The Global academic research organization network: Data sharing to cure diseases and enable learning health systems.

Introduction:Global data sharing is essential. This is the premise of the Academic Research Organization (ARO) Council, which was initiated in Japan in 2013 and has since been expanding throughout Asia and into Europe and the United States. The volume of data is growing exponentially, providing not only challenges but also the clear opportunity to understand and treat diseases in ways not previously considered. Harnessing the knowledge within the data in a successful way can provide researchers and clinicians with new ideas for therapies while avoiding repeats of failed experiments. This knowledge transfer from research into clinical care is at the heart of a learning health system. Methods:The ARO Council wishes to form a worldwide complementary system for the benefit of all patients and investigators, catalyzing more efficient and innovative medical research processes. Thus, they have organized Global ARO Network Workshops to bring interested parties together, focusing on the aspects necessary to make such a global effort successful. One such workshop was held in Austin, Texas, in November 2017. Representatives from Japan, Taiwan, Singapore, Europe, and the United States reported on their efforts to encourage data sharing and to use research to inform care through learning health systems. Results:This experience report summarizes presentations and discussions at the Global ARO Network Workshop held in November 2017 in Austin, TX, with representatives from Japan, Korea, Singapore, Taiwan, Europe, and the United States. Themes and recommendations to progress their efforts are explored. Standardization and harmonization are at the heart of these discussions to enable data sharing. In addition, the transformation of clinical research processes through disruptive innovation, while ensuring integrity and ethics, will be key to achieving the ARO Council goal to overcome diseases such that people not only live longer but also are healthier and happier as they age. Conclusions:The achievement of global learning health systems will require further exploration, consensus-building, funding aligned with incentives for data sharing, standardization, harmonization, and actions that support global interests for the benefit of patients

Developing a Robust Computable Phenotype Definition Workflow to Describe Health and Disease in Observational Health Research

Health informatics can inform decisions that practitioners, patients, policymakers, and researchers need to make about health and disease. Health informatics is built upon patient health data leading to the need to codify patient health information. Such standardization is required to compute population statistics (such as prevalence, incidence, etc.) that are common metrics used in fields such as epidemiology. Reliable decision-making about health and disease rests on our ability to organize, analyze, and assess data repositories that contain patient health data. While standards exist to structure and analyze patient data across patient data sources such as health information exchanges, clinical data repositories, and health data marketplaces, analogous best practices for rigorously defining patient populations in health informatics contexts do not exist. Codifying best practices for developing disease definitions could support the effective development of clinical guidelines, inform algorithms used in clinical decision support systems, and additional patient guidelines. In this paper, we present a workflow for the development of phenotype definitions. This workflow presents a series of recommendations for defining health and disease. Various examples within this paper are presented to demonstrate this workflow in health informatics contexts.Comment: IEEE Computer Based Medical Systems Conferenc

1st INCF Workshop on Genetic Animal Models for Brain Diseases

The INCF Secretariat organized a workshop to focus on the “role of neuroinformatics in the processes of building, evaluating, and using genetic animal models for brain diseases” in Stockholm, December 13–14, 2009. Eight scientists specialized in the fields of neuroinformatics, database, ontologies, and brain disease participated together with two representatives of the National Institutes of Health and the European Union, as well as three observers of the national INCF nodes of Norway, Poland, and the United Kingdom

Transforming the study of organisms: Phenomic data models and knowledge bases

The rapidly decreasing cost of gene sequencing has resulted in a deluge of genomic data from across the tree of life; however, outside a few model organism databases, genomic data are limited in their scientific impact because they are not accompanied by computable phenomic data. The majority of phenomic data are contained in countless small, heterogeneous phenotypic data sets that are very difficult or impossible to integrate at scale because of variable formats, lack of digitization, and linguistic problems. One powerful solution is to represent phenotypic data using data models with precise, computable semantics, but adoption of semantic standards for representing phenotypic data has been slow, especially in biodiversity and ecology. Some phenotypic and trait data are available in a semantic language from knowledge bases, but these are often not interoperable. In this review, we will compare and contrast existing ontology and data models, focusing on nonhuman phenotypes and traits. We discuss barriers to integration of phenotypic data and make recommendations for developing an operationally useful, semantically interoperable phenotypic data ecosystem

