Recommendations for the integration of genomics into clinical practice

Abstract

The introduction of diagnostic clinical genome and exome sequencing (CGES) is changing the scope of practice for clinical geneticists. Many large institutions are making a significant investment in infrastructure and technology, allowing clinicians to access CGES especially as health care coverage begins to extend to clinically indicated genomic sequencing-based tests. Translating and realizing the comprehensive clinical benefits of genomic medicine remains a key challenge for the current and future care of patients. With the increasing application of CGES, it is necessary for geneticists and other health care providers to understand its benefits and limitations, in order to interpret the clinical relevance of genomic variants identified in the context of health and disease. Establishing new, collaborative working relationships with specialists across diverse disciplines (e.g., clinicians, laboratorians, bioinformaticians) will undoubtedly be key attributes of the future practice of clinical genetics and may serve as an example for other specialties in medicine. These new skills and relationships will also inform the development of the future model of clinical genetics training curricula. To address the evolving role of the clinical geneticist in the rapidly changing climate of genomic medicine, two Clinical Genetics Think Tank meetings were held which brought together physicians, laboratorians, scientists, genetic counselors, trainees and patients with experience in clinical genetics, genetic diagnostics, and genetics education. This paper provides recommendations that will guide the integration of genomics into clinical practice.

The landscape of human mutually exclusive splicing

“…The concerted annotation and splicing analysis of novel exons have deep implications for the detection and interpretation of human disease (Bamshad et al , 2011; Gonzaga‐Jauregui et al , 2012; Xiong et al , 2015; Bowdin et al , 2016). For one, exome and panel sequencing remains the method of choice for the detection of genetic diseases and both methods rely on current exon annotations (Chong et al , 2015).…”

A Review of Recent Advances in Translational Bioinformatics: Bridges from Biology to Medicine

“…The cost structure for computational and analysis resource in genomics points towards the efficiency of developing a single, large center for data analysis and processing. Such a resource would, through virtual access, be combined with a more widely distributed network of expertise [22]. Initiatives such as the European Open Science Cloud will further the creation of infrastructures to enable data sharing and service provision across borders and disciplines 8 .…”

“…For genomic data integration with clinical information, data from primary care, hospitals, outcomes, registries, and social care records should be first recorded using controlled clinical terminologies, such as SNOMED Clinical Terms and the Human Phenotype Ontology [21]. Ontologies as such are not ever complete and end-users such as clinicians will need to work with ontology developers to continuously improve the precision and accuracy of terminologies [22].…”

Review of Clinical Next-Generation Sequencing

“…Issues include making reports understandable, interfacing genomic results with the electronic medical record (EMR), bioinformatics tools to help categorize variants, handling of incidental findings, and whether and how to offer genetic reevaluation. [109][110][111] Other issues include data storage, including what data to store (FASTQ, BAM, variant call file), how long to store data, and how to store large data sets securely. The CAP checklist for NGS provides guidance stating that some files must be stored for at least 2 years; these files should allow re-review of the case in the same manner that allowed generation of the original data.…”