Lessons learned and recommendations for data coordination in collaborative research: The CSER consortium experience

Muenzen, Kathleen; Amendola, Laura M.; Kauffman, Tia L.; Mittendorf, Kathleen F.; Bensen, Jeannette T.; Chen, Flavia; Green, Richard; Powell, Bradford C.; Kvale, Mark N.; Angelo, Frank; Farnan, Laura; Fullerton, Stephanie M.; Robinson, Jill O.; Li, Tianran; Murali, Priyanka; Lawlor, James M.J.; Ou, Jeffrey; Hindorff, Lucia A.; Jarvik, Gail P.; Crosslin, David R.

doi:10.1016/j.xhgg.2022.100120

Cited by 5 publications

(4 citation statements)

References 34 publications

(39 reference statements)

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“…NYCKidSeq genome VCFs were collected and analyzed at one of two clinical laboratories (the New York Genome Center or Rady Children’s Institute for Genomic Medicine) 19,35 . Briefly, we collaborated with the CSER2 Data Coordination Center 36 to develop a Docker image containing common genomics tools including bcftools v1.9 37 , htslib v1.9, and bedtools v2.30.0. We developed a workflow in Workflow Description Language (WDL) that uses bedtools and bcftools to quality-filter and region-filter VCFs equivalently to our local filtering process as described below in “Cohort Analysis with Clinically Relevant Regions.” The Dockerfile, WDL, and URLs for the deployed image and AnVIL workflow are available at https://github.com/HudsonAlpha/poison_exon_variant_analysis.…”

Section: Methodsmentioning

confidence: 99%

Poison exon annotations improve the yield of clinically relevant variants in genomic diagnostic testing

Felker

Lawlor

Hiatt

et al. 2023

Preprint

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Purpose: Neurodevelopmental disorders (NDDs) often result from rare genetic variation, but genomic testing yield for NDDs remains around 50%, suggesting some clinically relevant rare variants may be missed by standard analyses. Here we analyze poison exons (PEs) which, while often absent from standard gene annotations, are alternative exons whose inclusion results in a premature termination codon. Variants that alter PE inclusion can lead to loss-of-function and may be highly penetrant contributors to disease. Methods: We curated published RNA-seq data from developing mouse cortex to define 1,937 PE regions conserved between humans and mice and potentially relevant to NDDs. We then analyzed variants found by genome sequencing in multiple NDD cohorts. Results: Across 2,999 probands, we found six clinically relevant variants in PE regions that were previously overlooked. Five of these variants are in genes that are part of the sodium voltage-gated channel alpha subunit family (SCN1A, SCN2A, and SCN8A), associated with epilepsies. One variant is in SNRPB, associated with Cerebrocostomandibular Syndrome. These variants have moderate to high computational impact assessments, are absent from population variant databases, and were observed in probands with features consistent with those reported for the associated gene. Conclusion: With only a minimal increase in variant analysis burden (most probands had zero or one candidate PE variants in a known NDD gene, with an average of 0.77 per proband), annotation of PEs can improve diagnostic yield for NDDs and likely other congenital conditions.

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Section: Methodsmentioning

confidence: 99%

Poison exon annotations improve the yield of clinically relevant variants in genomic diagnostic testing

Felker

Lawlor

Hiatt

et al. 2023

Preprint

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“…Developing a database for a study at the onset, before participant recruitment, is worth considering, even for smaller studies. A database can be used to input, edit, store, monitor, and assess data 7. However, the creation of a database system could span weeks to months, depending on the database type used and the study's scope, including the number of research locations, data points, and participant visits.…”

Section: A Study Databasementioning

confidence: 99%

“…A database can be used to input, edit, store, monitor, and assess data. 7 However, the creation of a database system could span weeks to months, depending on the database type used and the study's scope, including the number of research locations, data points, and participant visits. Unfortunately, some researchers anxious to start recording data often opt for paper forms or Microsoft Excel spreadsheets rather than a database program such as REDCap, a web application for building databases and online questionnaires/surveys.…”

Section: A Study Databasementioning

confidence: 99%

An Introduction to Implementing and Conducting the Study

Capili,

Anastasi

2024

AJN, American Journal of Nursing

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Editor's note: This is the 21st article in a series on clinical research by nurses. The series is designed to be used as a resource for nurses to understand the concepts and principles essential to research. Each column will present the concepts that underpin evidence-based practice—from research design to data interpretation. To see all the articles in the series, go to https://links.lww.com/AJN/A204.

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“…While there is some previous empirical research on the governance of health research consortia, this has tended to focus on the power dynamics between institutions from highincome countries and low-or middle-income countries [9][10][11][12][13] or the development of data governance policies within health research consortia [6,8,14]. Further literature draws on authors' experience within consortia to explore the way that conventional governance structures can undermine scientists' ability to implement responsible research and innovation [3], or to propose principles or guidance for consortia governance [1,4].…”

Section: Introductionmentioning

confidence: 99%

Exploring best practice governance for EU-funded health research consortia: A qualitative study protocol for insight and ideation

Renker-Darby,

Bärnighausen,

Neumann

et al. 2023

Preprint

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BackgroundInternational consortia have emerged as a common model to organise and fund large-scale, multi-disciplinary research in contemporary health and biomedical science. The diversity of participants, size and complexity of these consortia necessitates effective governance to achieve their research aims and societal impact. For health research consortia funded by the European Union, certain governance structures and processes have emerged out of convention. However, there is limited scientific evidence to support their use, and little is known about consortia participants’ perspectives on how governance structures could be improved to better serve the implementation of research. In this paper, we present a protocol for a qualitative study to explore the perspectives of participants in European Union-funded health research consortia on the value of governance structures and how they might be improved.Methods and analysisWe will conduct a qualitative study using in-depth interviews with participants in health research consortia funded by the European Union. We will recruit participants following a purposeful sampling approach, and recruitment will continue until saturation is reached. During in-depth interviews, we will ask participants about how the governance of consortia is structured and what is working well or poorly about those governance structures from their perspective. We will draw on design thinking methods to help participants to ideate improvements in governance structures. Data will be analysed using a thematic analysis approach.DiscussionFindings from this study will provide valuable evidence for developing and formulating governance structures for health research consortia. The findings of this work may also contribute to guidelines for consortium proposal submissions.

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Lessons learned and recommendations for data coordination in collaborative research: The CSER consortium experience

Cited by 5 publications

References 34 publications

Poison exon annotations improve the yield of clinically relevant variants in genomic diagnostic testing

Poison exon annotations improve the yield of clinically relevant variants in genomic diagnostic testing

An Introduction to Implementing and Conducting the Study

Exploring best practice governance for EU-funded health research consortia: A qualitative study protocol for insight and ideation

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