An Evaluation of the Use of a Clinical Research Data Warehouse and I2b2 Infrastructure to Facilitate Replication of Research

Replication of clinical research is requisite for forming effective clinical decisions and guidelines. While rerunning a clinical trial may be unethical and prohibitively expensive, the adoption of EHRs and the infrastructure for distributed research networks provide access to clinical data for observational and retrospective studies. Herein I demonstrate a means of using these tools to validate existing results and extend the findings to novel populations. I describe the process of evaluating published risk models as well as local data and infrastructure to assess the replicability of the study. I use an example of a risk model unable to be replicated as well as a study of in-hospital mortality risk I replicated using UNMC’s clinical research data warehouse. In these examples and other studies we have participated in, some elements are commonly missing or under-developed. One such missing element is a consistent and computable phenotype for pregnancy status based on data recorded in the EHR. I survey local clinical data and identify a number of variables correlated with pregnancy as well as demonstrate the data required to identify the temporal bounds of a pregnancy episode. Next, another common obstacle to replicating risk models is the necessity of linking to alternative data sources while maintaining data in a de-identified database. I demonstrate a pipeline for linking clinical data to socioeconomic variables and indices obtained from the American Community Survey (ACS). While these data are location-based, I provide a method for storing them in a HIPAA compliant fashion so as not to identify a patient’s location. While full and efficient replication of all clinical studies is still a future goal, the demonstration of replication as well as beginning the development of a computable phenotype for pregnancy and the incorporation of location based data in a de-identified data warehouse demonstrate how the EHR data and a research infrastructure may be used to facilitate this effort

A Learning Health Sciences Approach to Understanding Clinical Documentation in Pediatric Rehabilitation Settings

The work presented in this dissertation provides an analysis of clinical documentation that challenges the concepts and thinking surrounding missingness of data from clinical settings and the factors that influence why data are missing. It also foregrounds the critical role of clinical documentation as infrastructure for creating learning health systems (LHS) for pediatric rehabilitation settings. Although completeness of discrete data is limited, the results presented do not reflect the quality of care or the extent of unstructured data that providers document in other locations of the electronic health record (EHR) interface. While some may view imputation and natural language processing as means to address missingness of clinical data, these practices carry biases in their interpretations and issues of validity in results. The factors that influence missingness of discrete clinical data are rooted not just in technical structures, but larger professional, system level and unobservable phenomena that shape provider practices of clinical documentation. This work has implications for how we view clinical documentation as critical infrastructure for LHS, future studies of data quality and health outcomes research, and EHR design and implementation. The overall research questions for this dissertation are: 1) To what extent can data networks be leveraged to build classifiers of patient functional performance and physical disability? 2) How can discrete clinical data on gross motor function be used to draw conclusions about clinical documentation practices in the EHR for cerebral palsy? 3) Why does missingness of discrete data in the EHR occur? To address these questions, a three-pronged approach is used to examine data completeness and the factors that influence missingness of discrete clinical data in an exemplar pediatric data learning network will be used. As a use-case, evaluation of EHR data completeness of gross motor function related data, populated by providers from 2015-2019 for children with cerebral palsy (CP), will be completed. Mixed methods research strategies will be used to achieve the dissertation objectives, including developing an expert-informed and standards-based phenotype model of gross motor function data as a task-based mechanism, conducting quantitative descriptive analyses of completeness of discrete data in the EHR, and performing qualitative thematic analyses to elicit and interpret the latent concepts that contribute to missingness of discrete data in the EHR. The clinical data for this dissertation are sourced from the Shriners Hospitals for Children (SHC) Health Outcomes Network (SHOnet), while qualitative data were collected through interviews and field observations of clinical providers across three care sites in the SHC system.PHDHlth Infrastr & Lrng Systs PhDUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/162994/1/njkoscie_1.pd

Evolutionary Characters, Phenotypes and Ontologies: Curating Data from the Systematic Biology Literature

