Approach Overview Data Download Data Transformation Data Cleaning Data Mapping Data Normalization and Enrichment Search Service and Ontology Selection Enrichment Process Data Constraint Checking Architecture Implementation Data Persistence Architecture Validation Lossless Integration Semantic Enrichment User Evaluation Related Works Snapshot of the Data Repository Included Data Sources OpenGDC: Integrating Cancer Genomic Data and Metadata Towards Automated Integration of Unstructured Metadata Experiments Related Works Searching Genomic Data Issues in Exploiting Semantic Knowledge in Genomics Inference Explanation GeKnowGraph: Exploration-Based Interface Exploration Interaction GenoSurf: a Web-Based Search Server for Genomic Datasets Data Search Key-Value Search Query Sessions Result Visualization Additional Functionalities Use Cases Validation of GenoSurf Related Works Future Directions of the Data Repository Including New Data Sources Improving Genomic Data Quality Dimensions Towards Better Interoperability Simplifying Data and Tools for End Users Monitoring Integration and Search Value Part II Viral Sequence Data Integration Viral Sequences Data Management Resources Landscape of Data Resources for Viral Sequences Fully Open-Source Resources GISAID and its Resources Integration of Sources of Viral Sequences Metadata Integration Value Harmonization and Ontological Efforts Replicated Sequences in Multiple Sources SARS-CoV-2 Search Systems Portals to NCBI and GISAID Resources Integrative Search Systems Comparison Discussion GISAID Restrictions Metadata Quality (Un)Willingness to Share Sequence Data Modeling Viral Sequence Data Conceptual Modeling for Viral Genomics Answering Complex Biological Queries Related Works Integrating Viral Sequence Data Database Content Relational Schema Data Import Annotation and Variant Calling Data Curation Searching Viral Sequence Data Requirements Analysis Lessons Learnt Web Interface Example Queries Discussion Related Works Future Directions of the Viral Sequence Repository Research Agenda ViruSurf Extensions Visualization Support: VirusViz Active Monitoring of SARS-CoV-2 Variations Integrating Host-Pathogen Information The Virus Genotype – Host Phenotype Connection The Host Genotype – Host Phenotype Connection Part III Epilogue Conclusions and Vision Summary of Thesis Contributions Achievements within GeCo Project Outlook META-BASE tool configuration User Manual Process Configuration Mapper Configuration Experimental setup GEO metadata extraction Mappings of viral sources attributes into ViruSurf References