Norwegian clinical genetic Analysis Platform (genAP)
The introduction of high-throughput sequencing (HTS) into clinical practice poses great challenges in terms of analytic resources, integration and data security. The project Norwegian clinical genetic Analysis Platform (genAP) was initiated as a response to these challenges, aiming to establish a centralised infrastructure for secure storage and analysis of human sequencing data that allows for disseminated clinical use.
About the project
GenAP is a collaborative project between Oslo University Hospital and the University of Oslo, with implementation of the system in an established high-performance computing environment at the latter. As part of this project, we are in the process of establishing pilot HTS pipelines for a set of clinical packages, each with a defined set of targeted genes. To reduce the workload associated with manual analysis, we are seeking to achieve a high degree of automation, including variant annotation and quality control, filtering based on public resources, identification of previously classified variants, and standardization of report information structure for integration with existing patient journal systems. The figure below gives a schematic overview of the system (a larger version is available here).
Complementing the genetic, bioinformatic and clinical issues, the genAP project also addresses legal, ethical and organizational issues encountered when HTS is deployed in large scale clinical decision making.
We are currently working with three pilot systems. These cover diagnostic, prognostic and pharmacogenetic areas, including cardiomyopathies, breast cancer and adjusting dosage of the immunosuppressive drug tacrolimus in kidney transplantation, respectively. Initially, the pipelines involve targeted capture and resequencing, but the system will be scalable to exome and genome data for a large number of patients. The pilot phase of the project includes comparing the performance of HTS to conventional methods, building a database of genetic variants adapted to our patient populations and real-world testing using collaborating clinicians. The experiences gained will be used to expand to other clinical packages, and the ultimate goal is to introduce the pipelines for widespread use in the clinic.
Participants and project management
GenAP is led by Thomas Grünfeld and involves Professor Dag E. Undlien, Post doc Morten Chr. Eike and MD Lars Retterstøl in our group, as well as research groups at the Department of Informatics, the University Center for Information Technology, the Faculty of Law at the University of Oslo, and the Departement of Pharmacology at Oslo University Hospital. In addition, the project collaborates closely with the Norwegian Sequencing Centre at Ullevål and the clinical section at the Department of Medical Genetics, Oslo University Hospital. The project is supported by grant 210622/O70 from the Research Council of Norway, with funding through 2015.
Eike MC, Lærum H, Hughes T, Håndstad T, Bremer S, Bergan S, Thomassen G, Aanestad M, Grünfeld T, Undlien DE. GenAP: A national platform for clinical genetic analysis of high-throughput sequencing data in Norway. Poster at the American Society of Human Genetics annual meeting, San Francisco, USA, 2012. (pdf).