BACKGROUND: The wealth of phenotypic descriptions documented in the published articles, monographs, and dissertations of phylogenetic systematics is traditionally reported in a free-text format, and it is therefore largely inaccessible for linkage to biological databases for genetics, development, and phenotypes, and difficult to manage for large-scale integrative work. The Phenoscape project aims to represent these complex and detailed descriptions with rich and formal semantics that are amenable to computation and integration with phenotype data from other fields of biology. This entails reconceptualizing the traditional free-text characters into the computable Entity-Quality (EQ) formalism using ontologies. METHODOLOGY/PRINCIPAL FINDINGS: We used ontologies and the EQ formalism to curate a collection of 47 phylogenetic studies on ostariophysan fishes (including catfishes, characins, minnows, knifefishes) and their relatives with the goal of integrating these complex phenotype descriptions with information from an existing model organism database (zebrafish, http://zfin.org). We developed a curation workflow for the collection of character, taxonomic and specimen data from these publications. A total of 4,617 phenotypic characters (10,512 states) for 3,449 taxa, primarily species, were curated into EQ formalism (for a total of 12,861 EQ statements) using anatomical and taxonomic terms from teleost-specific ontologies (Teleost Anatomy Ontology and Teleost Taxonomy Ontology) in combination with terms from a quality ontology (Phenotype and Trait Ontology). Standards and guidelines for consistently and accurately representing phenotypes were developed in response to the challenges that were evident from two annotation experiments and from feedback from curators. CONCLUSIONS/SIGNIFICANCE: The challenges we encountered and many of the curation standards and methods for improving consistency that we developed are generally applicable to any effort to represent phenotypes using ontologies. This is because an ontological representation of the detailed variations in phenotype, whether between mutant or wildtype, among individual humans, or across the diversity of species, requires a process by which a precise combination of terms from domain ontologies are selected and organized according to logical relations. The efficiencies that we have developed in this process will be useful for any attempt to annotate complex phenotypic descriptions using ontologies. We also discuss some ramifications of EQ representation for the domain of systematics

A Review of Current Standards and the Evolution of Histopathology Nomenclature for Laboratory Animals.

The need for international collaboration in rodent pathology has evolved since the 1970s and was initially driven by the new field of toxicologic pathology. First initiated by the World Health Organization's International Agency for Research on Cancer for rodents, it has evolved to include pathology of the major species (rats, mice, guinea pigs, nonhuman primates, pigs, dogs, fish, rabbits) used in medical research, safety assessment, and mouse pathology. The collaborative effort today is driven by the needs of the regulatory agencies in multiple countries, and by needs of research involving genetically engineered animals, for "basic" research and for more translational preclinical models of human disease. These efforts led to the establishment of an international rodent pathology nomenclature program. Since that time, multiple collaborations for standardization of laboratory animal pathology nomenclature and diagnostic criteria have been developed, and just a few are described herein. Recently, approaches to a nomenclature that is amenable to sophisticated computation have been made available and implemented for large-scale programs in functional genomics and aging. Most terminologies continue to evolve as the science of human and veterinary pathology continues to develop, but standardization and successful implementation remain critical for scientific communication now as ever in the history of veterinary nosology

All in the Name: A Review of Current Standards and the Evolution of Histopathological Nomenclature for Laboratory Animals

The need for international collaboration in rodent pathology has evolved since the 1970s, and was initially driven by the new field of toxicologic pathology. First initiated by the World Health Organization’s International Agency for Research on Cancer for rodents, it has evolved to include pathology of the major species (rats, mice, guinea pigs, nonhuman primates, pigs, dogs, fish, rabbits) used in medical research, safety assessment and mouse pathology. The collaborative effort today is driven by the needs of the regulatory agencies in multiple countries, and by needs of research involving genetically engineered animals, for “basic” research, and for more translational preclinical models of human disease. These efforts led to the establishment of an international rodent pathology nomenclature program. Since that time, multiple collaborations for standardization of laboratory animal pathology nomenclature and diagnostic criteria have been developed, and just a few are described herein. Recently, approaches to a nomenclature that is amenable to sophisticated computation have been made available and implemented for large-scale programs in functional genomics and ageing. Most terminologies continue to evolve as the science of human and veterinary pathology continues to develop, but standardization and successful implementation remain as critical for scientific communication, now as ever in the history of veterinary nosology.Government of Canada through Genome Canada and Ontario Genomics (OGI-051), Commission of the European Community QLRI-1999-CT-0320, the Ellison Medical Foundation, and the National Institutes of Health (CA34196, CA089713, and AG038070-05