We have been busy working off-site for over a year and are getting ready to transition back to the office. We have a new Chair – Yves Lussier, which has freed up some of my time. Here are some updates from the past few months.
Students:
- We have a SPUR undergraduate working with us for the Summer. Welcome to Kiley Hewitt.
- Michael Watkins is wrapping up ready to defend. Michael presented another paper at the AMIA Summit meeting this Spring.
Newborn screening (NBS) can be life-changing for the families of infants who test positive for a rare condition. While resources exist to support these families, there can be delays in sharing these resources due to communication lag between the laboratory, result interpreting clinician, family of the newborn, and additional care providers. This delay can also be exacerbated when additional health history is required from the mother and infant. ResultsMyWay is a proof-of-concept application that uses clinical quality language (CQL) to automate the search for this additional health history. It also translates the NBS results into Fast Healthcare Interoperability Resources (FHIR), increasing both the ease of exchange and the future utility of these data points. After the families are given the NBS results, ResultsMyWay then acts as a hub for several types of informational resources about the recently diagnosed condition.
Recent Papers:
- Ruiz-Schultz N, Sant D, Norcross S, Dansithong W, Hart K, Asay B, Little J, Chung K, Oakeson KF, Young EL, Eilbeck K, Rohrwasser A. Methods and feasibility study for exome sequencing as a universal second-tier test in newborn screening. Genet Med. 2021 Apr;23(4):767-776. doi: 10.1038/s41436-020-01058-w. Epub 2021 Jan 13. PMID: 33442025.
Purpose: Newborn screening disorders increasingly require genetic variant analysis as part of second-tier or confirmatory testing. Sanger sequencing and gene-specific next-generation sequencing (NGS)-based tests, the current methods of choice, are costly and lack scalability when expanding to new conditions. We describe a scalable, exome sequencing-based NGS pipeline with a priori analysis restriction that can be universally applied to any NBS disorder.
Methods: De-identified abnormal newborn screening specimens representing severe combined immune deficiency (SCID), cystic fibrosis (CF), VLCAD deficiency, metachromatic leukodystrophy (MLD), and in silico sequence read data sets were used to validate the pipeline. To support interpretation and clinical decision-making within the bioinformatics pipeline, variants from multiple databases were curated and validated.
Results: CFTR variant panel analysis correctly identified all variants. Concordance compared with diagnostic testing results for targeted gene analysis was between 78.6% and 100%. Validation of the bioinformatics pipeline with in silico data sets revealed a 100% detection rate. Varying degrees of overlap were observed between ClinVar and other databases ranging from 3% to 65%. Data normalization revealed that 11% of variants across the databases required manual curation.
Conclusion: This pipeline allows for restriction of analysis to variants within a single gene or multiple genes, and can be readily expanded to full exome analysis if clinically indicated and parental consent is granted. - Lario R, Hasley S, White SA, Eilbeck K, Soley R, Huff S, Kawamoto K. Utilization of BPM+ Health for the Representation of Clinical Knowledge: A Framework for the Expression and Assessment of Clinical Practice Guidelines (CPG) Utilizing Existing and Emerging Object Management Group (OMG) Standards. AMIA Annu Symp Proc. 2021 Jan 25;2020:687-696. PMID: 33936443; PMCID: PMC8075494.
Clinical Practice Guidelines (CPG), meant to express best practices in healthcare, are commonly presented as narrative documents communicating care processes, decision making, and clinical case knowledge. However, these narratives in and of themselves lack the specificity and conciseness in their use of language to unambiguously express quality clinical recommendations. This impacts the confidence of clinicians, uptake, and implementation of the guidance. As important as the quality of the clinical knowledge articulated, is the quality of the language(s) and methods used to express the recommendations. In this paper, we propose the BPM+ family of modeling languages as a potential solution to this challenge. We present a formalized process and framework for translating CPGs into a standardized BPM+ model. Further, we discuss the features and characteristics of modeling languages that underpin the quality in expressing clinical recommendations. Using an existing CPG, we defined a systematic series of steps to deconstruct the CPG into knowledge constituents, assign CPG knowledge constituents to BPM+ elements, and re-assemble the parts into a clear, precise, and executable model. Limitations of both the CPG and the current BPM+ languages are discussed.
Grants:
We just got the notice of award on our Computational Approaches to Diabetes and Metabolism from the NIDDK. I am thrilled to lead this effort to bring informatics education to students focused on truly important metabolic problems. This is a renewal for this grant and one of the nice things about it is a dual mentor system that is good for the students and opens up new areas of research for faculty.
Education:
This Spring semester I worked with Domian Borbolla (DBMI) and others to develop introductory Health System Science Data and deploy it in game format in the Med School course that I co-direct. This new way to get engagement in what can be quite dry material was refreshing. The work was sponsored by the AMA.
Conferences:
We are getting ready to start moving around again and have been busy submitting to AMIA, the APHL newborn screening conference and ASRM. I am quite excited about the new incarnation of the AMIA Education Forum.