SBML Level 3: an extensible format for the exchange and reuse of biological models.

Systems biology has experienced dramatic growth in the number, size, and complexity of computational models. To reproduce simulation results and reuse models, researchers must exchange unambiguous model descriptions. We review the latest edition of the Systems Biology Markup Language (SBML), a format designed for this purpose. A community of modelers and software authors developed SBML Level 3 over the past decade. Its modular form consists of a core suited to representing reaction-based models and packages that extend the core with features suited to other model types including constraint-based models, reaction-diffusion models, logical network models, and rule-based models. The format leverages two decades of SBML and a rich software ecosystem that transformed how systems biologists build and interact with models. More recently, the rise of multiscale models of whole cells and organs, and new data sources such as single-cell measurements and live imaging, has precipitated new ways of integrating data with models. We provide our perspectives on the challenges presented by these developments and how SBML Level 3 provides the foundation needed to support this evolution.

The Stem Cell Discovery Engine: an integrated repository and analysis system for cancer stem cell comparisons.

Mounting evidence suggests that malignant tumors are initiated and maintained by a subpopulation of cancerous cells with biological properties similar to those of normal stem cells. However, descriptions of stem-like gene and pathway signatures in cancers are inconsistent across experimental systems. Driven by a need to improve our understanding of molecular processes that are common and unique across cancer stem cells (CSCs), we have developed the Stem Cell Discovery Engine (SCDE)-an online database of curated CSC experiments coupled to the Galaxy analytical framework. The SCDE allows users to consistently describe, share and compare CSC data at the gene and pathway level. Our initial focus has been on carefully curating tissue and cancer stem cell-related experiments from blood, intestine and brain to create a high quality resource containing 53 public studies and 1098 assays. The experimental information is captured and stored in the multi-omics Investigation/Study/Assay (ISA-Tab) format and can be queried in the data repository. A linked Galaxy framework provides a comprehensive, flexible environment populated with novel tools for gene list comparisons against molecular signatures in GeneSigDB and MSigDB, curated experiments in the SCDE and pathways in WikiPathways. The SCDE is available at http://discovery.hsci.harvard.edu.

Evaluating the impacts of patient engagement on a national health research network: results of a case study of the Chronic Pain Network.

BACKGROUND: The Chronic Pain Network (CPN) is a pan-Canadian research network focused on innovating and improving the quality and delivery of pain prevention, assessment, management and research for all Canadians. An important focus of the CPN is to work in collaboration with patient partners. Patient partners, researchers and clinicians work together in all aspects of the research network including on funded research projects and in the governance of the Network. Given this focus, the CPN identified the importance of evaluating their patient engagement work to understand its functioning and impact. METHODS: The objective of this exploratory evaluation case study was to understand the impacts of patient engagement on the CPN. The CPN worked with an external evaluation team which established an arms-length approach to the evaluation. Interviews were conducted with CPN members, including patient partners, leadership, funded researchers and committee co-chairs, at three discrete time points to trace the evolution of the patient engagement program within the Network. Key Network documents were also collected and reviewed. Data were analyzed following each set of interviews using content analysis guided by the principles of constant comparison and qualitative description. A final round of analysis was conducted using the Engage with Impact Toolkit, an impact measurement framework, to identify impacts of engagement. RESULTS: Impacts of patient engagement were identified at the individual, network, funded research project and research community levels. These impacts were observed in the following areas: (1) building community; (2) developing knowledge, skills and resources; (3) increasing confidence; (4) influencing priorities and decisions; (5) enabling additional opportunities; (6) promoting culture change; and, (7) coping with experiences of living with chronic pain. CONCLUSIONS: While not without challenges, the patient engagement efforts of the CPN demonstrates the impact engaging patient partners can have on a national research network and related policy activities. Understanding the approaches to, and impacts of, patient engagement on health research networks can illuminate the value of having patient partners engaged in all aspects of a research network and should serve as encouragement to others who look to take on similar work.

