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Review
. 2023 Feb 27:1:e15.
doi: 10.1017/pcm.2023.3. eCollection 2023.

Building a precision medicine infrastructure at a national level: The Swedish experience

Anders Edsjö  1   2 , Anna Lindstrand  3   4   5 , David Gisselsson  1   6 , Paula Mölling  7 , Mikaela Friedman  3 , Lucia Cavelier  3   4 , Maria Johansson  8 , Hans Ehrencrona  1   6 , Therese Fagerqvist  9 , Tobias Strid  10   11 , Lovisa Lovmar  12 , Bo Jacobsson  13   14 , Åsa Johansson  15 , Lars Engstrand  16 , Craig E Wheelock  17   18 , Per Sikora  12   19   20 , Valtteri Wirta  5   21   22 , Thoas Fioretos  1   6   23 , Richard Rosenquist  3   4   5 ; Genomic Medicine Sweden (GMS)
Affiliations
Review

Building a precision medicine infrastructure at a national level: The Swedish experience

Anders Edsjö et al. Camb Prism Precis Med. .

Abstract

Precision medicine has the potential to transform healthcare by moving from one-size-fits-all to personalised treatment and care. This transition has been greatly facilitated through new high-throughput sequencing technologies that can provide the unique molecular profile of each individual patient, along with the rapid development of targeted therapies directed to the Achilles heels of each disease. To implement precision medicine approaches in healthcare, many countries have adopted national strategies and initiated genomic/precision medicine initiatives to provide equal access to all citizens. In other countries, such as Sweden, this has proven more difficult due to regionally organised healthcare. Using a bottom-up approach, key stakeholders from academia, healthcare, industry and patient organisations joined forces and formed Genomic Medicine Sweden (GMS), a national infrastructure for the implementation of precision medicine across the country. To achieve this, Genomic Medicine Centres have been established to provide regionally distributed genomic services, and a national informatics infrastructure has been built to allow secure data handling and sharing. GMS has a broad scope focusing on rare diseases, cancer, pharmacogenomics, infectious diseases and complex diseases, while also providing expertise in informatics, ethical and legal issues, health economy, industry collaboration and education. In this review, we summarise our experience in building a national infrastructure for precision medicine. We also provide key examples how precision medicine already has been successfully implemented within our focus areas. Finally, we bring up challenges and opportunities associated with precision medicine implementation, the importance of international collaboration, as well as the future perspective in the field of precision medicine.

Keywords: genomic medicine; implementation; national infrastructure; precision medicine.

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Conflict of interest statement

A.E. has received honoraria from AstraZeneca, Amgen, Bayer, Diaceutics and Roche. R.R. has received honoraria from AbbVie, AstraZeneca, Illumina, Janssen and Roche. V.W. has received honoraria from Illumina and Roche. A.L. has received honoraria from Illumina. D.G. has received honoraria from Bayer AB. H.E. has received honoraria from AstraZeneca. T.F. is a co-founder, board member and scientific advisor of Qlucore AB and Cantargia AB. B.J. has performed clinical diagnostic trials on NIPT with Natera (ongoing), Vanadis (completed) and Hologic (ongoing) with expenditures reimbursed per patient. The other authors declare no conflicts of interest.

Figures

Figure 1.
Figure 1.
Regional distribution, key services and focus areas. Clinical Genomics (CG) units are located at the seven universities with medical faculties, and Genomic Medicine Centres (GMCs) at the seven university hospitals in Sweden. The National Genomics Platform (NGP), located in Western Sweden (Region Västra Götaland), is a highly competent data lake linked to a dynamic scale out high performance computing cluster. CG provides expertise and services to the research and industrial community, and to GMS. GMS currently encompasses seven diagnosis-specific working groups and five working groups supporting the GMS infrastructure.
Figure 2.
Figure 2.
Schematic view of the National Genomics Platform. The platform is divided into three distinct parts covering storage (NGPr), indexing and metadata analysis (NGPi) and data processing (NGPc). Each GMC has its own tenant within the platform creating the possibility of logical separation between centres. The separation persists in the indexing layer, allowing a fine-grained control over what metadata is shared between centres. The indexing layer can then serve as a back-end for both interpretation tools and national and international data sharing. Data processing can be either local on-prem or provisioned on-demand in one or multiple cloud providers’ platforms.
Figure 3.
Figure 3.
Number of analysed patients using WGS analysis in specific disease groups of rare disease. Positive (light colour) and negative (dark colour) genetic findings with corresponding diagnostic yield above each bar. Based on WGS analysis performed at three GMCs during 2021.
Figure 4.
Figure 4.
Genomic profiling of solid tumours illustrating first- and second-generation gene panels. CNV, copy-number variant; indels, insertions and deletions; SNVs, single nucleotide variants.
Figure 5.
Figure 5.
National strategy for precision diagnostics in haematological malignancies. ALL, acute lymphoblastic leukaemia; AML, acute myeloid leukaemia; CLL, chronic lymphocytic leukaemia; CML, chronic myeloid leukaemia; indels, insertions and deletions; MDS, myelodysplastic syndrome; MPN, myeloproliferative neoplasias; SNVs, single nucleotide variants.
Figure 6.
Figure 6.
Infographics of the GMS Childhood Cancer pipeline. The upper panel outlines the main steps for each patient’s sample and the resulting information: (1) inclusion based on informed consent and tumour cell content in biopsy >40%, (2) WGS of tumour DNA (minimum 90×), normal sample DNA (30×), and tumour RNA-sequencing, (3) filtering of tumour WGS data against normal sample WGS data to identify somatic mutations, (4) further filtering of non-synonymous coding variants against a flexible gene list of somatic mutations of clinical importance in childhood cancer, also including potential druggable targets, (5) fusion gene capture from RNA-sequencing data, (6) creation of whole genome profiles of copy numbers and allelic states, (7) discussion of findings at a molecular tumour board and (8) formulation of a written report, added as a complement to the standard pathology report. The bottom panel itemises passed milestones and future plans.
See this image and copyright information in PMC

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