SwissGenVar: A Platform for Clinical-Grade Interpretation of Genetic Variants to Foster Personalized Healthcare in Switzerland

Large-scale next-generation sequencing (NGS) germline testing is technically feasible today, but variant interpretation represents a major bottleneck in analysis workflows. This includes extensive variant prioritization, annotation, and time-consuming evidence curation. The scale of the interpretation problem is massive, and variants of uncertain significance (VUSs) are a challenge to personalized medicine. This challenge is further compounded by the complexity and heterogeneity of the standards used to describe genetic variants and the associated phenotypes when searching for relevant information to support clinical decision making. To address this, all five Swiss academic institutions for Medical Genetics joined forces with the Swiss Institute of Bioinformatics (SIB) to create SwissGenVar as a user-friendly nationwide repository and sharing platform for genetic variant data generated during routine diagnostic procedures and research sequencing projects. Its aim is to provide a protected environment for expert evidence sharing about individual variants to harmonize and upscale their significance interpretation at the clinical grade according to international standards. To corroborate the clinical assessment, the variant-related data will be combined with consented high-quality clinical information. Broader visibility will be achieved by interfacing with international databases, thus supporting global initiatives in personalized healthcare

SwissGenVar: A platform for clinical grade interpretation of genetic variants to foster personalized health care in Switzerland

Large-scale next-generation sequencing (NGS) germline testing is technically feasible today, but variant interpretation represents a major bottleneck in analysis workflows including the extensive variant prioritization, annotation, and time-consuming evidence curation. The scale of the interpretation problem is massive, and variants of uncertain significance (VUS) are a challenge to personalized medicine. This challenge is further compounded by the complexity and heterogeneity of standards used to describe genetic variants and associated phenotypes when searching for relevant information to inform clinical decision-making. For this purpose, all five Swiss academic Medical Genetics Institutions joined forces with the Swiss Institute of Bioinformatics (SIB) to create SwissGenVar as a user-friendly nationwide repository and sharing platform for genetic variant data generated during routine diagnostic procedures and research sequencing projects. Its objective is to provide a protected environment for expert evidence sharing about individual variants to harmonize and up-scale their significance interpretation at clinical grade following international standards. To corroborate the clinical assessment, the variant-related data are combined with consented high-quality clinical information. Broader visibility will be gained by interfacing with international databases, thus supporting global initiatives in personalized health care

Using machine learning methods to improve healthcare delivery in diabetes management

This dissertation includes three studies, all focusing on Analytics and Patients information for improving diabetes management, namely educating patients and early detection of comorbidities. In these studies, we develop topic modeling and artificial neural network to acquire, preprocess, model, and predict to minimize the burden on diabetic patients and healthcare providers.The first essay explores the usage of Text Analytics, an unsupervised machine learning model, utilizing the vast data available on social media to improve diabetes education of the patients in managing the condition. Mainly we show the applicability of topic modeling to identify the gaps in diabetes education content and the information and knowledge needs of the patients. While traditional methods of the content decision were based on a group of experts' contributions, our proposed methodology considers the questions raised on social forums for support to extend the education content.The second essay implements Deep Neural Networks on EHR data to assist the clinicians in rank ordering the potential comorbidities that the specific patient may develop in the future. This essay helps prioritize regular screening for comorbidities and rationalize the screening process to improve adherence and effectiveness. Our model prediction helps identify diabetic retinopathy and nephropathy patients with very high precision compared to other traditional methods. Essays 1 and 2 focus on Data Analytics as a research tool for managing a chronic disease in the healthcare environment.The third essay goes through the challenges and best practices of data preprocessing for Analytics studies in healthcare. This study explores the standard preprocessing methodologies and their impact in the case of healthcare data analytics. Highlights the relevant modifications and adaptations to the standards CRISP_DM process. The suggestions are based on past research and the experience obtained in the projects discussed earlier in the thesis.Overall, the dissertation highlights the importance of data analytics in healthcare for better managing and diagnosing chronic diseases. It unfolds the economic value of implementing state-of-the-art IT methods in healthcare, where EHR & IT are predominantly costly and difficult to implement. The dissertation covers ANN and text mining implementation for diabetes management

Text-Mining Services of the Swiss Variant Interpretation Platform for Oncology

The Swiss Variant Interpretation Platform for Oncology is a centralized, joint and curated database for clinical somatic variants piloted by a board of Swiss healthcare institutions and operated by the SIB Swiss Institute of Bioinformatics. To support this effort, SIB Text Mining designed a set of text analytics services. This report focuses on three of those services. First, the automatic annotations of the literature with a set of terminologies have been performed, resulting in a large annotated version of MEDLINE and PMC. Second, a generator of variant synonyms for single nucleotide variants has been developed using publicly available data resources, as well as patterns of non-standard formats, often found in the literature. Third, a literature ranking service enables to retrieve a ranked set of MEDLINE abstracts given a variant and optionally a diagnosis. The annotation of MEDLINE and PMC resulted in a total of respectively 785,181,199 and 1,156,060,212 annotations, which means an average of 26 and 425 annotations per abstract and full-text article. The generator of variant synonyms enables to retrieve up to 42 synonyms for a variant. The literature ranking service reaches a precision (P10) of 63%, which means that almost two-thirds of the top-10 returned abstracts are judged relevant. Further services will be implemented to complete this set of services, such as a service to retrieve relevant clinical trials for a patient and a literature ranking service for full-text articles.ISSN:0926-9630ISSN:1879-836