The Chronic Pain Network (CPN) is one of a group of research networks that was funded by the Canadian Institutes of Health Research (CIHR) to support patient-oriented research in chronic diseases. From the beginning of its work, the CPN has included patients as partners. Patient partners are co-chairs of all Network governance committees, funded projects are required to include patient partners in their work and there is a committee dedicated to engagement, the Patient Engagement (PE) committee. The PE Committee determined that it was important to evaluate how the CPN was engaging with patient partners and collaborated with the Public and Patient Engagement Collaborative (PPEC) to evaluate this work. The PPEC, along with members of the PE Committee, identified understanding the impact of patient engagement as an important part of the evaluation. This paper provides a description of the impacts of patient engagement on the people who were involved in the CPN, on the CPN's work and way of being, and on the broader pain research community. Based on the results from three sets of interviews and review of Network documents, we share impacts identified in seven areas: (1) building community; (2) developing knowledge, skills and resources; (3) increasing confidence; (4) influencing priorities and decisions; (5) enabling additional opportunities; (6) promoting culture change; and, (7) coping with experiences of living with chronic pain. This research shows us the impact that engaging patient partners can have on a national research network, and the areas where greater focus could, perhaps, lead to even greater impacts in future networks.

ISA software suite: supporting standards-compliant experimental annotation and enabling curation at the community level.

UNLABELLED: The first open source software suite for experimentalists and curators that (i) assists in the annotation and local management of experimental metadata from high-throughput studies employing one or a combination of omics and other technologies; (ii) empowers users to uptake community-defined checklists and ontologies; and (iii) facilitates submission to international public repositories. AVAILABILITY AND IMPLEMENTATION: Software, documentation, case studies and implementations at http://www.isa-tools.org.

Out of the shadows: Chronic pain in Canadian Armed Forces veterans - Proceedings of a workshop at the 2019 Forum of the Canadian Institute for Military and Veteran Health Research.

This commentary summarizes proceedings of a workshop on chronic pain in military personnel and veterans (released personnel) at the Annual Forum of the Canadian Institute for Military and Veteran Health Research in Gatineau and Ottawa on October 22, 2019. The extent and impact of chronic pain among Canadian Armed Forces (CAF) veterans and their families is significant and has been underappreciated, largely due to limited disclosure by serving and veteran military personnel, stemming from a fear of stigmatization. Living with pain is seen as a fact of life in military cultures, something to be endured and not discussed. Though progress is being made in reducing the stigma of mental illness, the discourse on chronic pain remains censored. This workshop's goal was to bring the discussion of chronic pain out of the shadows in the search for ways to help veterans and active service personnel living with chronic pain. Many points of view were brought forward at this first national Canadian multidisciplinary gathering of researchers, veterans with lived experience, clinicians, and policymakers. A CAF member described his lived experience with constant chronic pain. Clinicians described aspects of chronic pain in military personnel and veterans whom they treat in their clinics. Dr. Ramesh Zacharias described the new Chronic Pain Center of Excellence for Canadian Veterans that will be established with funding from Veterans Affairs Canada. Dr. Norman Buckley highlighted collaboration with the existing Chronic Pain Network funded by the Canadian Institute for Health Research. Audience members identified a diverse variety of issues.

