Empowering genomic medicine by establishing critical sequencing result data flows: the eMERGE example

Aronson, Samuel; Babb, Lawrence; Ames, Darren; Gibbs, Richard A.; Venner, Eric; Connelly, John; Marsolo, Keith; Weng, Chunhua; Williams, Marc S.; Hartzler, Andrea L.; Liang, Wayne H.; Ralston, James D.; Devine, Emily Beth; Murphy, Shawn N.; Chute, Christopher G.; Caraballo, Pedro J.; Kullo, Iftikhar J.; Freimuth, Robert R.; Rasmussen, Luke V.; Wehbe, Firas; Peterson, Josh F.; Robinson, Jamie R.; Wiley, Ken; Taylor, Casey Overby

doi:10.1093/jamia/ocy051

Cited by 22 publications

(21 citation statements)

References 12 publications

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“…Possible difficulties in data sharing between different parts of the network were anticipated and obviated by development of an agreed .xml standard. This standard was based upon the GeneInsight specifications and facilitated communication across all components (See Methods and 17 ).…”

Section: Resultsmentioning

confidence: 99%

Harmonizing Clinical Sequencing And Interpretation For The Emerge III Network

Zouk

Lennon

Rehm

et al. 2018

Preprint

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36Background: The eMERGE III Network was tasked with harmonizing genetic testing protocols linking multiple 37 sites and investigators. 38Methods: DNA capture panels targeting 109 genes and 1551 variants were constructed by two clinical 39 sequencing centers for analysis of 25,000 participant DNA samples collected at 11 sites where samples were 40 linked to patients with electronic health records. Each step from sample collection, data generation, 41 interpretation, reporting, delivery and storage, were developed and validated in CAP/CLIA settings and 42 harmonized across sequencing centers. 43Results: A compliant and secure network was built and enabled ongoing review and reconciliation of clinical 44 interpretations while maintaining communication and data sharing between investigators. Mechanisms for 45 sustained propagation and growth of the network were established. An interim data freeze representing 15,574 46 sequenced subjects, informed the assay performance for a range of variant types, the rate of return of results 47Conclusions: This study established processes for different sequencing sites to harmonize the technical and 51 interpretive aspects of sequencing tests, a critical achievement towards global standardization of genomic 52 testing. The network established experience in the return of results and the rate of secondary findings across 53 diverse biobank populations. Furthermore, the eMERGE network has accomplished integration of structured 54 genomic results into multiple electronic health record systems, setting the stage for clinical decision support to 55 enable genomic medicine. 56 57 58 59 60 61 62The identification, interpretation and return of actionable clinical genetic findings is an increasing focus of 63 precision medicine. There is also growing awareness that the discovery of genes underlying human diseases is 64 dependent upon access to samples from carefully phenotyped individuals with (and without) clinical conditions. 65As clinical visits provide the ideal opportunity to record patient phenotypes, with appropriate consent, the medical 66 care of specific patient groups can drive the accumulation of clinical data and knowledge of the genetic 67 underpinnings of disease and the penetrance of DNA risk variants. This 'virtuous cycle' of data flow from the 68 bench to the bedside and back to the bench will be a key driver of progress in genetic and genomic translation. 69 70 While conceptually straightforward, there are many challenges that must be overcome for integrating clinical and 71 research agendas across global populations. Clinical visits are often brief, focused upon measurement related 72 to specific symptoms and constrained by fiscal and practical concerns. On the other hand, ascertainment for 73research is often open ended, longitudinal, and accompanied by rigorous consent procedures. The types of data 74 that are recorded for each purpose can be different in both depth and quality. As a result, ideal research and 75 clinical records often diverge. 76 77A second group of ...

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Section: Resultsmentioning

confidence: 99%

Harmonizing Clinical Sequencing And Interpretation For The Emerge III Network

Zouk

Lennon

Rehm

et al. 2018

Preprint

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“…Clinical genome sequencing has made a major impact on the diagnosis and treatment of a broad range of clinical presentations, notably within the care of cases of pediatric cancer and rare Mendelian disease [1][2][3][4] . Maintaining the security and authenticity of clinical reports containing genetic testing results is an essential component of a clinical laboratory's workflow as they contain protected health information (PHI) as well as genomic findings that impact healthcare [5,6] . As the continuous rapid advancement of genetic understanding necessitates re-review of previous findings there are often updates to clinical reports, resulting in multiple report 'versions' [7,8] .…”

Section: Introductionmentioning

confidence: 99%

“…Communication of report authenticity to individuals who are external to the clinical laboratory who do not have database access, including patients, clinicians and auditors is also challenge. [6] Another approach is to issue signed certificates alongside reports; however, this shifts the problem to tracking the certificates themselves and does not provide a mechanism for determining whether a signed report is the most recent.…”

Section: Introductionmentioning

confidence: 99%

“…ARBoR instead, balances simplicity and precise tracking to singularly solve the report authenticity problem. [6] ARBoR: ARCHITECTURE AND DESIGN The A uthenticated R esources in Chained B l o ck R egistry (ARBoR) system ( Figure 1 ) implements a replicated ledger of cryptographically-signed clinical reports, enabling the institutions receiving those reports to authenticate and establish the report version. The system consists of three parts: first, the ARBoR Service, which is integrated into the reporting laboratory's clinical interpretation and reporting pipeline and is responsible for creating a record in a centralized, publicly-readable ledger for the clinical report and related files.…”

Section: Introductionmentioning

confidence: 99%

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ARBoR: An Identity and Security Solution for Clinical Reporting

Murugan

Hale

Jones

et al. 2019

Preprint

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Motivation : Clinical genome sequencing laboratories return reports containing clinical testing results, signed by an Board Certified clinical geneticist, to the ordering physician. This report is often a pdf, but can also be a physical paper copy or a structured data file. The reports are frequently modified and re-issued, due to changes in variant interpretation or clinical attributes. To precisely track report authenticity we developed ARBoR, an application for tracking the lineage of versioned clinical reports even when they are distributed as pdf or paper copies. ARBoR employs a modified blockchain approach and instead of relying on a computationally intensive consensus mechanism for determining authenticity, we allow supervised and digitally signed writes to an encrypted ledger, which is then exactly replicated to many clients.Results : ARBoR was implemented for clinical reporting in the HGSC-CL Clinical Laboratory, initially as part of the NIH's Electronic Medical Record and Genomics (eMERGE) project. To date we have issued 15,205 versioned clinical reports tracked by ARBoR. This system has provided us with a simple and tamper-proof mechanism for tracking clinical reports with a complicated update history.

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“…EMR integration of genetic test results is advancing through the creation of FHIR standards with genomic modules, the eMERGE program at the National Human Genome Research Institute Rand the attention of large EMR companies. 11,12 New models of telehealth genetic counseling have been developed to support both patient and provider consultations. 13 Population health efforts are increasingly recognizing the importance of collecting information on family history.…”

mentioning

confidence: 99%

Calling on Primary Care to Prevent BRCA-Related Cancers

Armstrong

2019

J GEN INTERN MED

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Empowering genomic medicine by establishing critical sequencing result data flows: the eMERGE example

Cited by 22 publications

References 12 publications

Harmonizing Clinical Sequencing And Interpretation For The Emerge III Network

Harmonizing Clinical Sequencing And Interpretation For The Emerge III Network

ARBoR: An Identity and Security Solution for Clinical Reporting

Calling on Primary Care to Prevent BRCA-Related Cancers

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