Distributed Cognition and Process Management Enabling Individualized Translational Research: The NIH Undiagnosed Diseases Program Experience

Abstract

The National Institutes of Health Undiagnosed Diseases Program (NIH UDP) applies translational research systematically to diagnose patients with undiagnosed diseases. The challenge is to implement an information system enabling scalable translational research. The authors hypothesized that similar complex problems are resolvable through process management and the distributed cognition of communities. The team, therefore, built the NIH UDP integrated collaboration system (UDPICS) to form virtual collaborative multidisciplinary research networks or communities. UDPICS supports these communities through integrated process management, ontology-based phenotyping, biospecimen management, cloud-based genomic analysis, and an electronic laboratory notebook. UDPICS provided a mechanism for efficient, transparent, and scalable translational research and thereby addressed many of the complex and diverse research and logistical problems of the NIH UDP. Full definition of the strengths and deficiencies of UDPICS will require formal qualitative and quantitative usability and process improvement measurement.

Defining Disease, Diagnosis, and Translational Medicine within a Homeostatic Perturbation Paradigm: The National Institutes of Health Undiagnosed Diseases Program Experience

“…These software programs compare HPO terms to similar phenotypic profiles in humans and model organisms, improving prioritization of candidate disease variants. Illustrating the utility of this approach, reanalysis of UDP patient sequence data with Exomiser identified about 10–20% additional molecular diagnoses compared to those identified by manual curation alone ( 19 ).…”

“…This strategy also facilitated prioritizing of sequence variants within gene networks seeded by genes giving similar phenotypes when mutated in humans or model organisms and was effective for identifying atypical presentations ( 18 , 37 ). A tool enabling such analysis is Exome Walker ( 38 ), which is incorporated into Exomiser for exome sequence analysis ( 19 ). This method prioritized mutations in MED23 and UNC80 as likely causes of neurodevelopmental disorders prior to mutations being reported in other families ( 19 , 39 , 40 ).…”

“…A tool enabling such analysis is Exome Walker ( 38 ), which is incorporated into Exomiser for exome sequence analysis ( 19 ). This method prioritized mutations in MED23 and UNC80 as likely causes of neurodevelopmental disorders prior to mutations being reported in other families ( 19 , 39 , 40 ).…”

“…To address these needs, the NIH UDP constructed an integrated system of inventory and data and process management, the Undiagnosed Diseases Program Integrated Collaboration System (UDPICS) (19). This system accumulates an inventory of all biospecimens and associated metadata at the time of collection.…”

“…Performance of translational research requires knowledge and understanding of the problem: what has been tried to address the problem, what has been completed, and what reagents are available. To address these needs, the NIH UDP constructed an integrated system of inventory and data and process management, the Undiagnosed Diseases Program Integrated Collaboration System (UDPICS) ( 19 ). This system accumulates an inventory of all biospecimens and associated metadata at the time of collection.…”