Ce commentaire résume les actes d'un atelier sur la douleur chronique chez le personnel militaire et les anciens combattants (personnel libéré) tenu dans le cadre du Forum annuel de l'Institut canadien de recherche sur la santé des militaires et des vétérans à Gatineau et Ottawa le 22 octobre 2019. L'étendue et l'effet de la douleur chronique chez les anciens combattants des Forces armées canadiennes (FAC) et leurs familles sont importantes et ont été sous-estimées, en grande partie en raison de la divulgation limitée par le personnel militaire en service et les anciens combattants, découlant de la peur de la stigmatisation. Le fait de vivre avec la douleur est considéré comme faisant partie de la vie dans les cultures militaires, quelque chose qu'il faut endurer et dont il ne faut pas discuter. Bien que des progrès aient été réalisés dans la réduction de la stigmatisation de la maladie mentale, le discours sur la douleur chronique continue d'être censuré. L'objectif de cet atelier était de faire sortir de l'ombre la discussion sur la douleur chronique afin de chercher des moyens d'aider les anciens combattants et le personnel de service actif vivant avec la douleur chronique. De nombreux points de vue ont été exprimés lors de cette première rencontre multidisciplinaire nationale canadienne réunissant des chercheurs, des anciens combattants ayant vécu l'expérience de la douleur chronique, des cliniciens et des décideurs. Un membre des FAC a décrit l'expérience de douleur chronique qu'il a vécue. Les cliniciens ont décrit les aspects de la douleur chronique chez le personnel militaire et les anciens combattants qu'ils traitent dans leurs cliniques. Le Dr Ramesh Zacharias a décrit le nouveau Centre d'excellence sur la douleur chronique pour les vétérans canadiens qui sera établi grâce au financement d'Anciens Combattants Canada. Le Dr Norman Buckley a souligné la collaboration avec le Réseau de douleur chronique existant financé par l'Institut canadien de la recherche en santé. Les membres de l'audience ont relevé divers problèmes.

Guidance on authorship with and acknowledgement of patient partners in patient-oriented research.

The Strategy for Patient-Oriented Research Chronic Pain Network was founded in 2016 and is a patient-oriented research network funded by the Canadian Institutes of Health Research. The Network incorporates patient partners throughout its governance and operations meaning that patient partners may contribute to research projects in ways that warrant scientific authorship as defined by the International Committee of Medical Journal Editors. The Network did a brief informal review of guidance on patient authorship in 2019, but could not find any practical documentation to guide its members on this topic. Note the term patient partner here refers to a patient (or caregiver or other person with lived experience) who is a partner or collaborator on a research team. This guidance does not address patients as participants in a research study. This guidance has been co-written by a group of researchers and patient partners of the Chronic Pain Network in an effort to address this gap. It is intended for both researchers and patient partner audiences. This guidance is meant to facilitate conversations between researchers and patient partners about authorship and/or acknowledgement regarding research projects on which they collaborate. While the overall principles of academic authorship and acknowledgement remain unchanged, nuances for interpreting these principles through the lens of patient engagement or patient-oriented research is provided. Teams that carry out patient-oriented research projects will require different preparation to empower all team members (researchers and patient partners) to discuss authorship and acknowledgement. To facilitate these conversations, we have included an overview of the scientific publishing process, explanation of some common terms, and sets of considerations are provided for both patient partners and researchers in determining the range of team member contribution from acknowledgement to authorship. Conversations about authorship can be difficult, even for established research teams. This guidance, and the resources discussed within it, are provided with the intention of making these conversations easier and more thoughtful.

Toward interoperable bioscience data.

To make full use of research data, the bioscience community needs to adopt technologies and reward mechanisms that support interoperability and promote the growth of an open 'data commoning' culture. Here we describe the prerequisites for data commoning and present an established and growing ecosystem of solutions using the shared 'Investigation-Study-Assay' framework to support that vision.

Phenotypical characterisation of the isolated norfolk island population focusing on epidemiological indicators of cardiovascular disease.

OBJECTIVES: Only 193 people from Pitcairn Island, all descended from 9 'Bounty' mutineers and 12 Tahitian women, moved to the uninhabited Norfolk Island in 1856. Our objective was to assess the population of Norfolk Island, several thousand km off the eastern coast of Australia, as a genetic isolate of potential use for cardiovascular disease (CVD) gene mapping. METHODS: A total of 602 participants, approximately two thirds of the island's present adult population, were characterized for a panel of CVD risk factors. Statistical power and heritability were calculated. RESULTS: Norfolk Islander's possess an increased prevalence of hypertension, obesity and multiple CVD risk factors when compared to outbred Caucasian populations. 64% of the study participants were descendents of the island's original founder population. Triglycerides, cholesterol, and blood pressures all had heritabilities above 0.2. CONCLUSIONS: The Norfolk Island population is a potentially useful genetic isolate for gene mapping studies aimed at identifying CVD risk factor quantitative trait loci (QTL).